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Breast and cervical cancer patients’ experience in Addis Ababa city, Ethiopia: A follow-up study protocol

Journal: BMJ Open ManuscriptFor ID peerbmjopen-2018-027034 review only Article Type: Protocol

Date Submitted by the 02-Oct-2018 Author:

Complete List of Authors: Gebremariam, Alem; Adigrat University, Public Health Addissie, Adamu; Addis Ababa University School of Public Health, Preventive Medicine Worku, Alemayehu; Addis Ababa University, School of Public Health Hirpa, Selamawit; Addis Ababa University School of Public Health Assefa, Mathewos ; Addis Ababa University School of Medicine, Oncology Pace, Lydia; Brigham and Women's Hospital, Boston, Massachusetts Kantelhardt, Eva; Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University, Halle, Germany Jemal, Ahmedin; American Cancer Society, Surveillance and Health Services Research

Breast Neoplasm, Uterine Cervical Neoplasm, Reported Outcome Keywords: http://bmjopen.bmj.com/ Measures

on September 25, 2021 by guest. Protected copyright.

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4 Breast and cervical cancer patients’ experience in Addis 5 6 7 Ababa city, Ethiopia: A follow-up study protocol 8 9 10 1,2 2 2 2 11 Alem Gebremariam *, Adamu Addissie , Alemayehu Worku Yalew , Selamawit Hirpa 12 13 Mathewos Assefa3, Lydia E. Pace4, Eva Johanna Kantelhardt5, Ahmedin Jemal6 14 15 1Department of Public Health, College of Medicine and Health Sciences, Adigrat University 16 For peer review only 17 18 Adigrat, Ethiopia 19 20 2School of Public Health, College of Health Sciences, Addis Ababa University, Addis Ababa, 21 22 Ethiopia 23 24 3 25 Department of Radiotherapy Center, School of Medicine, Addis Ababa University, Addis 26 27 Ababa, Ethiopia 28 29 4Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, 30 31 Boston, Massachusetts, USA 32 http://bmjopen.bmj.com/ 33 5 34 Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University, 35 36 Halle, Germany 37 38 6Surveillance and Health Services Research, American Cancer Society, Atlanta, Georgia, United 39

40 on September 25, 2021 by guest. Protected copyright. 41 States of America 42 43 44 * Corresponding Author 45 46 Abstract 47 48 49 50 Introduction: Cancer is an emerging public health problem in Ethiopia, with breast and cervical 51 52 cancers accounting for over half of all newly diagnosed cancers in women. Based on limited 53 54 published data, the majority of breast and cervical cancer patients are diagnosed at late stage of 55 56 57 58 1 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 the disease and most patients do not receive care consistent with global standards. However, little 4 5 6 is known about the health seeking behaviors, barriers to early detection and treatment, patient 7 8 reported outcomes, financial burden, and survival of breast and cervical cancer patients in the 9 10 country. Therefore, this study aims to document the experience of breast and cervical cancer 11 12 patients from recognition of symptoms to diagnosis, treatment, and survivorship/mortality in 13 14 15 Addis Ababa city, Ethiopia. 16 For peer review only 17 Methods and analysis: All consenting breast and cervical cancer patients diagnosed from 18 19 January 1, 2017 to June 30, 2018 who are residents of Addis Ababa City will be included in the 20 21 22 study and will be followed prospectively for two years. Pretested questionnaires will be 23 24 administered to patients by trained interviewers face-to-face or over the phone to collect 25 26 information about medical consultations after recognition of symptoms, health seeking 27 28 29 behaviors, treatment received, barriers to early detection and treatment, survivorship care, and 30 31 vital status. Information on treatments and clinical characteristics will be extracted from medical

32 http://bmjopen.bmj.com/ 33 records. Multivariable analysis will be employed to determine the contributions of independent 34 35 variables on the outcomes of interest. Hazard ratios with their corresponding 95% confidence 36 37 38 intervals will be calculated for time to event outcomes. Qualitative data will be analyzed using 39

40 thematic analysis. on September 25, 2021 by guest. Protected copyright. 41 42 Ethics and dissemination: This protocol is ethically approved by Addis Ababa University, 43 44 45 College of Health Science Institutional Review Board. Verbal informed consent will be obtained 46 47 from study participants prior to their enrollment. Results from this project will be disseminated 48 49 in international peer-reviewed journals and presented in relevant conferences. 50 51 52 53 54 55 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Keywords: Breast Neoplasm, Uterine Cervical Neoplasm, Patient Reported Outcome Measures, 4 5 6 Addis Ababa, Ethiopia 7 8 9 Strengths and limitations of this study 10 11 12 13 • To the best of our knowledge, this study is the first population based prospective follow- 14 15 up study in Ethiopia to determine the experience of breast and cervical cancer patients 16 For peer review only 17 18 from the first symptom recognition through the course of survivorship care using rigorous 19 20 mixed methods. 21 22 • Being prospective follow-up study design, allows us to test the temporal relationship 23 24 25 between patient and or provider delay and survival of breast and cervical cancer patients. 26 27 • Our study will try to capture all of the incident cases of the city so that generalization 28 29 about breast and cervical cancer patients in the city will be possible latter. 30 31

32 • The study will identify gaps and barriers to receipt of cancer care in Addis Ababa from a http://bmjopen.bmj.com/ 33 34 patient perspective, which will inform public health policies and clinical guidelines for 35 36 early detection and improving the quality of cancer care in Addis Ababa and other parts 37 38 39 of the country.

40 on September 25, 2021 by guest. Protected copyright. 41 • It will also provide patient narratives and quantitative evidence to support efforts to 42 43 increase public awareness and advocate for increased resources to reduce suffering and 44 45 death from cancer in Ethiopia. 46 47 48 49 50 51 52 53 54 55 56 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Introduction 4 5 6 Breast and cervical cancers are the most commonly diagnosed cancers and the leading causes of 7 8 cancer death among women in Ethiopia and in other parts of sub-Saharan Africa [1-3], 9 10 11 accounting for about half of all cancer cases and deaths [4]. These cancers have significant 12 13 public health and societal implications not only because they represent more than half of all 14 15 cancer cases in women but also because they most frequently occur in young or middle age [5, 6] 16 For peer review only 17 18 when patients are in the workforce, raising children, and supporting other family members. 19 20 21 The morbidity and mortality associated with breast and cervical cancer can be mitigated through 22 23 early detection and receipt of evidence-based, high quality care [7]. However, based on limited 24 25 data, a substantial proportion of breast and cervical cancer patients in Ethiopia present with 26 27 28 advanced-stage disease. For instance, about 71% of the breast cancer cases [6] and 84% cervical 29 30 cancer cases [5] in Ethiopia were diagnosed at advanced stage largely because of patient delays 31 32 in seeking medical care after recognition of symptoms and provider/health systems delay in http://bmjopen.bmj.com/ 33 34 35 referral of patients to cancer treatment centers [8, 9]. Further, most breast and cervical cancer 36 37 patients in the country do not receive treatments consistent with the global standard of care [3]. 38 39

40 In addition to early detection and receipt of standard treatments, survivorship care is an on September 25, 2021 by guest. Protected copyright. 41 42 important component of high quality of care across the cancer continuum. This could be assessed 43 44 45 through Patient Reported Outcomes (PROs) as well as physician ratings of patients’ wellbeing 46 47 [10], though PROs are found to be better predictors of patients survival and are thought to be 48 49 more useful for making clinical decision about patient management [10, 11]. There is, however, 50 51 52 limited information on barriers to early detection and receipt of and completion of treatment and 53 54 55 56 57 58 4 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 patient reported outcomes among breast and cervical cancer patients in Ethiopia to guide public 4 5 6 health policies and patient management [12]. 7 8 9 Previous studies from Ethiopia have reported limited knowledge about breast and cervical 10 11 cancer, including about prevention, early detection, and treatment, among healthcare 12 13 professionals [13-16] and the general population [17-27]. This limited awareness likely 14 15 16 contributes to the highFor proportion peer of disease review detected at advanced only stage in the country [5, 6]. 17 18 Notably, there are also studies conducted on breast and cervical cancer patients [5, 6, 8, 9, 28- 19 20 33]. Two of the studies [8, 28] examined patient or provider delay among breast cancer patients 21 22 23 in Ethiopia and found long waiting times to initiate medical consultation (average about 18 24 25 months). Similarly, Tadesse reported that about 30% (56/198 patient) of cervical cancer patients 26 27 visited 3 or more health facilities before being referred to Tikur Anbessa Specialized Hospital 28 29 30 (TASH) for cancer-directed treatment and 20% (46) of the patients waited for more than 6 31

32 months from first health care visit before they were first seen at TASH [34]. http://bmjopen.bmj.com/ 33 34 35 The aforementioned studies, however, were limited because of small sample sizes [8, 28], and 36 37 reliance on data from chart review [6, 28-30] and data were collected from only one hospital, 38 39

40 TASH, which houses the only radiotherapy center in the country [5, 6, 8, 28-30, 32]. These all on September 25, 2021 by guest. Protected copyright. 41 42 could make them prone to incompleteness and limit their generalizability to elsewhere in 43 44 Ethiopia. Moreover, none of the studies examined the factors contributing to patient and provider 45 46 47 delays, patient reported outcomes, the relationship between patient/provider delay and stage at 48 49 diagnosis as well as its effect on the survival of breast or cervical cancer patients in Ethiopia. To 50 51 help address this information gap, we have established a population-based, prospective follow-up 52 53 54 study of newly diagnosed breast and cervical cancer patients in Addis Ababa, capital city of 55 56 57 58 5 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Ethiopia. This paper describes the protocol of the study, the first population-based prospective 4 5 6 study on cancer patients’ experience in the country and perhaps in Africa. 7 8 9 Methods 10 11 12 13 Aim of the study 14 15 • To estimate the duration of patient, diagnostic and treatment initiation intervals for breast 16 For peer review only 17 and cervical cancer patients 18 19 20 • To examine the association between patient/diagnostic interval and stage at diagnosis 21 22 • To describe treatment patterns and adherence by socio-demographic factors 23 24 25 • To determine patient reported outcomes (levels of fatigue, pain, sleep disorder, and 26 27 depression) 28 29 • To estimate the financial burden of breast and cervical cancer on patients and their families 30 31

32 • To document survivorship care (e.g., surveillance for recurrence and late effects of http://bmjopen.bmj.com/ 33 34 treatment) 35 36 • To estimate two-year survival rates and their associations with patient, diagnostic and 37 38 39 treatment initiation intervals, receipt of treatment, socio-demographic factors, financial

40 on September 25, 2021 by guest. Protected copyright. 41 burden, and other patient reported outcomes. 42 43 44 Study setting 45 46 47 This study will be conducted in the Addis Ababa, which has a population of about 3.5 million 48 49 50 [35]. The city is served by 6 public and 36 private hospitals, 53 public health centers, and 51 52 around 700 private clinics [36]. A population-based cancer registry has been in place since 2011 53 54 in Addis Ababa, with incident cases collected from 20 health facilities including referral 55 56 57 58 6 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 hospitals, higher clinics, and diagnostic centers [4]. Our study will recruit all female breast and 4 5 6 cervical cancer patients aged >18 years diagnosed from January 1, 2017 – June 30, 2018 in 8 7 8 major health facilities, which capture more than 90% of all female breast and cervical cancer 9 10 cases reported to the cancer registry. 11 12 13 Study designs and sample size 14 15 16 For peer review only 17 The study design is a prospective follow-up study, using mixed methods (both quantitative and 18 19 qualitative). The quantitative component involves both cross sectional and prospective follow-up 20 21 study designs, while the qualitative study is phenomenological study. The latter study design will 22 23 24 help to understand the breast and cervical cancer patients’ experience of their life before and 25 26 after diagnosis, and during the course of treatment [11]. We expect to recruit about 450 breast 27 28 and 250 cervical cancer patients, based on the number of breast and cervical cases recorded each 29 30 31 year in the city over the past two years [37], and they will be followed for two years.

32 http://bmjopen.bmj.com/ 33 34 Data collection tools and techniques 35 36 37 Three data collection tools will be used to address the objectives of the project: an interviewer 38 39 administered questionnaire, an in-depth interview guide, and a medical record data extraction

40 on September 25, 2021 by guest. Protected copyright. 41 tool. The tools are being developed in English, translated into Amharic, and back translated into 42 43 44 English. The Amharic version will be used for conducting the interview. 45 46 47 The interviewer administered questionnaire is organized into two parts. The first part of the 48 49 questionnaire addresses participants’ socio-demographic characteristics, medical history, and 50 51 52 pathway to diagnosis which is adopted from a questionnaire for a similar study in Rwanda [38]. 53 54 In addition, this first phase of questionnaire also includes questions about patient reported 55 56 57 58 7 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 outcomes. This questionnaire will be administered face to face by trained interviewers at the time 4 5 6 of participants’ recruitment. 7 8 9 The second tool investigates receipt of and adherence to treatments, financial hardship, and vital 10 11 status. The questions are adapted from different standardized tools developed by the American 12 13 Cancer Society [39], National Cancer Institute [40, 41], the Agency for Healthcare Research and 14 15 16 Quality, the CentersFor for Disease peer Control reviewand Prevention of onlythe U.S. Department of Health and 17 18 Human Services [42]. Patients will be interviewed about one year after their cancer diagnosis by 19 20 a trained interviewer, in person when possible and by telephone otherwise. Phone calls will be 21 22 23 made at least three times at different times of the day, evening and weekends to increase the 24 25 response rate of the study participants. Those patients who are not interviewed through this 26 27 mechanism, will be considered as lost to follow-up [43]. For patients who died or are too ill to be 28 29 30 interviewed, a surrogate (relative or household member) familiar with their cancer care will be 31

32 interviewed. http://bmjopen.bmj.com/ 33 34 35 The medical record data extraction tool will be used to collect information about date of 36 37 diagnosis, tumor characteristics (e.g., stage at diagnosis, metastasis and recurrence), initiation 38 39

40 and completion of treatments, vital status from paper medical records at the 8 participating on September 25, 2021 by guest. Protected copyright. 41 42 facilities. Medical record review will occur at about one and two years after diagnosis. 43 44 45 In addition to the interviewer-administered questionnaire and extraction tool, a semi-structured 46 47 48 interview guide will be developed and used for in-depth interviews. This instrument will include 49 50 patients’ knowledge and perception of breast and cervical cancer, and their experience from the 51 52 recognition of first symptom of the disease to diagnosis and treatment. 53 54 55 56 57 58 8 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Term definitions and measurements 4 5 6 Waiting time for assessing patient interval will be computed by subtracting the date when the 7 8 first symptom for breast or cervical cancer was noticed from the date of first presentation to 9 10 11 Health Care Provider (HCP) for the concern of the symptoms [44]. Patients that waited >3 12 13 months before consulting health care provider will be considered as delayed “Yes”, and “No” if 14 15 they sought care within 3 months of the first symptom recognized [45-47]. 16 For peer review only 17 18 19 Diagnostic interval in diagnosis of breast or cervical cancer will be computed by subtracting the 20 21 date of first contact with HCP from date of confirmation of breast or cervical cancer. Treatment 22 23 interval will be computed by subtracting the date of confirmation from the date of treatment 24 25 26 initiation. Total interval will be computed by subtracting the date of first time recognition of 27 28 symptom from the date of treatment initiation [44]. 29 30 31 If the participants are unable to recall the exact date of first symptom recognized or date of first

32 http://bmjopen.bmj.com/ 33 medical consultation made, they will be asked to provide a month or month range and year. If 34 35 th 36 they provided a month, the date will be estimated as the 15 of that month; if they provided a 37 38 month range, the estimated date will be the midpoint between the 15th of those months. If 39 40 patients were only able to provide the year, the estimated date will be June 30th of that year [38]. on September 25, 2021 by guest. Protected copyright. 41 42 43 44 Stage at diagnosis will be grouped into early stage (patient presented with clinical stage II and 45 46 below) and advanced stage (patients presented with clinical stage III or above) diseases [48, 49]. 47 48 49 Disease Free Survival (DFS) will be computed for stage I-III cases who are treated with curative 50 51 52 intention from the date of primary treatment to the date of local, contra-lateral or distant 53 54 recurrence or death from breast or cervical cancer. Distant DFS will be computed from the date 55 56 57 58 9 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 of primary treatment to the date of distant metastasis or death from breast or cervical cancer. 4 5 6 Overall Survival (OS) will be computed from the date of diagnosis to the date of death. For 7 8 patients who remained alive and disease-free, data will be censored at the date of the last contact 9 10 [50]. 11 12 13 14 Data quality assurance mechanism 15 16 Several measures willFor be taken peer to maintain review the quality of the onlyresearch starting from designing the 17 18 19 tool to data analysis and interpretations of the findings. Tool translation and back translation will 20 21 be done to ensure the consistency of the survey tools. In addition to this, the questionnaire will 22 23 be pre-tested and relevant corrections will be made. 24 25 26 Data collectors and supervisor will be recruited based on the level of education, ability to 27 28 29 communicate using the working language, and experience on data collection. Moreover, they 30 31 will be trained on the objectives of the study, data collection tools, interviewing techniques, and

32 http://bmjopen.bmj.com/ 33 ethical procedures before the implementation of the project. 34 35 36 In addition to the training of the data collectors, they will be supervised by the supervisor and 37 38 39 principal investigators. Filled questionnaires will be checked for their completeness and

40 on September 25, 2021 by guest. Protected copyright. 41 consistency on daily base by the supervisor. Biweekly meetings will be held with the supervisor 42 43 of the data collectors and the investigators to discuss and solve any problems encountered in the 44 45 46 data collection process. 47 48 49 To minimize errors during data entry, templates will be developed using Epi-Info using check 50 51 codes. After the entry is completed, the sample of the questionnaires will be rechecked for 52 53 correctness against the raw data, and necessary corrections will be made before the analysis. 54 55 56 57 58 10 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 To maintain the trustworthiness of the qualitative data, interviews will be collected, transcribed 4 5 6 and analyzed by individuals experienced in qualitative data collection and analysis. All 7 8 interviews will be tape recorded to grasp all the points during the interview. Moreover, data will 9 10 be transcribed by the data collectors on a daily base to maintain the consistency and the context 11 12 of the discussion, and checked for errors by listening back to the audio-recording and reading the 13 14 15 transcripts simultaneously. Finally, the transcribed data will be coded using NVivo software to 16 For peer review only 17 facilitate the reduction of the qualitative data without missing the central idea. 18 19 20 21 Data management analysis plan 22 23 Data will be entered and cleaned by Epi-Info 3.5.1 version, and exported into Stata version 13 24 25 26 for analysis. First, descriptive analyses will be carried out for each of the variables. Second, 27 28 bivariate analyses will be done to select independent variables to the multivariable analyses. 29 30 Odds Ratio (OR) with its 95% Confidence Interval (CI) will be calculated for each independent 31 32 variable. Finally, variables reported as having an impact on delay, and survival in the literature, http://bmjopen.bmj.com/ 33 34 35 and those variables which show significant association (P<0.25) with the dependent variable in 36 37 the bivariate analysis will be entered into the multivariable logistic regression model to identify 38 39 their independent effects. Then, statistical significance will be declared at P value < 0.05. 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 We will also compute hazard ratio (HR) for time to event outcomes, with its corresponding 95% 44 45 CIs, and associated p-values. Cox’s proportional hazard model will be used to identify factors 46 47 associated with the survival of the patients. Overall survival will be estimated using the Kaplan- 48 49 Meier method and compared using the log-rank test. The proportional hazards assumption will 50 51 52 be checked using graphical method and goodness of fit test. Multivariable Cox regression 53 54 55 56 57 58 11 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 12 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 analysis will be used to estimate the hazard of all-cause mortality (HR) associated with the pre- 4 5 6 selected various prognostic factors that we are studying. 7 8 9 For the qualitative data, audio data will be transcribed verbatim into Microsoft Word files and 10 11 translated from the local language to English. Before the analysis, the text will be read through 12 13 several times to obtain a sense of the whole and familiarize with the data. Then word transcript 14 15 16 of the data will be Forimported peerinto NVivo softwarereview version 11only [51] and coded line by line. The 17 18 codes will be compared based on differences and similarities and sorted into categories, and 19 20 categories will be grouped in themes. Finally, the result will be presented in them and 21 22 triangulated with the quantitative result during write up. 23 24 25 26 Ethical considerations and result dissemination 27 28 29 Ethical clearance has been secured from the Institutional Review Board (IRB) of Addis Ababa 30 31 University, College of Health Science with the registration number of 018/17/SPH. We have

32 http://bmjopen.bmj.com/ 33 conducted rapid ethical assessment to design the consent document and the consent process. In 34 35 36 addition to this, ethical issues have been discussed and given emphasis during the training of data 37 38 collectors and supervisor. 39 40 Eligible patients will be verbally informed, by trained research personnel, regarding the nature on September 25, 2021 by guest. Protected copyright. 41 42 43 and purpose of the study, and given time to decide whether or not to participate in the follow-up 44 45 study. Verbal informed consent will be obtained from study participants prior to their enrollment. 46 47 Enrollment will be fully based on the voluntary participation of the study participants and 48 49 respondents who are interested to avoid specific questions or discontinue the interview will be 50 51 52 allowed to do so. 53 54 55 56 57 58 12 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 13 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Confidentiality of any information related to the patient and her clinical history will be 4 5 6 maintained by keeping both the hard copy and softcopy of every collected data in a locked 7 8 cabinet and password secured computer. 9 10 We intend to present the results of our follow-up study via scientific publications in peer- 11 12 reviewed journals as well as through presentation to stakeholders including the public, patients, 13 14 15 clinicians and policymakers. 16 For peer review only 17 18 Information gathered from this study will inform clinical guidelines and public health policies 19 20 improve the quality of cancer patients’ care delivered in the city, as well as other parts of the 21 22 23 country. It will also be used to produce fact-based materials to develop "stories" that illustrate the 24 25 compelling need for increased resources to reduce suffering and death from cancer. Experience 26 27 of the survivors will become available and presented to the public to enrich awareness campaigns 28 29 30 and show that cancer is not a death sentence [52] but patients can as well be cured. Furthermore, 31

32 this collaborative project will provide research collaboration opportunities for several graduate http://bmjopen.bmj.com/ 33 34 students, residents, and junior and senior faculty members of Addis Ababa University and in 35 36 doing so will enhance the capacity of the university in conducting cancer care delivery and 37 38 39 epidemiologic research.

40 on September 25, 2021 by guest. Protected copyright. 41 42 References 43 44 45 1. Torre LA, Islami F, Siegel RL, M.Ward E, Jemal A. Global Cancer in Women: Burden and 46 47 Trends. Cancer Epidemiol Biomarkers Prev; 26(4). 2017;26(4). 48 49 2. Kantelhardt EJ, Gizaw M, Getachew S, Ayele W, Gebert HC, Unverzagt S, et al. A Review 50 51 on Breast Cancer Care in Africa. Breast Care. 2015;10:364-70. 52 3. Jemal A, Bray F, Forman D, O’Brien M, Ferlay J, Center M, et al. Cancer Burden in Africa 53 54 and Opportunities for Prevention. Cancer. 2012;118:4372-84. 55 56 57 58 13 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4. Timotewos G, Solomon A, Mathewos A, Addissie A, Bogale S, Wondemagegnehu T, et al. 4 5 First data from a population based cancer registry in Ethiopia. Cancer epidemiology. 2018 6 7 Feb 1;53:93-8. PubMed PMID: 29414637. Epub 2018/02/08. eng. 8 5. Kantelhardt EJ, Moelle U, Begoihn M, Addissie A, Trocchi P, Yonas B, et al. Cervical 9 10 Cancer in Ethiopia: Survival of 1,059 Patients Who Received Oncologic Therapy. The 11 12 Oncologist. 2014;19:727-34. 13 14 6. Kantelhardt E.J, Zerche P, Mathewos A, Trocchi P, Addissie A, Aynalem A, et al. Breast 15 cancer survival in Ethiopia: A cohort study of 1,070 women. Int J Cancer 2013 (135):702–9. 16 For peer review only 17 7. World Health Organization. Global status report on noncommunicable diseases 2010. 18 19 Geneva, Switzerland: 2011. 20 21 8. Dye TD, Bogale S, Hobden C, Tilahun Y, Deressa T, Reeler A. Experience of Initial 22 Symptoms of Breast Cancer and Triggers for Action in Ethiopia. Hindawi Publishing 23 24 Corporation, International Journal of Breast Cancer. 2012;2012:1-5. 25 26 9. Dye TDV, Bogale S, Hobden C, Tilahun Y, Hechter V, Deressa T, et al. A mixed-method 27 assessment of beliefs and practice around breast cancer in Ethiopia: Implications for public 28 29 health programming and cancer control. Global Public Health, An International Journal for 30 31 Research, Policy and Practice. 2011;6(7):719-31.

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32 http://bmjopen.bmj.com/ 33 Knowledge and Awareness of Cervical Cancer among HIV-Infected Women in Ethiopia. 34 Obstetrics and gynecology international. 2016;2016:1274734. PubMed PMID: 27867397. 35 36 Pubmed Central PMCID: PMC5102747. Epub 2016/11/22. eng. 37 38 21. Aweke YH, Ayanto SY, Ersado TL. Knowledge, attitude and practice for cervical cancer 39 prevention and control among women of childbearing age in Hossana Town, Hadiya zone, 40 on September 25, 2021 by guest. Protected copyright. 41 Southern Ethiopia: Community-based cross-sectional study. PloS one. 2017;12(7):e0181415. 42 43 PubMed PMID: 28742851. Pubmed Central PMCID: PMC5526548. Epub 2017/07/26. eng. 44 45 22. Tefera F, Mitiku I. Uptake of Cervical Cancer Screening and Associated Factors Among 15- 46 49-Year-Old Women in Dessie Town, Northeast Ethiopia. Journal of cancer education : the 47 48 official journal of the American Association for Cancer Education. 2016 Apr 13. PubMed 49 50 PMID: 27075197. Epub 2016/04/15. eng. 51 52 23. Mitiku I, Tefera F. Knowledge about Cervical Cancer and Associated Factors among 15-49 53 Year Old Women in Dessie Town, Northeast Ethiopia. PloS one. 2016;11(9):e0163136. 54 55 PubMed PMID: 27690311. Pubmed Central PMCID: PMC5045174. Epub 2016/10/01. eng. 56 57 58 15 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 24. Getahun F, Mazengia F, Abuhay M, Birhanu Z. Comprehensive knowledge about cervical 4 5 cancer is low among women in Northwest Ethiopia. BMC cancer. 2013 Jan 02;13:2. PubMed 6 7 PMID: 23282173. Pubmed Central PMCID: PMC3559275. Epub 2013/01/04. eng. 8 25. Bayu H, Berhe Y, Mulat A, Alemu A. Cervical Cancer Screening Service Uptake and 9 10 Associated Factors among Age Eligible Women in Mekelle Zone, Northern Ethiopia, 2015: 11 12 A Community Based Study Using Health Belief Model. PloS one. 2016;11(3):e0149908. 13 14 PubMed PMID: 26963098. Pubmed Central PMCID: PMC4786115. Epub 2016/03/11. eng. 15 26. Birhanu Z, Abdissa A, Belachew T, Deribew A, Segni H, Tsu V, et al. Health seeking 16 For peer review only 17 behavior for cervical cancer in Ethiopia: a qualitative study. International journal for equity 18 19 in health. 2012 Dec 29;11:83. PubMed PMID: 23273140. Pubmed Central PMCID: 20 21 PMC3544623. Epub 2013/01/01. eng. 22 27. Belete N, Tsige Y, Mellie H. Willingness and acceptability of cervical cancer screening 23 24 among women living with HIV/AIDS in Addis Ababa, Ethiopia: a cross sectional study. 25 26 Gynecologic oncology research and practice. 2015;2:6. PubMed PMID: 27231566. Pubmed 27 Central PMCID: PMC4881166. Epub 2015/01/01. eng. 28 29 28. Ersumo T. Breast Cancer in an Ethiopian Population, Addis Ababa. East and Central African 30 31 Journal of Surgery 2006;11(1).

32 http://bmjopen.bmj.com/ 33 29. Abate SM, Yilma Z, Assefa M, Tigeneh W. Trends of Breast Cancer in Ethiopia. Int J 34 Cancer Res Mol Mech. 2016;2(1). 35 36 30. Kantelhardt EJ, Assefa M, Abreha A, Tigeneh W, Jemal A, Vetter M, et al. The prevalence 37 38 of estrogen receptor-negative breast cancer in Ethiopia. BMC Cancer. 2014;14(895). 39 31. Hailu A, Mariam DH. Patient side cost and its predictors for cervical cancer in Ethiopia: a 40 on September 25, 2021 by guest. Protected copyright. 41 cross sectional hospital based study. BMC Cancer. 2013;13(69). 42 43 32. Dye TD, Bogale S, Hobden C, Tilahun Y, Hechter V, Deressa T, et al. Complex Care 44 45 Systems in Developing Countries: Breast Cancer Patient Navigation in Ethiopia. American 46 Cancer Society. 2010;116:577-85. 47 48 33. Gizaw M, Addissie A, Getachew S, Ayele W, Mitiku I, Moelle U, et al. Cervical cancer 49 50 patients presentation and survival in the only oncology referral hospital, Ethiopia: a 51 52 retrospective cohort study. Infect Agent Cancer. 2017;12:61. PubMed PMID: 29213299. 53 Pubmed Central PMCID: 5708091. Epub 2017/12/08. eng. 54 55 56 57 58 16 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 34. Tadesse SK. Socio-economic and cultural vulnerabilities to cervical cancer and challenges 4 5 faced by patients attending care at Tikur Anbessa Hospital: a cross sectional and qualitative 6 7 study. BMC Women's Health. 2015;15(75). 8 35. Federal Democratic Repeblic of Ethiopia Centeral statistics Agency. Population Projection of 9 10 Ethiopia for All Regions At Wereda Level from 2014 – 2017 assessed on Nov. 23, 2016 from 11 12 www.csa.gov.et/. 2013. 13 14 36. City Government of Addis Ababa Bureau of Finance and Economic Development. Socio- 15 Economic Profile of Addis Ababa For the Year 2004 E.C/2011/12G.C. Accessed on Nov. 26, 16 For peer review only 17 2016 from 18 19 www.aabofed.gov.et/Documents/Addis%20Ababa%20Profile%20%202004%20E.pdf. 2013. 20 21 37. African Cancer Regisrty Network. Addis Ababa population Based cancer registery. Addis 22 Ababa City Cancer Registry - African Cancer Registry Network 23 24 afcrn.org/membership/members/100-Addisababa [cited 2016 June 27]. 25 26 38. Pace LE, Tharcissempunga, Hategekimana V, Dusengimana J-MV, Habineza H, Bigirimana 27 JB, et al. Delays in Breast Cancer PresentationandDiagnosis at TwoRural Cancer Referral 28 29 Centers in Rwanda. The Oncologist. 2015;20:780-8. 30 31 39. American Cancer Society. National Quality of life survey.

32 http://bmjopen.bmj.com/ 33 40. National Cancer Instutite and Northern California. Assessment of Patients’ Experience of 34 Cancer Care (APECC) Study. 35 36 41. National Cancer Instutite U.S. Department of Health and Human Services National Institutes 37 38 of Health. Adolecent and Young Adult Health Outcome and Patient Experiance. Follow-up 39 survey. 40 on September 25, 2021 by guest. Protected copyright. 41 42. The Agency for Healthcare Research and Quality and The Centers for Disease Control and 42 43 Prevention of the U.S. Department of Health and Human Services. Medical Expenditure 44 45 Survey. Your Experiences with Cancer. 46 43. Harlan LC, Lynch CF, Keegan THM, Hamilton AS, Wu X-C, Kato I, et al. Recruitment and 47 48 follow-up of adolescent and young adult cancer survivors: the AYA HOPE Study. J Cancer 49 50 Surviv. 2011;5:305-14. 51 52 44. Weller D, Vedsted P, Rubin G, Walter FM, Emery J, Scott S, et al. The Aarhus statement: 53 improving design and reporting of studies on early cancer diagnosis. Br J Cancer. 2012 Mar 54 55 56 57 58 17 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 19 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 27;106(7):1262-7. PubMed PMID: 22415239. Pubmed Central PMCID: 3314787. Epub 4 5 2012/03/15. eng. 6 7 45. Sharma K, Costas A, Damuse R, Hamiltong-Pierre J, Pyda J, Ong CT, et al. The Haiti Breast 8 Cancer Initiative: Initial Findings and Analysis of Barriers-to-Care Delaying Patient 9 10 Presentation. Hindawi Publishing Corporation: Journal of Oncology. 2013;2013:6. 11 12 46. Ramirez AJ, Westcombe AM, Burgess CC, Sutton S, Littlejohns P, Richards MA. Factors 13 14 predicting delayed presentation of symptomatic breast cancer: a systematic review. Lancet. 15 1999;353:1127-31. 16 For peer review only 17 47. Sharma K, Costas A, Shulman LN, G.Meara J. A Systematic Review of Barriers to Breast 18 19 Cancer Care in Developing Countries Resulting in Delayed Patient Presentation. Hindawi 20 21 Publishing Corporation Journal of Oncology. 2012;2012:8. 22 48. Edge SB. AJCC cancer staging manual. 7th ed. . New York: Springer; 2010. 23 24 49. Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J 25 26 Gynaecol Obstet. 2009 May;105(2):107-8. PubMed PMID: 19342051. Epub 2009/04/04. 27 eng. 28 29 50. Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, et al. Proposal 30 31 for standardized definitions for efficacy end points in adjuvant breast cancer trials: the

32 http://bmjopen.bmj.com/ 33 STEEP system. J Clin Oncol. 2007 May 20;25(15):2127-32. PubMed PMID: 17513820. 34 Epub 2007/05/22. eng. 35 36 51. Hamunyela RH, Serafin AM, Akudugu JM. Strong synergism between small molecule 37 38 inhibitors of HER2, PI3K, mTOR and Bcl-2 in human breast cancer cells. Toxicology in 39 vitro : an international journal published in association with BIBRA. 2017 Feb;38:117-23. 40 on September 25, 2021 by guest. Protected copyright. 41 PubMed PMID: 27737796. Epub 2016/10/21. eng. 42 43 52. Azubuike SO, Muirhead C, Hayes L, McNally R. Rising global burden of breast cancer: the 44 45 case of sub-Saharan Africa (with emphasis on Nigeria) and implications for regional 46 47 48 development: a review. World Journal of Surgical Oncology. 2018 March 22;16(1):63. 49 50 51 52 Authors’ contributions 53 54 55 56 57 58 18 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 AG carried out the conception and designing the study, and wrote the manuscript. AA, AWY, 4 5 6 SH, MA, EJK, LEP, and AJ critically reviewed throughout the course of designing the study, 7 8 reviewing and editing the final draft of the manuscript. All authors read and approved the final 9 10 draft of the manuscript. 11 12 13 Funding 14 15 16 This project is supportedFor by thepeer Intramural review Research Department only of the American Cancer 17 18 Society. 19 20 21 22 Competing interests 23 24 The authors declare that they have no competing interests. 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 19 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from

Breast and cervical cancer patients’ experience in Addis Ababa city, Ethiopia: A follow-up study protocol

Journal: BMJ Open ManuscriptFor ID peerbmjopen-2018-027034.R1 review only Article Type: Protocol

Date Submitted by the 18-Jan-2019 Author:

Complete List of Authors: Gebremariam, Alem; Adigrat University, Public Health Addissie, Adamu; Addis Ababa University School of Public Health, Preventive Medicine Worku, Alemayehu; Addis Ababa University, School of Public Health Hirpa, Selamawit; Addis Ababa University School of Public Health Assefa, Mathewos ; Addis Ababa University School of Medicine, Oncology Pace, Lydia; Brigham and Women's Hospital, Boston, Massachusetts Kantelhardt, Eva; Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University, Halle, Germany Jemal, Ahmedin; American Cancer Society, Surveillance and Health Services Research

Primary Subject Oncology http://bmjopen.bmj.com/ Heading:

Secondary Subject Heading: Oncology, Public health, Epidemiology

Breast Neoplasm, Uterine Cervical Neoplasm, Reported Outcome Keywords: Measures, Addis Ababa, Ethiopia

on September 25, 2021 by guest. Protected copyright.

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4 Breast and cervical cancer patients’ experience in Addis 5 6 7 Ababa city, Ethiopia: A follow-up study protocol 8 9 10 11 Alem Gebremariam1,2*, Adamu Addissie2, Alemayehu Worku Yalew2, Selamawit Hirpa2 12 13 Mathewos Assefa3, Lydia E. Pace4, Eva Johanna Kantelhardt5, Ahmedin Jemal6 14 15 1Department of Public Health, College of Medicine and Health Sciences, Adigrat University 16 For peer review only 17 18 Adigrat, Ethiopia 19 20 2School of Public Health, College of Health Sciences, Addis Ababa University, Addis Ababa, 21 22 Ethiopia 23 24 3 25 Department of Radiotherapy Center, School of Medicine, Addis Ababa University, Addis 26 27 Ababa, Ethiopia 28 29 4Brigham and Women's Hospital, Boston, Massachusetts, USA 30 31 5Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University, 32 http://bmjopen.bmj.com/ 33 34 Halle, Germany 35 36 6Surveillance and Health Services Research, American Cancer Society, Atlanta, Georgia, United 37 38 States of America 39

40 on September 25, 2021 by guest. Protected copyright. 41 * Corresponding Author: Alem Gebremariam, BSc, MPH 42 43 44 Addis Ababa University, Ethiopia 45 46 Email: [email protected]; Tel: +251-910352915 47 48 49 Word count=3997 (excluding title page, abstract, Strengths and limitations of this study 50 51 References) 52 53 54 55 56 57 58 1 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 ABSTRACT 4 5 6 7 Introduction: Cancer is an emerging public health problem in Ethiopia, with breast and cervical 8 9 cancers accounting for over half of all newly diagnosed cancers in women. The majority of women 10 11 with breast and cervical cancer are diagnosed at late stage of the disease and most patients do not 12 13 14 receive care consistent with global standards. However, little is known about the health seeking 15 16 behaviors, barriers toFor early detection peer and treatment,review patient reportedonly outcomes, financial burden, 17 18 and survival of women with breast and cervical cancer in the country. Therefore, this study aims 19 20 21 to document the experience of women with breast and cervical cancer from recognition of 22 23 symptoms to diagnosis, treatment, and survivorship/mortality in Addis Ababa city, Ethiopia. 24 25 Methods and analysis: A prospective follow-up study using mixed methods (both quantitative 26 27 28 and qualitative) will be employed. All women newly diagnosed with breast and cervical cancer 29 30 from January 1, 2017 to June 30, 2018 in Addis Ababa will be included in the study. Interviewer 31

32 administered questionnaires will be used to collect information about medical consultations after http://bmjopen.bmj.com/ 33 34 recognition of symptoms, health seeking behaviors, treatment received, barriers to early detection 35 36 37 and treatment, and survivorship care. In-depth interview will be conducted on purposefully 38 39 selected women with breast and cervical cancer. The primary outcomes of the study are time

40 on September 25, 2021 by guest. Protected copyright. 41 intervals (patient and diagnostic waiting times), stage at diagnosis, and survival. Multivariable 42 43 44 analysis will be employed to determine the contributions of independent variables on the outcomes 45 46 of interest. Hazard ratios with 95% confidence intervals will be calculated for time to event 47 48 outcomes. Qualitative data will be analyzed using thematic analysis. 49 50 51 Ethics and dissemination: This protocol is ethically approved by Institutional Review Board of 52 53 Addis Ababa University. Verbal informed consent will be obtained from study participants. 54 55 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Results will be disseminated in international peer-reviewed journals and presented in relevant 4 5 6 conferences. 7 8 9 Keywords: Breast Neoplasm, Uterine Cervical Neoplasm, Patient Reported Outcome Measures, 10 11 Addis Ababa, Ethiopia 12 13 14 Strengths and limitations of this study 15 16 For peer review only 17  This study is the first prospective follow-up study in Ethiopia to determine the experience 18 19 of women with breast and cervical cancer from the first symptom recognition through the 20 21 course of survivorship care using rigorous mixed methods. Being prospective follow-up 22 23 study design, allows us to test the temporal relationship between the explanatory variables 24 25 26 and outcome of the study. 27 28  Our study will try to capture approximately 90% of the incident cases of the city so that 29 30 generalization about women with breast and cervical cancer in the city will be possible 31

32 http://bmjopen.bmj.com/ 33 latter. 34 35  The study will identify gaps and barriers to receipt of cancer care in Addis Ababa from a 36 37 patient perspective, which will inform public health policies and clinical guidelines for 38 39

40 early detection and improving the quality of cancer care in Addis Ababa and other parts of on September 25, 2021 by guest. Protected copyright. 41 42 the country. It will also provide patient narratives and quantitative evidence to support 43 44 efforts to increase public awareness and advocate for increased resources to reduce 45 46 47 suffering and death from cancer in Ethiopia. 48 49  The retrospective nature of collecting information about dates of symptom recognition, and 50 51 medical consultations is prone to recall bias. Also, the interviews will be conducted in a 52 53 54 hospital setting and there is likely to be social desirability bias with under-reporting of time 55 56 delays and over-reporting of desirable behavior such as self-breast examination. 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3  Lost to follow-up could be another limitation of the study 4 5 6 7 INTRODUCTION 8 9 10 Breast and cervical cancers are the most commonly diagnosed cancers and the leading causes of 11 12 cancer death among women in Ethiopia and in other parts of sub-Saharan Africa,[1-3] accounting 13 14 for about half of all cancer cases and deaths.[4] These cancers have significant public health and 15 16 For peer review only 17 societal implications not only because they represent more than half of all cancer cases in women 18 19 but also because they most frequently occur in young or middle age [5, 6] when patients are in the 20 21 workforce, raising children, and supporting other family members. 22 23 24 The morbidity and mortality associated with breast and cervical cancer can be mitigated through 25 26 27 early detection and receipt of evidence-based, high quality care.[7] However, based on limited data, 28 29 a substantial proportion of women with breast and cervical cancer in Ethiopia present with 30 31 advanced-stage disease. For instance, about 71% of the breast cancer cases [6] and 84% cervical

32 http://bmjopen.bmj.com/ 33 cancer cases [5] in Ethiopia were diagnosed at advanced stage largely because of prolonged patient 34 35 36 intervals in seeking medical care after recognition of symptoms and provider/health systems 37 38 intervals in referral of patients to cancer treatment centers.[8, 9] Further, most women with breast 39 40 and cervical cancer in the country do not receive treatments consistent with the global standard of on September 25, 2021 by guest. Protected copyright. 41 42 43 care.[3] 44 45 46 In addition to early detection and receipt of standard treatments, survivorship care is an important 47 48 component of high quality of care across the cancer continuum. This could be assessed through 49 50 Patient Reported Outcomes (PROs) as well as physician ratings of patients’ wellbeing,[10] though 51 52 53 PROs are found to be better predictors of patients survival and are thought to be more useful for 54 55 making clinical decision about patient management.[10, 11] There is, however, limited 56 57 58 4 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 information on barriers to early detection and receipt of and completion of treatment and patient 4 5 6 reported outcomes among women with breast and cervical cancer in Ethiopia to guide public health 7 8 policies and patient management.[12] 9 10 11 Previous studies from Ethiopia have reported limited knowledge about breast and cervical cancer, 12 13 including about prevention, early detection, and treatment, among healthcare professionals [13- 14 15 16 16] and the generalFor population.[17-27] peer Thisreview limited awareness only likely contributes to the high 17 18 proportion of disease detected at advanced stage in the country.[5, 6] Notably, there are also studies 19 20 conducted on women with breast and cervical cancer.[5, 6, 8, 9, 28-33] Two of the studies [8, 28] 21 22 23 examined patient or diagnostic interval among women with breast cancer in Ethiopia and found 24 25 long waiting times to initiate medical consultation (average about 18 months). Similarly, Tadesse 26 27 reported that about 30% (56/198 patient) of women with cervical cancer visited 3 or more health 28 29 30 facilities before being referred to Tikur Anbessa Specialized Hospital (TASH), a referral public 31

32 hospital, for cancer-directed treatment and 20% (46) of the patients waited for more than 6 months http://bmjopen.bmj.com/ 33 34 from first health care visit before they were first seen at TASH.[34] 35 36 37 The aforementioned studies, however, were limited because of small sample sizes,[8, 28] and 38 39

40 reliance on data from chart review [6, 28-30] and data were collected from only one hospital, on September 25, 2021 by guest. Protected copyright. 41 42 TASH, which houses the only radiotherapy center in the country.[5, 6, 8, 28-30, 32] These all 43 44 could make them prone to incompleteness and limit their generalizability to elsewhere in Ethiopia. 45 46 47 Moreover, none of the studies examined the factors contributing to patient and diagnostic intervals, 48 49 patient reported outcomes, the relationship between patient/diagnostic intervals and stage at 50 51 diagnosis as well as its effect on the survival of women with breast and cervical cancer in Ethiopia. 52 53 54 To help address this information gap, we have established a cohort of newly diagnosed breast and 55 56 cervical cancer patients in Addis Ababa, capital city of Ethiopia. This paper describes the protocol 57 58 5 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 of the study, the first prospective follow-up study on cancer patients’ experience in the country 4 5 6 and perhaps in Africa. 7 8 9 METHODS 10 11 12 13 Aim of the study 14 15 1. To explore barriers to early diagnosis of women with breast and cervical cancer 16 For peer review only 17 2. To estimate the duration of patient, diagnostic and treatment initiation intervals of women 18 19 20 with breast and cervical cancer 21 22 3. To assess factors associated with patient, diagnostic and treatment initiation time intervals of 23 24 women with breast and cervical cancer 25 26 27 4. To examine the association between patient/diagnostic interval and stage at diagnosis 28 29 5. To determine patient reported outcomes (levels of fatigue, pain, sleep disorder, and 30 31 depression) 32 http://bmjopen.bmj.com/ 33 34 6. To describe treatment patterns and adherence by socio-demographic factors 35 36 7. To document survivorship care (e.g., surveillance for recurrence and late effects of treatment) 37 38 8. To estimate the financial burden of breast and cervical cancer on patients and their families 39 40 9. To estimate two-year survival rates and their associations with patient, diagnostic and on September 25, 2021 by guest. Protected copyright. 41 42 43 treatment initiation intervals, receipt of treatment, socio-demographic factors, financial 44 45 burden, and other patient reported outcomes. 46 47 48 Study setting 49 50 51 52 This study will be conducted in the Addis Ababa, which has a population of about 3.5 million.[35] 53 54 The city is served by 6 public and 36 private hospitals, 53 public health centers, and around 700 55 56 57 58 6 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 private clinics.[36] According to a national survey, the main health care providers for outpatients 4 5 6 was government health facilities (77%), followed by private health facilities (20%), traditional and 7 8 religious healers (2%), and Non-governmental organization (1%).[37] A population-based cancer 9 10 registry has been in place since 2011 in Addis Ababa, with incident cases collected from 20 health 11 12 facilities including referral hospitals, higher clinics, and diagnostic centers.[4] Our study will 13 14 15 recruit all women with breast and cervical cancer aged >18 years diagnosed from January 1, 2017 16 For peer review only 17 – June 30, 2018 in 7 major health facilities. Of which, two are public (TASH, and St. Paul Hospital 18 19 Millennium Medical College) and five are private (United Vision Medical Services Center, 20 21 22 Hallelujah General Hospital, Betezata Hospital, Legehar Hospital and Landmark Hospital). These 23 24 health facilities capture more than 90% of all women with breast and cervical cancer reported to 25 26 the cancer registry in Addis Ababa. Recruitment of the study participants has been started on 27 28 29 March 20, 2017. 30 31

32 Study designs and sample size http://bmjopen.bmj.com/ 33 34 35 The study design is a prospective follow-up study, using mixed methods (both quantitative and 36 37 qualitative). The quantitative component involves both cross sectional and prospective follow-up 38 39

40 study designs, while the qualitative study is phenomenological study. The latter study design will on September 25, 2021 by guest. Protected copyright. 41 42 help to understand the breast and cervical cancer patients’ experience of their life before and after 43 44 diagnosis, and during the course of treatment.[11] We expect to recruit about 450 breast and 250 45 46 47 cervical cancer patients, based on the number of breast and cervical cases recorded each year in 48 49 the city over the past two years,[38] and they will be followed for two years. 50 51 52 The adequacy of the above estimated cohort of 450 breast and 250 cervical cancer patients to 53 54 55 address the stated specific objectives of the study was assessed. For instance, to estimate the 56 57 58 7 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 sample size for the second specific objective (duration of patient and diagnostic waiting times), 4 5 6 we used single population proportion formula. Taking expected proportion (p=31.7%) of patient 7 8 interval (>3 months) from a similar study,[39] 95% confidence level (Zα/2=1.96) and a 5% 9 10 precision, a minimum of 333 patients are required for the study. In contrast, the minimum sample 11 12 sizes for the third (factors associated with patient and provider time intervals), fourth (the 13 14 15 association between patient or provider interval and stage at diagnosis) and ninth specific objective 16 For peer review only 17 (survival rate of the patients) were estimated using two population proportion formula assuming 18 19 95% confidence level and 80% power, the estimates were found to be 422, 354 and 178 patients, 20 21 22 respectively. To increase the precision of the estimates of the different outcomes of the study, all 23 24 of the cohort of 450 breast and 250 cervical cancer cases will be considered in the analysis of each 25 26 of the specific objectives. 27 28 29 30 Data collection tools and techniques 31

32 http://bmjopen.bmj.com/ 33 Three data collection tools will be used to address the objectives of the project: an interviewer 34 35 administered questionnaire (Supplemental File), an in-depth interview guide, and a medical record 36 37 data extraction tool. The tools are being developed in English, translated into Amharic, and back 38 39 translated into English. The Amharic version will be used for conducting the interview. 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 The interviewer administered questionnaire is organized into two parts. The first part of the 44 45 questionnaire addresses participants’ socio-demographic characteristics, medical history, and 46 47 pathway to diagnosis which is adapted from a questionnaire for a similar study in Rwanda.[40] In 48 49 50 addition, this first phase of questionnaire also includes questions about patient reported outcomes 51 52 (levels of fatigue, pain, sleep disorder and depression). Depression was assessed using a validated 53 54 Patient Health Questionnaire-9 (PHQ-9).[41]. While the questions for fatigue, pain and sleeping 55 56 57 58 8 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 disorder were adopted from National Cancer Institute.[42, 43] This questionnaire will be 4 5 6 administered face to face by trained interviewers at the time of participants’ recruitment. 7 8 9 The second tool which will be administered at about one year after the diagnosis of the cases 10 11 investigates receipt of and adherence to treatments, financial hardship, and survivorship care 12 13 (Supplemental File). The questions are adapted from different standardized tools developed by the 14 15 16 National Cancer Institute,[42,For peer 43] the Agency review for Healthcare only Research and Quality, the Centers 17 18 for Disease Control and Prevention of the U.S. Department of Health and Human Services.[44] To 19 20 improve the validity of the questions, the adapted questionnaire was reviewed by local and 21 22 23 international experts on the research subject and cancer care. Further, a pretest was performed to 24 25 enhance the clarity of the tool. Patients will be interviewed about one year after their cancer 26 27 diagnosis by a trained interviewer, in person when possible and by telephone otherwise. Phone 28 29 30 calls will be made at least three times at different times of the day, evening and weekends to 31

32 increase the response rate of the study participants. Those patients who are not interviewed through http://bmjopen.bmj.com/ 33 34 this mechanism, will be considered as lost to follow-up.[45] For patients who died or are too ill to 35 36 be interviewed, a surrogate (relative or household member) familiar with their cancer care will be 37 38 39 interviewed.

40 on September 25, 2021 by guest. Protected copyright. 41 42 The medical record data extraction tool will be used to collect information about date of diagnosis, 43 44 tumor characteristics (e.g., stage at diagnosis, metastasis and recurrence), initiation and completion 45 46 47 of treatments, and vital status from the medical charts of the patients. Medical record review will 48 49 occur at about one and two years after diagnosis. 50 51 52 In addition to the interviewer-administered questionnaire and extraction tool, a semi-structured 53 54 55 interview guide will be developed and used for in-depth interviews. This instrument will include 56 57 58 9 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 patients’ knowledge and perception of breast and cervical cancer, and the patients’ experience 4 5 6 from the recognition of first symptom of the disease to diagnosis and treatment. Interviews will be 7 8 conducted in local language (Amharic). The principal investigator and two trained data collectors 9 10 who have experience in collecting qualitative data will conduct the in-depth interviews. Interview 11 12 guide and tape recorder will be used. The interviewers will use probing and question-rephrasing 13 14 15 techniques to clarify questions and obtain details from the respondents. The number of interviews 16 For peer review only 17 will be determined based on information saturation. 18 19 20 21 Term definitions and measurements 22 23 Independent variables: Demographic variables (age at diagnosis, marital status, and age at first 24 25 26 child birth), socioeconomic variables (level of education, occupation, monthly family income, and 27 28 source of medical expenses), method of initial detection, time of first symptom/sign detection, 29 30 participant’s appraisal of first symptom/sign, participants immediate action to the first symptom, 31

32 http://bmjopen.bmj.com/ 33 triggers to seek medical care, health facility of the first medical consultation, number of healthcare 34 35 facilities visited before diagnosis, number of visits to healthcare facility before diagnosis, clinical 36 37 presentation at time of diagnosis, time of medical care sought, family history of breast/cervical 38 39 cancer, self-reported co-morbidities and traditional medicine use will be obtained through in 40 on September 25, 2021 by guest. Protected copyright. 41 42 person face to face interview. 43 44 45 The existing literature lacks consistency in the definition of the time intervals for cancer diagnosis 46 47 and treatment delays, and traditionally has been classified as “patient delay” and “system 48 49 delay”.[46] For consistency, the Aarhus statement [47] recommended classifying these as “patient 50 51 52 interval”, “diagnostic interval”, “treatment interval” and “total interval”. Our study is based on this 53 54 framework. Patient interval is defined as the interval from the date of first recognition of symptoms 55 56 57 58 10 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 (the time point when first bodily changes and/or symptoms are noticed) to the date of first clinical 4 5 6 presentation (the date at which the patient first presented to a healthcare provider after first 7 8 recognition of symptoms).[47] Waiting for > 3 months before consulting a health care provider 9 10 will be considered to be a long patient interval.[48-50] 11 12 13 We will consider using local events to help patients recall the date of first symptom recognition 14 15 16 and presentation. If Forthe participants peer are unable review to recall the exact only date of first symptom recognized 17 18 or date of first medical consultation made, they will be asked to provide a month, or year (was it 19 20 at the beginning, middle, or end of the year). If they remembered the month, the date will be 21 22 th 23 estimated as the 15 of that month; if the participants only said the beginning, middle or end of 24 25 the year, the estimated date will be 15th of February, June or October of the year, respectively. 26 27 While for those who are only able to provide the year, the estimated date will be June 30th of that 28 29 30 year.[40] 31

32 http://bmjopen.bmj.com/ 33 Diagnostic interval is defined as the interval from the date of first clinical presentation to the date 34 35 of pathologic diagnosis (the date at which the first histological or cytological confirmation of this 36 37 malignancy was reported). Treatment interval will be computed by subtracting the date of 38 39

40 confirmation from the date of treatment initiation. Total interval will be computed by subtracting on September 25, 2021 by guest. Protected copyright. 41 42 the date of first time recognition of symptom from the date of treatment initiation.[47] The date of 43 44 diagnosis and treatment initiation will be taken from the medical chart of the patients. 45 46 47 48 Stage at diagnosis will be grouped into early stage (patient presented with clinical stage II and 49 50 below) and advanced stage (patients presented with clinical stage III or above) diseases.[51, 52] 51 52 53 54 55 56 57 58 11 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 12 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Data quality assurance mechanism 4 5 6 Several measures will be taken to maintain the quality of the research starting from designing the 7 8 9 tool to data analysis and interpretations of the findings. Tool translation and back translation will 10 11 be done to ensure the consistency of the survey tools. In addition to this, the questionnaire will be 12 13 pre-tested and relevant corrections will be made. 14 15 16 Data collectors andFor supervisor peer will be recruitedreview based on only the level of education, ability to 17 18 19 communicate using the working language, and experience on data collection. Moreover, they will 20 21 be trained on the objectives of the study, data collection tools, interviewing techniques, and ethical 22 23 procedures before the implementation of the project. 24 25 26 In addition to the training of the data collectors, they will be supervised by the supervisor and 27 28 29 principal investigators. Filled questionnaires will be checked for their completeness and 30 31 consistency on daily bases by the supervisor. Biweekly meetings will be held with the supervisor

32 http://bmjopen.bmj.com/ 33 of the data collectors and the investigators to discuss and solve any problems encountered in the 34 35 data collection process. 36 37 38 39 To minimize errors during data entry, templates will be developed using Epi-Info using check

40 on September 25, 2021 by guest. Protected copyright. 41 codes. After the entry is completed, the sample of the questionnaires will be rechecked for 42 43 correctness against the raw data, and necessary corrections will be made before the analysis. 44 45 46 47 To maintain the trustworthiness of the qualitative data, interviews will be collected, transcribed 48 49 and analyzed by individuals experienced in qualitative data collection and analysis. All interviews 50 51 will be tape recorded to grasp all the points during the interview. Moreover, data will be transcribed 52 53 by the data collectors on a daily bases to maintain the consistency and context of the discussion, 54 55 56 and checked for errors by listening back to the audio-recording and reading the transcripts 57 58 12 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 13 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 simultaneously. Finally, the transcribed data will be coded using NVivo software to facilitate the 4 5 6 reduction of the qualitative data without missing the central idea. 7 8 9 Data management and analysis plan 10 11 12 Qualitative data analysis 13 14 15 Specific objective 1: For the qualitative data, audio data will be transcribed verbatim into 16 For peer review only 17 Microsoft Word files and translated from the local language to English. Before the analysis, the 18 19 text will be read through several times to obtain a sense of the whole and familiarize with the 20 21 22 data. Then word transcript of the data will be imported into NVivo software version 11 [53] and 23 24 coded line by line. The codes will be compared based on differences and similarities and sorted 25 26 into categories, and categories will be grouped in themes. Finally, the result will be presented in 27 28 29 themes. 30 31

32 Quantitative data entry, cleaning and management http://bmjopen.bmj.com/ 33 34 35 Deidentified data will be entered to the pre-designed template with appropriately programed 36 37 skipping patterns using Epi-Info 3.5.1 version. Cleaned data will be exported to Stata 14 software 38 39 to calculate summary descriptive statistics, including mean (standard deviation) and median 40 on September 25, 2021 by guest. Protected copyright. 41 42 (interquartile range) for continuous variable and proportions for categorical variables. Estimates 43 44 of population parameters will be presented with their 95% Confidence Interval. P-value of less 45 46 than 0.05 will be taken as significance level. Follows analytical methods for each of the specific 47 48 49 objectives: 50 51 52 Specific objective 2 (to determine the duration of patient, diagnostic and treatment initiation 53 54 intervals) a descriptive analysis will be used. We will present means with their standard deviation 55 56 57 58 13 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 (SD) for those with normal distribution, and median and interquartile range (IQR) for those 4 5 6 variables with skewed distributions. In addition, we will calculate proportions with their 95%CI 7 8 for patients who waited > 3 months before seeking medical care and for those patients who 9 10 waited more than two weeks before receipt of diagnosis confirmation following date of 11 12 presentation. 13 14 15 16 Specific objective 3For and 4: Topeer determine reviewfactors associated onlywith patient and diagnostic waiting 17 18 times, and the degree of association between patient/diagnostic intervals and stage at diagnosis, 19 20 we first run bivariate analyses to select candidate explanatory variables. Variables reported as 21 22 23 having an impact on longer interval, and survival in the literature, and those variables which show 24 25 significant association (P<0.25) with the dependent variable in the bivariate analysis will be 26 27 entered into the multivariable logistic regression model to identify their independent effects. 28 29 Before fitting the binary logistic regression model multi-collinearity among the independent 30 31

32 variables, outliers, and model fitness will be checked. Odds Ratio with its 95% confidence interval http://bmjopen.bmj.com/ 33 34 will be calculated for each independent variable against the dependent variable. Then, statistical 35 36 significance will be declared at P value < 0.05. 37 38 39 Specific objective 5 (to determine patient reported outcomes). Prevalence of cancer caused pain, 40 on September 25, 2021 by guest. Protected copyright. 41 42 fatigue, and sleeping disorder will be computed. Depression will be measured by 9 items. Each 43 44 item is rated on a 3-point scale, giving maximum scores of 27. The total depression score will be 45 46 determined, and variation of depression scores at two time points (during diagnosis or treatment 47 48 49 and after treatment) will be assessed using repeated measures analysis. Then we will test for the 50 51 presence of statistical difference of the score across different participants’ characteristics, and 52 53 receipt of treatment. 54 55 56 57 58 14 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Specific objective 6 and 7 (to describe treatment patterns, adherence and survivorship care): 4 5 6 descriptive statistics will be used to characterize the treatment pattern received by the patients 7 8 and level of adherence. We will compute the proportion (with 95% CI) of patients who received 9 10 radiotherapy, chemotherapy, hormonal therapy and survivorship care. In addition, multivariable 11 12 logistic regression analysis will be conducted to examine the association between participants 13 14 15 characteristics and three separate outcomes: (1) receipt of radiotherapy and chemotherapy; (2) 16 For peer review only 17 adherence to chemotherapy and hormonal therapy; and (3) receipt of survivorship care. Variables 18 19 with P values < 0.25 on bivariate analysis will be retained in the final multivariable logistic 20 21 22 regression. 23 24 25 Specific objective 8 (to estimate the financial burden of breast and cervical cancer on patients 26 27 and their families): data will be analyzed descriptively and both the direct and indirect patient 28 29 related costs will be computed. The mean or median cost of illness will be computed. Financial 30 31

32 difficulties and coping mechanisms made by the patients will be described. http://bmjopen.bmj.com/ 33 34 35 Specific objective 9 (to compute the two-year survival rates and the determinants of survival): 36 37 Survival will be estimated using the Kaplan-Meier method and compared using the log-rank test. 38 39 The time to event for the following three types of survival rates will be computed as follow [54]: 40 on September 25, 2021 by guest. Protected copyright. 41 42 43  Disease Free Survival (DFS) will be computed for stage I-III cases treated with curative 44 45 intention from the date of primary treatment to the date of local, contra-lateral or distant 46 47 recurrence or death from breast or cervical cancer. 48 49 50  Distant DFS will be computed from the date of primary treatment to the date of distant 51 52 metastasis or death from breast or cervical cancer. 53 54  Overall Survival (OS) will be computed from the date of diagnosis to the date of death. 55 56 57 58 15 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3  For patients who remained alive and disease-free, data will be censored at the date of the 4 5 6 last contact. 7 8 We will also compute hazard ratio (HR) for time to event outcomes, with its corresponding 95% 9 10 CIs, and associated p-values. Cox’s proportional hazard model will be used to identify factors 11 12 13 associated with the survival of the patients. Overall survival will be estimated using the Kaplan- 14 15 Meier method and compared using the log-rank test. The proportional hazards assumption will be 16 For peer review only 17 checked using graphical method and goodness of fit test. Multivariable Cox regression analysis 18 19 will be used to estimate the hazard of all-cause mortality (HR) associated with the pre-selected 20 21 22 various prognostic factors that we are studying. 23 24 25 Patient and public involvement 26 27 28 Neither patients nor the public were involved in the design of the study, the types of research 29 30 questions and study outcomes, or recruitment of participants. However, we conducted a rapid 31

32 http://bmjopen.bmj.com/ 33 ethical assessment among women with breast and cervical cancer, family members, and health 34 35 care providers for designing consent of study participants. We plan to disseminate the results of 36 37 this research to study participants, staff of healthcare facilities where the study participants are 38 39 recruited, Addis Ababa Health Bureau, Federal Ministry of Health, cancer control advocates, 40 on September 25, 2021 by guest. Protected copyright. 41 42 media, and researchers through preparation of fact sheets for lay audience, publications in 43 44 international peer-reviewed journals, and presentations in conferences. 45 46 47 48 Ethical considerations and result dissemination 49 50 Ethical clearance has been secured from the Institutional Review Board (018/17/SPH) of Addis 51 52 53 Ababa University, College of Health Science. Prior to the start of study subjects’ recruitment, we 54 55 conducted rapid ethical assessment to design our consent process.[55] Based on this assessment, 56 57 58 16 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 we found that most of the participants were not comfortable to written consent for different reasons. 4 5 6 Accordingly, we decided to use verbal consent, which has been approved by the IRB of College 7 8 of Health Science of Addis Ababa University. Eligible patients will be verbally informed, by 9 10 trained research personnel, regarding the nature and purpose of the study, and given time to decide 11 12 whether or not to participate in the follow-up study. Enrollment will be fully based on the voluntary 13 14 15 participation of the study participants and respondents who are interested to avoid specific 16 For peer review only 17 questions or discontinue the interview will be allowed to do so. In the event family members are 18 19 grieving when contacted for vital status, we will offer our condolences and ask then them if they 20 21 22 will be willing to speak with us at a later time. 23 24 Confidentiality of any information related to the patient and her clinical history will be maintained 25 26 by keeping both the hard copy and softcopy of every collected data in a locked cabinet and 27 28 29 password secured computer. Only the principal investigators will have access to the deidentified 30 31 data that will be kept in a secure place. All data will be coded without personal identifiers. All

32 http://bmjopen.bmj.com/ 33 analyses will be on deidentified and coded data. 34 35 We intend to present the results of our follow-up study via scientific publications in peer-reviewed 36 37 38 journals as well as through presentation to stakeholders including the public, patients, clinicians 39

40 and policymakers. on September 25, 2021 by guest. Protected copyright. 41 42 43 Information gathered from this study will inform clinical guidelines and public health policies 44 45 46 improve the quality of cancer patients’ care delivered in the city, as well as other parts of the 47 48 country. It will also be used to produce fact-based materials to develop "stories" that illustrate the 49 50 compelling need for increased resources to reduce suffering and death from cancer. Experience of 51 52 53 the survivors will become available and presented to the public to enrich awareness campaigns 54 55 and show that cancer is not a death sentence [56] but patients can as well be cured. Furthermore, 56 57 58 17 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 this collaborative project will provide research collaboration opportunities for several graduate 4 5 6 students, residents, and junior and senior faculty members of Addis Ababa University and in doing 7 8 so will enhance the capacity of the university in conducting cancer care delivery and epidemiologic 9 10 research. 11 12 13 14 Supplemental Files 15 16 For peer review only 17 Supplemental file 1: Questionnaire 18 19 20 21 Acknowledgements 22 23 24 25 The authors would like to thank the study participants, data collectors, and supervisors. 26 27 Authors’ contributions 28 29 30 AG, AA, AWY, MA, and AJ conceptualize the study. AG wrote the first draft of the manuscript. 31

32 http://bmjopen.bmj.com/ 33 AA, AWY, SH, MA, EJK, LEP, and AJ commented on the designing the study and reviewed the 34 35 final draft of the manuscript. All authors read and approved the final draft of the manuscript. 36 37 Funding 38 39

40 This project is supported by the Intramural Research Department of the American Cancer on September 25, 2021 by guest. Protected copyright. 41 42 Society. The funder has no role in the study design; in the collection, analysis and interpretation 43 44 45 of the data; in the writing of the report; and in the decision to submit the paper for publication. 46 47 Competing interests 48 49 The authors declare that they have no competing interests. 50 51 52 53 REFERENCES 54 1. Torre LA, Islami F, Siegel RL, et al. Global Cancer in Women: Burden and Trends. Cancer 55 56 Epidemiol Biomarkers Prev;2017;26(4):444-457 57 58 18 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 2. Kantelhardt EJ, Gizaw M, Getachew S, et al. A Review on Breast Cancer Care in Africa. Breast 4 5 Care. 2015;10:364-70. 6 3. Jemal A, Bray F, Forman D, et al. Cancer Burden in Africa and opportunities for prevention. Cancer. 7 8 2012;118:4372-84. 9 10 4. Timotewos G, Solomon A, Mathewos A, et al. First data from a population based cancer registry in 11 Ethiopia. Cancer epidemiology. 2018;53:93-8. PubMed PMID: 29414637. Epub 2018/02/08. eng. 12 13 5. Kantelhardt EJ, Moelle U, Begoihn M, et al. Cervical cancer in Ethiopia: Survival of 1,059 patients 14 who received oncologic therapy. The Oncologist. 2014;19:727-34. 15 16 6. Kantelhardt E.J, ZercheFor P, Mathewospeer A, etreview al. Breast cancer survival only in Ethiopia: A cohort study of 17 1,070 women. Int J Cancer. 2013;135:702–9. 18 19 7. World Health Organization. Global status report on noncommunicable diseases 2010. Geneva, 20 21 Switzerland: 2011.accessed on october 15, 2018 from 22 https://www.who.int/nmh/publications/ncd_report2010/en/ 23 24 8. Dye TD, Bogale S, Hobden C, et al. Experience of initial symptoms of breast cancer and triggers for 25 action in Ethiopia. Hindawi Publishing Corporation, International Journal of Breast Cancer. 26 27 2012;2012:1-5. 28 9. Dye TDV, Bogale S, Hobden C, et al. A mixed-method assessment of beliefs and practice around 29 30 breast cancer in Ethiopia: Implications for public health programming and cancer control. Global 31

32 Public Health, An International Journal for Research, Policy and Practice. 2011;6:719-31. http://bmjopen.bmj.com/ 33 10. Montazeri A. Quality of life data as prognostic indicators of survival in cancer patients: an overview 34 35 of the literature from 1982 to 2008. Health and Quality of Life Outcomes. 2009;7:1-21 36 11. Montazeri A. Health-related quality of life in breast cancer patients: A bibliographic review of the 37 38 literature from 1974 to 2007. Journal of Experimental & Clinical Cancer Research. 2008;27:1-31 39 12. The Federal Democratic Republic of Ethiopia Ministry of Health. Health Sector Transformation Plan 40 on September 25, 2021 by guest. Protected copyright. 41 2015/16 - 2019/20. 2015. Accessed on Dec. 2018, from file:///C:/Users/user/Downloads/ethiopia- 42 43 health-system-transformation-plan.pdf 44 13. Lemlem SB, Sinishaw W, Hailu M, et al. Assessment of knowledge of breast cancer and screening 45 46 methods among nurses in university hospitals in Addis Ababa, Ethiopia, 2011. Hindawi Publishing 47 Corporation. 2013;2013:1-8. 48 49 14. Azage M, Abeje G, Mekonnen A. Assessment of factors associated with breast self-examination 50 51 among health extension workers in West Gojjam Zone, Northwest Ethiopia. Hindawi Publishing 52 Corporation International Journal of Breast Cancer. 2013;2013:1-6. 53 54 15. Dulla D, Daka D, Wakgari N. Knowledge about cervical cancer screening and its practice among 55 female health care workers in southern Ethiopia: a cross-sectional study. International journal of 56 57 58 19 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 20 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 women's health. 2017;9:365-72. PubMed PMID: 28579837. Pubmed Central PMCID: PMC5446960. 4 5 Epub 2017/06/06. eng. 6 16. Wondimu YT. Cervical cancer: assessment of diagnosis and treatment facilities in public health 7 8 institutions in Addis Ababa, Ethiopia. Ethiopian medical journal. 2015;53:65-74. PubMed PMID: 9 10 26591294. Epub 2015/11/26. eng. 11 17. Hailu T, Berhe H, Hailu D, et al. Knowledge of breast cancer and its early detection measures among 12 13 female students, in Mekelle University, Tigray region, Ethiopia. Science Journal of Clinical 14 Medicine. 2014;3:57-64. 15 16 18. Legesse B, Gedif ForT. Knowledge peer on breast reviewcancer and its prevention only among women household heads 17 in Northern Ethiopia. Open Journal of Preventive Medicine. 2014;4:32-40. 18 19 19. Birhane N, Mamo A, Girma E, et al. Predictors of breast self - examination among female teachers in 20 21 Ethiopia using health belief model. Archives of Public Health. 2015;73:4-7. 22 20. Shiferaw N, Brooks MI, Salvador-Davila G, et al. Knowledge and awareness of cervical cancer 23 24 among HIV-infected women in Ethiopia. Obstetrics and gynecology international. 2016;2016:1-19. 25 PubMed PMID: 27867397. Pubmed Central PMCID: PMC5102747. Epub 2016/11/22. eng. 26 27 21. Aweke YH, Ayanto SY, Ersado TL. Knowledge, attitude and practice for cervical cancer prevention 28 and control among women of childbearing age in Hossana Town, Hadiya zone, Southern Ethiopia: 29 30 Community-based cross-sectional study. PloS one. 2017;12:1-18. PubMed PMID: 28742851. 31

32 Pubmed Central PMCID: PMC5526548. Epub 2017/07/26. eng. http://bmjopen.bmj.com/ 33 22. Tefera F, Mitiku I. Uptake of cervical cancer screening and associated factors among 15-49-year-old 34 35 women in Dessie Town, Northeast Ethiopia. Journal of cancer education : the official journal of the 36 American Association for Cancer Education. 2016;32:901-907. PubMed PMID: 27075197. Epub 37 38 2016/04/15. eng. 39 23. Mitiku I, Tefera F. Knowledge about cervical cancer and associated factors among 15-49 year old 40 on September 25, 2021 by guest. Protected copyright. 41 women in Dessie Town, Northeast Ethiopia. PloS one. 2016;11(9):e0163136. PubMed PMID: 42 43 27690311. Pubmed Central PMCID: PMC5045174. Epub 2016/10/01. eng. 44 24. Getahun F, Mazengia F, Abuhay M, et al. Comprehensive knowledge about cervical cancer is low 45 46 among women in Northwest Ethiopia. BMC cancer. 2013;13:2. PubMed PMID: 23282173. Pubmed 47 Central PMCID: PMC3559275. Epub 2013/01/04. eng. 48 49 25. Bayu H, Berhe Y, Mulat A, et al. Cervical cancer screening service uptake and associated factors 50 51 among age eligible women in Mekelle Zone, Northern Ethiopia, 2015: A community based study 52 using health belief model. PloS one. 2016;11(3):e0149908. PubMed PMID: 26963098. Pubmed 53 54 Central PMCID: PMC4786115. Epub 2016/03/11. eng. 55 56 57 58 20 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 21 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 26. Birhanu Z, Abdissa A, Belachew T, et al. Health seeking behavior for cervical cancer in Ethiopia: a 4 5 qualitative study. International journal for equity in health. 2012;11:83. PubMed PMID: 23273140. 6 Pubmed Central PMCID: PMC3544623. Epub 2013/01/01. eng. 7 8 27. Belete N, Tsige Y, Mellie H. Willingness and acceptability of cervical cancer screening among 9 10 women living with HIV/AIDS in Addis Ababa, Ethiopia: a cross sectional study. Gynecologic 11 oncology research and practice. 2015;2:6. PubMed PMID: 27231566. Pubmed Central PMCID: 12 13 PMC4881166. Epub 2015/01/01. eng. 14 28. Ersumo T. Breast Cancer in an Ethiopian population, Addis Ababa. East and Central African Journal 15 16 of Surgery.2006;11:81-85.For peer review only 17 29. Abate SM, Yilma Z, Assefa M, et al. Trends of Breast Cancer in Ethiopia. Int J Cancer Res Mol 18 19 Mech. 2016;2:1-5. 20 21 30. Kantelhardt EJ, Assefa M, Abreha A, et al. The prevalence of estrogen receptor-negative breast 22 cancer in Ethiopia. BMC cancer. 2014;14:1-6. 23 24 31. Hailu A, Mariam DH. Patient side cost and its predictors for cervical cancer in Ethiopia: a cross 25 sectional hospital based study. BMC Cancer. 2013;13:1-8. 26 27 32. Dye TD, Bogale S, Hobden C, et al. Complex care systems in developing countries: Breast Cancer 28 Patient Navigation in Ethiopia. American Cancer Society. 2010;116:577-85. 29 30 33. Gizaw M, Addissie A, Getachew S, et al. Cervical cancer patients presentation and survival in the 31

32 only oncology referral hospital, Ethiopia: a retrospective cohort study. Infect Agent Cancer. http://bmjopen.bmj.com/ 33 2017;12:61. PubMed PMID: 29213299. Pubmed Central PMCID: 5708091. Epub 2017/12/08. eng. 34 35 34. Tadesse SK. Socio-economic and cultural vulnerabilities to cervical cancer and challenges faced by 36 patients attending care at Tikur Anbessa Hospital: a cross sectional and qualitative study. BMC 37 38 Women's Health. 2015;15:1-12 39 35. Federal Democratic Repeblic of Ethiopia Centeral statistics Agency. Population Projection of 40 on September 25, 2021 by guest. Protected copyright. 41 Ethiopia for all regions at wereda level from 2014 – 2017 assessed on Nov. 23, 2016 from 42 43 www.csa.gov.et/. 2013. 44 36. City Government of Addis Ababa Bureau of Finance and Economic Development. Socio-Economic 45 46 Profile of Addis Ababa For the Year 2004 E.C/2011/12G.C. Accessed on Nov. 26, 2016 from 47 www.aabofed.gov.et/Documents/Addis%20Ababa%20Profile%20%202004%20E.pdf. 2013. 48 49 37. Ethiopia Federal Ministry of Health. Ethiopia’s Household Health Services Utilization and 50 51 Expenditure Survey Briefing Notes. Addis Ababa, Ethiopia. 2014:5 accessed from 52 https://www.hfgproject.org/wp-content/uploads/2014/04/Ethiopia-NHA-Survey-Briefing-Notes.pdf 53 54 55 56 57 58 21 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 22 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 38. African Cancer Regisrty Network. Addis Ababa population Based cancer registery. Addis Ababa City 4 5 Cancer Registry - African Cancer Registry Network afcrn.org/membership/members/100-Addisababa 6 [cited 2016 June 27]. 7 8 39. Harirchi I, Karbakhsh M, Hadi F, et al. Patient delay, diagnosis delay and treatment delay for breast 9 10 cancer: Comparison of the pattern between patients in public and private health sectors. Arch Breast 11 Cancer. 2015; 2:15-20 12 13 40. Pace LE, Mpunga T, Hategekimana V, et al. Delays in Breast Cancer PresentationandDiagnosis at 14 TwoRural Cancer Referral Centers in Rwanda. The Oncologist. 2015;20:780-8. 15 16 41. Hanlon C, MedhinFor G, Selamu peer M, et al. Validity review of brief screening only questionnaires to detect depression 17 in primary care in Ethiopia. Journal of affective disorders. 2015 Nov 1;186:32-9. PubMed PMID: 18 19 26226431. Epub 2015/08/01. eng. 20 21 42. National Cancer Instutite and Northern California. Assessment of Patients’ Experience of Cancer 22 Care (APECC) Study. Accessed from https://healthcaredelivery.cancer.gov/apecc/ 23 24 43. National Cancer Instutite U.S. Department of Health and Human Services National Institutes of 25 26 Health. Adolecent and Young Adult Health Outcome and Patient Experiance. Follow-up survey. 27 44. The Agency for Healthcare Research and Quality and The Centers for Disease Control and 28 29 Prevention of the U.S. Department of Health and Human Services. Medical Expenditure Survey. 30 Your Experiences with Cancer. Accessed from https://healthcaredelivery.cancer.gov/meps/ 31

32 45. Harlan LC, Lynch CF, Keegan THM, et al. Recruitment and follow-up of adolescent and young adult http://bmjopen.bmj.com/ 33 cancer survivors: the AYA HOPE Study. J Cancer Surviv. 2011;5:305-14. 34 35 46. Freitas AG, Weller M. Patient delays and system delays in breast cancer treatment in developed and 36 37 developing countries. Cien Saude Colet. 2015;20:3177-89. PubMed PMID: 26465859. Epub 38 2015/10/16. eng. 39

40 47. Weller D, Vedsted P, Rubin G, et al. The Aarhus statement: improving design and reporting of on September 25, 2021 by guest. Protected copyright. 41 studies on early cancer diagnosis. Br J Cancer. 2012;106:1262-7. PubMed PMID: 22415239. Pubmed 42 43 Central PMCID: 3314787. Epub 2012/03/15. eng. 44 45 48. Sharma K, Costas A, Damuse R, et al. The Haiti Breast Cancer Initiative: Initial Findings and 46 Analysis of Barriers-to-Care Delaying Patient Presentation. Hindawi Publishing Corporation: Journal 47 48 of Oncology. 2013;2013:1-6 49 49. Ramirez AJ, Westcombe AM, Burgess CC, et al. Factors predicting delayed presentation of 50 51 symptomatic breast cancer: a systematic review. Lancet. 1999;353:1127-31. 52 50. Sharma K, Costas A, Shulman LN, et al. A Systematic review of barriers to breast cancer care in 53 54 developing countries resulting in delayed patient presentation. Hindawi Publishing Corporation 55 56 Journal of Oncology. 2012;2012:1-8 57 58 22 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 23 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 51. Edge SB. AJCC cancer staging manual. 7th ed. . New York: Springer; 2010. Accessed on January 4 5 2018 from https://cancerstaging.org/references- 6 tools/deskreferences/Documents/AJCC%207th%20Ed%20Cancer%20Staging%20Manual.pdf 7 8 52. Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol 9 10 Obstet. 2009;105:107-8. PubMed PMID: 19342051. Epub 2009/04/04. eng. 11 53. Hamunyela RH, Serafin AM, Akudugu JM. Strong synergism between small molecule inhibitors of 12 13 HER2, PI3K, mTOR and Bcl-2 in human breast cancer cells. Toxicology in vitro : an international 14 journal published in association with BIBRA. 2017;38:117-23. PubMed PMID: 27737796. Epub 15 16 2016/10/21. eng. For peer review only 17 54. Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end 18 19 points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25:2127-32. PubMed 20 21 PMID: 17513820. Epub 2007/05/22. eng. 22 55. Gebremariam A, Yalew AW, Hirpa S, et al. Application of the rapid ethical assessment approach to 23 24 enhance the ethical conduct of longitudinal population based female cancer research in an urban 25 setting in Ethiopia. BMC Medical Ethics. 2018;19:1-12. 26 27 56. Azubuike SO, Muirhead C, Hayes L, et al. Rising global burden of breast cancer: the case of sub- 28 Saharan Africa (with emphasis on Nigeria) and implications for regional development: a review. 29 30 World Journal of Surgical Oncology. 2018;16:1-13. 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 23 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 24 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4 Annexes 5 6 Annexe I Breast Cancer Survey English Version Questionnaire 7

8 Questionner ID. ______9

10 Patient’s Medical Record Number ______11

12 Name of the Health facility______13 14 PART I Informed Consent Form for Breast Cancer Participants 15 16 Information Sheet For peer review only 17 Introduction: Thank you so much. My name is ______. I am doing on behalf of 18 19 Addis Ababa University and American cancer society for the project entitled breast and cervical cancer 20 21 patients’ journey. 22 Question: Please can you tell me why you come to this health facility? 23 24 ______25 ______26 27 This is a research project on newly diagnosed breast cancer patients in Addis Ababa. Breast cancer is one 28 29 of the leading causes of morbidity and mortality among Ethiopian women. We are going to give you 30 information about the research project and invite you to be part of it. You may take some time to decide on 31

32 whether or not you will participate in the research. Before you decide, you can talk to anyone you feel http://bmjopen.bmj.com/ 33 comfortable with about the research 34 35 36 Purpose of the research: Although Breast cancer can be detected early and treated, most breast cancer 37 38 patients in Addis Ababa and Ethiopia present very late, after the disease spread to other parts of the body. 39 However, very little is known about the causes of their delay. Also unknown are their pathways to treatment 40 on September 25, 2021 by guest. Protected copyright. 41 and psychosocial wellbeing, and the financial burden of the disease on them and their families. In this study, 42 we are planning to assess the health seeking behavior, treatment pathways; patient reported outcomes, 43 44 financial burden and survival of newly diagnosed breast cancer patients in Addis Ababa. 45 46 47 Participation: We are asking you and others to voluntarily participate in this study because you have been 48 recently diagnosed with breast cancer. Over the next two years, we will have additional questionnaire to 49 50 learn about your experience related to your disease. Our study is completely interview based and does not 51 involves any invasive procedure. 52 53 54 Confidentiality: Any information that we collect about you during this research will be kept confidential. 55 Information about your identity will be put away after re-coding your file, and kept in a secured place. Only 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 25 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 the principal investigators will be able to link your identity with the code number, should this become 4 5 necessary to assist you medically. However, all the clinical information, which is devoid of your identity, 6 may be seen by the researchers; and if need be by ethics committees. 7 8 9 Benefits: You will receive only transport allowance as a compensation for the time you will spend for 10 11 interview. Your participation is very important for us to find the answer to the research question which in 12 turn benefits the society especially women and their families. 13 14 15 Risks: The study has no risk for the participants and interviews will be conducted in privacy, dedicated 16 office for the study. For peer review only 17 18 19 Inducement, incentive and Compensation: This study process has no any form of inducement, coercion 20 and the study does not bring any risks that incur compensation. 21 22 23 Results Dissemination: The researcher is responsible for dissemination of findings in different seminars 24 25 and conferences. Moreover, maximum effort will be done to publish the finding in scientific reputable 26 journal. 27 28 29 Right to Refuse or Withdraw: You do not have to take part in this research if you do not wish to do so 30 and refusing to participate will not affect your treatment at this hospital or clinic in any way. You will still 31

32 have all the benefits that you would otherwise have at this clinic or hospital. You may stop participating in http://bmjopen.bmj.com/ 33 34 the research at any time that you wish without losing any of your rights as a patient here. Your treatment at 35 this clinic will not be affected in any way. 36 37 38 Person to Contact: You have the right to ask information that is not clear about the research context and 39 content before and or during the research work. If you have any questions, you may ask or contact to the 40 on September 25, 2021 by guest. Protected copyright. 41 persons stated below. You can contact them any time, even after the study has started. If you wish to ask 42 questions later, you may contact the investigator at the following address; 43 44 If you have any further question and in case of urgency you can contact 45 46 Dr. Adamu Addissie (0115547319; E-mail [email protected]) 47 Dr. Mathewos Assefa (0911240521; E-mail [email protected]) 48 49 Mr. Alem G.mariam (0910352915; E-mail [email protected]) 50 51 Institutional Review Board 52 53 Address Addis Ababa University, College of Health Sciences 54 Telephone +251-115538734 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 26 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Part II. Consent form 4 I, the undersigned, confirm that, as I give consent to participate in the study, it is with a clear 5 6 understanding of the objectives and conditions of the study & with recognition of my right to withdraw 7 from the study if I change my mind. 8 9 I ______do herby give consent to Mr. /Mrs./Miss 10 11 ______to include me in the proposed research. I have been given the 12 necessary information about the research. I have also been assured that I can withdraw my consent at any 13 14 time without penalty or loss of benefits. The proposal has been explained to me in the language I 15 understand. 16 For peer review only 17 Are you willing to participate in the study? 18 Yes No (Terminate the interview and say 19 20 thank you) 21 22 Patients contact Address (mobile) 23 Participants Mobile No. ______24 25 Family/partner Mobile No. ______26 27 Name of interviewer Dr/ Mr. /Mrs./Miss ______Date _____/_____ / _____ 28 29 30 Supervisor 31 Dr/ Mr. /Mrs./Miss ______signature ______Date ___ / ___ /____ 32 http://bmjopen.bmj.com/ 33 BREAST CANCER PATIENT SURVEY - I 34 Questionner ID. ______35 36 Date of interview: _____/_____/______37 38 Patient’s Medical Record Number 39 ______40 Pathology Number: ______Facility Pathology performed: ______on September 25, 2021 by guest. Protected copyright. 41 42 Date of Pathology result received: ___/______/ ______43 44 45 Name of the Health facility______Department: ______46 47 Participant Address 48 49 Sub-city: ______District: ______House No. ______50 51 Participant’s phone number: ______52 53 Identification of proxy 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 27 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 1. If you had to choose, which person would you say knows best how you are doing since your cancer 4 5 diagnosis? So that we may contact them in the future, may I have their phone number? 6 I. ______phone number______R/nship ______7 8 II. ______phone number______R/nship ______9 10 III. ______phone number______R/nship ______11 2. If, in the future if we are unable to reach you, may we have your permission to speak with any of 12 13 these persons to find out how you are doing? 14 0- No 15 16 1- Yes For peer review only 17 1. Socio-demographic characteristics of participant 18 19 20 Q.No. Questions Choices Remarks 21 101. How old are you? (age in years) Enter ______22 23 102. What is your ethnicity? ______24 25 103. What is your religion? 1. Christians 26 2. Islam 27 88. Others, specify ______28 104. Participants highest level of 1. Can’t read and write 29 education obtained 2. Can read and write 30 3. Elementary (Grade, 1-8th) 31 4. Secondary (Grade, 9-12th) 32 5. Diploma http://bmjopen.bmj.com/ 33 6. Bachelor’s Degree 34 7. Masters and above 35 36 105. Participant’s occupation 1. Housewife 37 2. Government employee 38 3. Private employee 39 4. Merchant

40 5. Daily labourer on September 25, 2021 by guest. Protected copyright. 41 6. Student 42 7. Pensioned 43 88. Other (specify)______44 45 106. What is your current marital status? 1. Married 46 2. Single 47 3. Divorced Q109 48 4. Separated 49 88. Others, specify______50 107. Partner’s educational level 1. Can’t read and write 51 2. Can read and write 52 3. Elementary (Grade, 1-8th) 53 4. Secondary (Grade, 9-12th) 54 5. Diploma 55 6. Bachelor’s Degree 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 28 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 7. Masters and above 4 5 108. Partner’s occupation? 1. Government employee 6 2. Private employee 7 3. Daily labourer 8 4. Merchant 9 5. Student 10 6. Has no job 11 7. Pensioned 12 88. Other (specify)______13 109. Number of individuals that live in ______(number) 14 15 your house hold including yourself 16 For peer review only 17 110. Including income provided by you, 1. 600 birr and above 18 your spouse and others you regard 2. 601 - 1,650 birr 19 as a family who live in your 3. 1,651 - 3,200 birr 20 household, what was your total 4. 3,201 - 5,250 birr 21 average monthly household income 5. 5,251 - 7,800 birr 22 (from all sources) 6. 7,801 - 10,900 birr 23 24 7. More than 10,900 birr 25 111. How do you pay your medical care 1. Out of pocket go to 26 expenses? 2. Free medical care Q113 27 3. Government insurance 28 4. Private insurance 29 5. Employing organization 30 112. What percent of your medical 31 expense is covered by the

32 insurance? ______% http://bmjopen.bmj.com/ 33 34 113. Have you ever give birth? 0- No Q. 201 35 1- Yes 36 114. How many children do you have? ______(number) 37 38 115. How old were you when you had ______years 39 your first child? 40 on September 25, 2021 by guest. Protected copyright. 41 42 43 2. Participants’ lifestyle and medical condition 44 45 Q. Questions Choices Remark 46 47 N 48 201. Do you have any medically confirmed 0. No Q. 203 49 chronic medical conditions? 1. Yes 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 29 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 202. Which of medical conditions do you No Yes 4 have? (multiple Reponses possible) 1. Diabetes 0 1 5 2. Hypertension 0 1 6 Read each of listed diseases 3. Heart disease 0 1 7 4. Tuberculosis 0 1 8 9 5. Kidney disease 0 1 10 88. Others specify ______11 A. ______12 B. ______13 C. ______14 15 203. Have any of your relatives ever been 0. No Q. 205 16 diagnosed withFor breast cancer?peer review1. Yes only 17 99. Refused 18 100. I do not know 19 204. If yes, relationship with the patient? 1. Mother 20 21 Check all that apply 2. Sister 22 88. Others, specify______23 24 205. Have you ever smoked cigarettes? 0. No Q. 209 25 1. Yes 26 206. For how long do you ever smoked? ______months/years 27 207. Do you smoke cigarettes regularly now? 0. No Q. 209 28 29 1. Yes 30 208. On average, how many cigarettes do you ______# cigarettes per day 31 smoke per day? (1pack = 20 cigarettes)

32 99. Refused http://bmjopen.bmj.com/ 33 100. Don’t know 34 209. In the year before your diagnosis with 0. No Q. 212 35 36 CANCER, have you ever drunk any type 1. Yes 37 of alcoholic beverage? 38 210. Do you have habit of drinking alcohol 0. No Q. 212 39 currently 1. Yes 40 on September 25, 2021 by guest. Protected copyright. 41 99. Refused 42 211. On average, how many drinks do you ______bottle 43 have per day? 99. refused 44 100. I do not know 45 212. Weight of the participant in KG ______kilograms 46 47 213. Height of the participants in cent meters ______Cent Meters 48 without shoes? 49 50 51 3. Pre-Diagnosis History of participants 52 53 Q. N Question Choices Remark 54 55 301. Have you ever heard of breast cancer 0. No Q. 303 56 prior to your first symptom 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 30 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 1. Yes 4 5 302. If so, how did you learn about breast 1. Mass media (TV, radio, internet) 6 cancer? 2. Healthcare provider 7 (multiple answers are possible) 3. Friend/family/neighbours 8 (Read the options) 88. Other specify: ______9 Do you know how to examine your 0. No 10 303. breasts using your hand for lumps? 1. Yes 11 12 304. Before you feel/saw the symptom/sign 0. No 13 of your breast problem, did you ever 1. Yes 14 examine your breast using your hand for 15 lumps? 16 For peer review only 17 305. Before you feel/saw the symptom/sign 0. No 18 of your breast problem, did a doctor or 1. Yes 19 nurse ever examine your breast for 20 lump? 21 306. Before you feel/saw the symptom/sign 0. No 22 of your breast problem, did you have a 23 1. Yes 24 mammogram (a machine to look for a 25 lump or other abnormalities in your 26 breast)?

27 307. On what day did you first noticed the ____/ _____/ ______dd/mm/yyyy 28 problem with your breast? 29 (pleas identify any information that the 30 patient can provide, whether a full date, 31 a month and year, or the year only) 32 308. If you do not remember the month, but 1. Beginning http://bmjopen.bmj.com/ 33 remember the year, was it the 2. Middle 34 beginning, middle, or end of the year? 35 3. End 36 4. Don’t know the year 37 38 309. What was the symptom you first 1. Breast pain 39 noticed? 2. Breast Mass

40 3. Nipple discharge on September 25, 2021 by guest. Protected copyright. Multiple response is possible 41 Read the options 4. Skin changes 42 88.Other, specify: ______43 44 310. Were you pregnant when you first 0. No 45 developed this symptom? 1. Yes 46 47 311. Were you breastfeeding when you first 0. No 48 developed the symptom? 1. Yes 49 50 312. Who discovered the symptom? 1. Self 51 2. Husband 52 3. Healthcare provider 53 88. Others, specify 54 ______55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 31 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 313. What was your immediate 1. Mich 4 impression/suspicion to the first 2. Tumor 5 symptom? 6 3. Cancer 7 4. Nothing 8 88. other, specify ______9 314. What was your immediate action to the 1. I did nothing 10 first symptom? 11 2. I went to health facility immediately 12 3. I went to traditional healers 13 4. I performed ritual activities 14 88. Others, specify ______15 315. Did you see a traditional healer first for 0. Yes 16 For peer review only 17 your symptom? 1. No Q317 18 99. Refused 19 316. If yes, can you describe it? ______20 ______21 22 ______23 ______24 317. Were there any ritual activities that you 0. Yes 25 have done for your symptom as a 1. No 26 treatment? 99. Refused Q319 27 28 318. If yes, can you tell me what you did? 1. Holly water 29 2. Praying 30 Multiple response possible 88. Others, specify 31 Read the options 32 http://bmjopen.bmj.com/

33 319. When was the first time you visited a ____/_____/_____ dd/mm/yyyy 34 health facility for your cancer? 35

36 320. If you do not remember the month, but 1. Beginning 37 remember the year, was it the 38 2. Middle beginning, middle, or end of the year? 39 3. End

40 4. Don’t know the year on September 25, 2021 by guest. Protected copyright. 41 321. Which level of health facility did you 1. Health center 42 first visit for your problem? 2. Public Hospital 43 3. Private hospital 44 4. Private clinic______45 Did you experience additional 0. No Q. 324 46 322. 47 symptoms before you went to healthcare 1. Yes 48 provider? 49 323. If yes, what were the additional 1. Pain 50 symptoms you experienced? 2. Lumps 51 3. Itching or burning 52 Multiple response possible 4. Nipple discharge 53 Read options 88. Other, Specify: ______54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 32 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 324. What motivated (triggered) you to see a 1. First symptom 4 healthcare provider for your symptom? 2. Additional symptoms 5 3. Family member 6 4. Friend 7 5. A provider secondary to other care 8 9 88. Other, Specify______10 325. When was the time biopsy taken for ____/ ____/______(dd/mm/yyyy) 11 confirmation of your breast problem? 12 13 326. How many health facilities did you ______health facilities 14 visited before you received a final 15 diagnosis for your problem? 16 For peer review only 17 327. How many times did you go to a health ______times 18 facility before you received a final 19 diagnosis for your problem? 20 21 For women who delayed more than three months prior to seeking medical care at a health center or 22 hospital (if not end survey one) 23 24 328. What was the single most ______25 important factor that prevented ______26 you from seeking medical care 27 sooner? 28 29 329. Did any of the following 1. I wasn’t bothered by the problem at first 30 prevent you from seeking 2. I was too busy at home or at my job 31 medical care at a health center 3. I was afraid of being examined by a doctor 32 http://bmjopen.bmj.com/ 33 or hospital sooner? or other health provider 34 Read the choices and circle all 4. I was afraid of examination results 35 that apply 5. I was afraid of the treatments, including 36 potentially losing my breast 37 38 6. I visited a traditional healer first 39 7. I didn’t know where an appropriate

40 medical facility was on September 25, 2021 by guest. Protected copyright. 41 8. I didn’t want anyone knowing I had a 42 breast problem 43 44 9. I thought treatment might be too expensive 45 88. Other, specify: 46 ______47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 33 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4.Patients Reported Outcome 4 5 4.1. Participants’ experience of cancer related pain 6 7 The following questions ask about any physical pain you may experience from your cancer within the last 4 8 weeks. This includes pain from surgery for cancer, pain from cancer treatments (chemotherapy or radiation), 9 or pain from the disease itself. Please remember to answer these questions about cancer related pain only 10 11 12 S.N Question Response Remarks 13 14 1. Do you have any pain from your cancer 0. No If “No” skip to 4.2 15 and /or its treatment, even if it was 1. Yes 16 mild? For peer review only 17 2. If yes, what is the source of your pain? 1. Lesion in the cancer cite 18 2. The surgical procedure 19 3. Drug side effect 20 88. Other; specify______21 22 3. During the past 4 weeks, how would you 1. Very Severe 23 rate your severity of pain? 2. Severe 24 3. Moderate 25 4. Mild 26 27 4. Have you taken medicine (prescribed or 0. No If “No” skip to Q5 28 over the counter) to relieve your pain? 1. Yes 29 30 31 5. If yes, how often do you take the 1. less than once a week

32 medicine? 2. once a week http://bmjopen.bmj.com/ 33 3. twice a week 34 4. 3 or more times a week 35 36 6. How much did pain interfere with your 0. Not at all 37 normal work (both outside and in the 1. A little 38 home) 39 2. Quite a bit

40 3. Very much on September 25, 2021 by guest. Protected copyright. 41 42 7. Did you have any pain in your arm or 0. Not at all 43 shoulder? 1. A little 44 2. Quite a bit 45 46 3. Very much 47 48 8. Did you have a swollen arm or hand? 0. Not at all 49 1. A little 50 2. Quite a bit 51 3. Very much 52 53 9. Was it difficult to raise your arm or to 0. Not at all 54 move it sideways? 55 1. A little 56 2. Quite a bit 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 34 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 3. Very much 4 5 6 7 10. Have you had any pain in the area of your 0. Not at all 8 affected breast? 1. A little 9 2. Quite a bit 10 3. Very much 11 12 11. Was the area of your affected breast 0. Not at all 13 14 swollen? 1. A little 15 2. Quite a bit 16 For peer review3. Very much only 17 18 12. Have you had skin problems on or in the 0. Not at all 19 area of your affected breast (e.g., itchy, 1. A little 20 21 dry, flaky)? 2. Quite a bit 22 3. Very much 23 24 25 4.2. Participants Cancer related Fatigue 26 27 The following questions ask about any fatigue you may experience from your cancer within the last 4 28 weeks. This may be resulted from surgery for cancer, pain from cancer treatments (chemotherapy or 29 radiation), or the disease itself. Please remember to answer these questions about cancer related fatigue 30 only 31 32 S. N Question Response Remarks http://bmjopen.bmj.com/ 33 34 1. Over the past 4 weeks, has there been at least a 2 week 0. No If No skip to 35 period when you had significant fatigue, a lack of energy, or 1. Yes 4.3 36 an increased need to rest every day or nearly every day 37 38 39 2. Do you feel weak all over or heavy all over? 0. No

40 1. Yes on September 25, 2021 by guest. Protected copyright. 41 3. Do you have trouble concentrating or paying attention 0. No 42 1. Yes 43 4. Do you have losing your interest or desire to do things you 0. No 44 usually do 1. Yes 45 46 5. Do you have trouble falling asleep, staying asleep, or 0. No 47 waking too early 1. Yes 48 49 6. Do you find yourself sleeping too much compared to what 0. No 50 you usually sleep 1. Yes 51 52 7. Have you found that you usually do not feel rested or 0. No 53 refreshed after you have slept 1. Yes 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 35 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 8. Do you have to struggle or push yourself to do anything 0. No 4 1. Yes 5 6 9. Did you find yourself feeling sad, frustrated, or irritable 0. No 7 because you felt fatigue? 1. Yes 8 9 10. Did you have difficult finishing something you had started 0. No 10 to do because of feeling fatigued? 1. Yes 11 12 11. Did you have trouble remembering things? For example, did 0. No 13 you have trouble remembering where your keys were or 1. Yes 14 what someone had told you a little while ago? 15 16 For peer review only 17 12. Did you find yourself feeling sick or unwell for several 0. No 18 hours after you had done something that took some effort? 1. Yes 19 20 13. Has fatigue made it hard for you to do your work, take care 0. No 21 of things at home, or get along with other people? 1. Yes 22 23 24 4.3. Depression 25 26 Over the past 2 weeks, how often have you been bothered by any of the following problems? 27 Instruction: Several days (2-6 days), more than half of the days (7-11days), nearly every day (12-14days) 28 S.N About your feeling (PROBLEMS WITH…) Response Remarks 29 1. Does your interest or pleasure in doing things was 0-No GO TO Q 2 30 decreased so much 1-Yes 31

32 How often do you felt over the last two weeks? 1-several days http://bmjopen.bmj.com/ 33 2-Morethan half of the days 34 3-Nearly every day 35 2. Feeling down, depressed or hopeless 0-No GO TO Q 3.1 36 1-Yes 37 How often do you felt over the last two weeks? 1-several days 38 2-Morethan half of the days 39 3-Nearly every day 40 3.1 Trouble failing asleep or staying asleep 0-No GO TO Q 3.2 on September 25, 2021 by guest. Protected copyright. 41 1-Yes 42 43 How often do you felt over the last two weeks? 1-several days 44 2-Morethan half of the days 45 3-Nearly every day 46 3.2 Trouble by a sleeping too much 0-No GO TO Q 4 47 1-Yes 48 How often do you felt over the last two weeks? 1-several days 49 2-Morethan half of the days 50 3-Nearly every day 51 4. Feeling tired or having little energy 0-No GO TO Q 5.1 52 1-Yes 53 How often do you felt over the last two weeks? 1-several days 54 55 2-Morethan half of the days 56 3-Nearly every day 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 36 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 5.1 Poor appetite 0-No GO TO Q 5.2 4 1-Yes 5 How often do you felt over the last two weeks? 1-several days 6 7 2-Morethan half of the days 8 3-Nearly every day 9 5.2 Overeating 0-No GO TO Q 6 10 1-Yes 11 How often do you felt over the last two weeks? 1-several days 12 2-Morethan half of the days 13 3-Nearly every day 14 6. Feeling bad about yourself-or that you are a failure or 0-No GO TO Q 7 15 have let yourself or your family down 1-Yes 16 How often do youFor felt over peerthe last two weeks? review 1 -onlyseveral days 17 2-Morethan half of the days 18 3-Nearly every day 19 7. Trouble concentrating on things, such as reading the 0-No GO TO Q 8.1 20 newspaper or watching television 1-Yes 21 22 How often do you felt over the last two weeks? 1-several days 23 2-Morethan half of the days 24 3-Nearly every day 25 8.1 Moving or speaking so slowly that other people could 0-No GO TO Q 8.2 26 have noticed 1-Yes 27 How often do you felt over the last two weeks? 1-several days 28 2-Morethan half of the days 29 3-Nearly every day 30 8.2. Moving or speaking so loudly, fidgety or restless that 0-No GO TO Q 9 31 you have been moving around a lot more than usual that 1-Yes 32 other people could have noticed http://bmjopen.bmj.com/ 33 How often do you felt over the last two weeks? 1-several days 34 2-Morethan half of the days 35 3-Nearly every day 36 9 Thoughts that you would be better off dead or of hurting 0-No 37 38 yourself in some way 1-Yes 39 How often do you felt over the last two weeks? 1-several days

40 2-Morethan half of the days on September 25, 2021 by guest. Protected copyright. 41 3-Nearly every day 42 10. If you checked off (Q1-9) any problems, how difficult 0. Not difficult at all 43 have those problems made it for you to do your work, 1. Somewhat difficult 44 take care of things at home, or get along with other 2. Very difficult 45 people? 3. Extremely difficult 46 47 4.4 . Participants Sleep disorder 48 49 The following questions ask about any trouble Sleeping you may experience from your cancer within 50 the last 4 weeks. This may be resulted from surgery for cancer, pain from cancer treatments 51 (chemotherapy or radiation), or the disease itself. Please remember to answer these questions about 52 cancer related sleep disorder only 53 54 S.N Question Response Remarks 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 37 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 1. During the last 4 weeks, have you ever 1. Yes If “No skip” to 4.5 4 had trouble sleeping because of your 2. No 5 cancer 6 7 2. If yes, what do you think the reason of 1. Pain from the Lesion of 8 the cancer cite 9 your trouble sleep? 10 2. The surgical procedure 11 3. Drug side effect 12 4. Fear of metastasis 13 88. Other; specify______14 3. Have you taken medicine (prescribed or 0- No If “No” skip to Q6 15 over the counter) to help you sleep? 1- Yes 16 For peer review only 17 4. If yes, how often do you take the 1.less than once a week 18 medicine? 2. 1 to 2 times a week 19 3. 3 to 5 times a week 20 4. Daily 21 22 23 4.5. Physical activity of the participants 24 The following questions ask about any trouble in physical activities, and day to day work you may 25 experience from your cancer within the last 4 weeks. 26 27 1 About your Health and Activities Never Almost Never Some- Often Almost 28 (PROBLEMS WITH…) times Always 29 30 1.1 Have you felt hard to walk a 0 1 2 3 4 31 distance of more than one bus

32 terminal? http://bmjopen.bmj.com/ 33 1.2 Have you had difficulty to lift 0 1 2 3 4 34 something heavy? 35 1.3. Have you had difficulty to take a 0 1 2 3 4 36 bath or shower by yourself? 37 The following three questions are to participants who have a job or student. If the participant 38 has no outdoor job or she is not student go to section part 5 39 2 About your Work/Studies Never Almost Never Some- Often Almost 40 (PROBLEMS WITH…) times Always on September 25, 2021 by guest. Protected copyright. 41 2.1 I have trouble keeping up with my 0 1 2 3 4 42 work or studies 43 44 2.2 Have you had missed work or 0 1 2 3 4 45 school because of not feeling well? 46 2.3 Have you had missed work or 0 1 2 3 4 47 school to go to the doctor or 48 hospital? 49 50 51 Part 5. Address the following questions by measuring appropriately 52 53 54 1 Weight of the respondent (please measure her weight _____ kg 55 appropriately) 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 38 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 2 Height of the participant (please measure her weight ______cent meter 4 5 appropriately) 6

7 8 Thank you for your time!! 9 10 11 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 39 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Breast Cancer Patient Survey - II 4 5 Questionner ID. ______Date of interview: _____/_____/______6 7 Patient’s Medical Record No. ______Participant’s phone number: ______8 9 Primary relative’s phone number: ______relationship: ______10 11 12 Name of interviewer: Dr/ Mr. /Mrs./Miss: ______Date: _____/_____ / _____ 13 14 15 Supervisor: 16 Dr/ Mr. /Mrs./Miss: ______For peer review signature: ______only Date: ___ / ___ /____ 17 18 19 2. 1. Treatment status of BC patients 20 Q. N Statements Choices Remarks 21 101. Have you received any treatment for 0. No Q204 22 you cancer? 1. Yes 23 24 102. If yes, what kind of treatments you 1. Surgery to remove the cancer 25 have received? 2. Chemotherapy 26 (multiple answer is possible) 3. Radiation therapy 27 4. Hormone therapy 28 29 88. Other forms of treatment; specify: 30 ______31 103. Where (in which facility) did you 32 receive these treatments? http://bmjopen.bmj.com/ 33 34 35 104. Since you were diagnosed with the 0. No Q201 36 disease, were you unable to receive 1. Yes 37 any form of treatments 38 39 105. What was the main reason for you 1. Could not afford the price of the 40 not receiving the treatment? treatment on September 25, 2021 by guest. Protected copyright. 41 2. Treatment not locally available 42 Multiple response is possible 3. Waited too long to get it 43 4. Difficulty in getting appointments 44 45 5. Do not like or trust or believe in 46 doctors 47 6. Insurance did not cover 48 7. Did not know where to go for 49 treatment 50 88. Others; specify ______51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 40 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 2.2. Participants practice of traditional medicine to treat or relieve the symptoms of their CANCER 4 (after they have diagnosed) 5 S.N Question Choices Remark 6 7 201. Have you seen a traditional healer other 0. No Q301 8 than your regular doctors? 1. Yes 9 202. If yes, what type of healer did you see? 1. Herbalist 10 2. Spiritual healer 11 88. Other, specify 12 ______13 203. What is your main reason for using this 1. To treat my cancer 14 therapy? 2. To lessen the side effects of 15 cancer treatment 16 Multiple answerFor is possible peer review3. To relieve symptomsonly of my 17 18 cancer 19 4. To relieve stress 20 88. Other: specify: 21 ______22 204. How much would you estimate your or ______birr 23 your family have been spending per 24 month for these healers/ herbs/ or other 25 therapies? 26 27 205. Is your doctor aware that you are using 0. No 28 this therapy? 1. Yes 29 99. I do not know 30 31

32 2.3. Participants adherence to chemotherapy and hormonal therapy http://bmjopen.bmj.com/ 33 S. N Questions Choices Remarks 34 301. Have you taken chemotherapy? 0. No Q 305 35 1. Yes 36 302. If yes, how many cycles did your doctor ______number 37 38 ordered? 99. I do not know 39 303. Did you finish all the cycles? 0. No

40 1. Yes Q305 on September 25, 2021 by guest. Protected copyright. 41 304. 1. I forget to keep treatment appointments 42 If no, what are the main reasons? 2. I could not tolerate the side effects 43 3. I could no longer afford the treatment 44 4. I did not trust the effectiveness of the 45 medicine 46 5. The drug was not available 47 2. Others, specify 48 ______49 305. Are you taking hormonal therapy? 0. No Q 401 50 1. Yes 51 306. ______52 For how long did your doctor tell you to 53 take the drug? 54 307. Have you ever missed taking your 0. No Q401 55 hormonal therapy? 1. Yes 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 41 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 308. ______times 4 If yes, how often you missed? 5 6 309. If yes, for how long you missed? ______7 8 310. What was your main reason for missing 1. Side-effects 9 taking the drug? 2. Financial 10 3. Drug not available 11 12 4. I forget to take 13 88. Others, specify 14 ______15 16 2.4. Participants historyFor of medical peer cost for cancerreview treatment only 17 Q.N Question Choices Remark 18 19 401. Do you have any health insurance that covers your 0. No Q403 20 medical expense? 1. Yes 21 402. If yes, how much percent of your medical expense ______% 22 is covered by insurance 23 403. Do you have free medical service card? 0. No Q406 24 1. Yes 25 404. Were there any tests or treatments (including 0. No Q406 26 prescription medication for treatment or side 1. Yes 27 28 effects) that your doctor recommended for cancer 29 that your free service card did not cover? 30 405. What were the services you did not get for free? 1. ______31 Multiple response possible 2. ______

32 3. ______http://bmjopen.bmj.com/ 33 406. Because of your cancer, its treatment or the lasting 1. Medical expenses (medicine, 34 effects of that treatment, did you have any costs medical equipment) 35 you had to pay out of your own pocket in the 2. Transportation 36 following categories? 3. I had no out-of-pocket costs 37 Multiple response possible 4. I do not know/I am not sure 38 88. Others: Specify 39 ______40 on September 25, 2021 by guest. Protected copyright.

41 42 407. Can you estimate your out-of-pocket cost? 0. No Q409 43 1. Yes 44 408. If yes, how much? 1. Diagnosis ______Br 45 2. Treatment ______Br 46 3. Follow up ______Br 47 409. Were there any tests or treatments that your doctor 0. No Q411 48 recommended for your CANCER that you did not 1. Yes 49 get because you were unable to pay for them? 50 410. What tests or treatments were those? SPECIFY 1.______51 (FREE TEXT) 2.______52 3.______53 411. Have you ever forced to sell your property for 0- No Q413 54 covering the medical cost of cancer treatment, or 1- Yes 55 lasting effects of treatment 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 42 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 412. If yes, what type of property did you sell? 4 ______5 6 7 413. Have you or has anyone in your family had to 0. No Q415 8 borrow money or go into debt because of your 1. Yes 9 cancer, its treatment, or the lasting effects of that 10 treatment? 11 414. How much did you or your family borrow, or how ______birr 12 much debt did you incur because of your cancer, its 13 treatment, or the lasting effects of that treatment? 14 415. What is your average cost you spend per month for ______Birr 15 transportation related to your cancer? 16 416. Have you ever worriedFor about peer your family’s review 0. No only 17 financial stability because of your cancer, its 1. Yes 18 treatment or lasting effects of that treatment? 19 417. What is your current employment situation? Choice 1. Full time employed 20 21 only one 2. Part-time employed 22 3. Self-employed 23 4. On leave with pay 24 5. On leave without pay 25 6. Not employed-disabled 26 7. Retired 27 8. Homemaker 28 88. Others; specify ______29 418. Were you employed, when you were diagnosed with 0. No Q427 30 cancer? 1. Yes 31 419. At any time since your first cancer diagnosis, did 0. No Q427 32 you take extended paid time off from work, unpaid 1. Yes http://bmjopen.bmj.com/ 33 time off, or make a change in your hours, duties or 34 employment status? 35 420. When did you take extended paid time off from 1. At the time of diagnosis 36 work? 2. During treatment 37 38 Multiple response possible 3. After treatment 39 421. Did you ever change from working full-time to 0. No

40 working part-time or change to a less demanding 1. Yes on September 25, 2021 by guest. Protected copyright. 41 job? 42 422. Did you ever change from a set work schedule, 0. No 43 where you start and end at the same time every day, 1. Yes 44 to a flexible work schedule, where your start and end 45 times vary from day-to-day? 46 423. Because of your cancer, its treatment, or its lasting 0. No 47 effects, did you ever decide not to pursue an 1. Yes 48 advancement or promotion? 49 424. Because of your cancer, its treatment, or its lasting 0. No 50 effects, did you retire earlier than you had planned? 1. Yes 51 425. Did you lose any earning as a consequence of your 0. No Q427 52 cancer diagnosis? 1. Yes 53 54 426. If yes, how much money do you lost per month ______Birr 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 43 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 427. Since the time you were first diagnosed with cancer, 0. No Q501 4 has any friend or family member provided care to 1. Yes 5 you during or after your cancer treatment? 6 428. Who was your caregiver? 1. Spouse/partner 7 2. Child 8 9 3. Sibling 10 4. Parent 11 5. Other relative 12 6. Friend 13 88. Other, specify - 14 ______15 429. Because of your cancer, its treatment, or the lasting 0. No Q501 16 effects of that treatment,For didpeer any of your reviewcaregivers 1. onlyYes 17 ever take extended paid time off from work, unpaid 2. None of my caregivers were 18 time off, or make a change in their hours, duties or employed 19 employment status? 99. I do not know 20 430. If yes how much money did he/she lost per month? ______Birr 21 431. Did any of your caregivers ever take extended paid 0. No 22 time off from work, unpaid time off, or make a 1. Yes 23 change in their hours, duties, or employment status 99. I do not know 24 for at least 2 months? 25 26 27 2.5. Cancer patients’ survivorship care 28 S.N Question Choices Remarks 29 501. Do you have a regular follow-up? 0. No 30 1. Yes 31 502. Did your doctor tell you to have a 0. No 32 regular follow-up? 1. Yes http://bmjopen.bmj.com/ 33 503. Since your cancer diagnosis, has your 1. Dietician or nutritionist 34 doctor or a member of your health 2. Physical and or occupational therapist 35 care team ever referred you to any of 3. Mental health professional (psychiatrist, 36 the following specialties? psychologist, marriage or family therapist) 37 38 Mark all that apply 4. Social worker 39 5. Spiritual counselor

40 6. I have never been referred to any health specialists on September 25, 2021 by guest. Protected copyright. 41 88. Other specify ______42 504. Since your cancer diagnosis, have 1. Screening for cervical cancer 43 you had any of the following cancer 2. Mammogram for breast lump 44 screening tests? 3. I did not have it 45 Mark all that apply 88. Other specify: ______46 47 2.6. Depression 48 Over the past 2 weeks, how often have you been bothered by any of the following problems? 49 Instruction: Several days (2-6 days), more than half of the days (7-11days), nearly every day (12-14days) 50 S.N About your feeling (PROBLEMS WITH…) Response Remarks 51 1. Does your interest or pleasure in doing things was 0-No GO TO Q 2 52 decreased so much 1-Yes 53 54 How often do you felt over the last two weeks? 1-several days 55 2-Morethan half of the days 56 3-Nearly every day 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 44 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 2. Feeling down, depressed or hopeless 0-No GO TO Q 3.1 4 1-Yes 5 How often do you felt over the last two weeks? 1-several days 6 2-Morethan half of the days 7 3-Nearly every day 8 9 3.1 Trouble falling asleep or staying asleep 0-No GO TO Q 3.2 10 1-Yes 11 How often do you felt over the last two weeks? 1-several days 12 2-Morethan half of the days 13 3-Nearly every day 14 3.2 Trouble by a sleeping too much 0-No GO TO Q 4 15 1-Yes 16 How often do youFor felt over peerthe last two weeks? review 1 -onlyseveral days 17 2-Morethan half of the days 18 19 3-Nearly every day 20 4. Feeling tired or having little energy 0-No GO TO Q 5.1 21 1-Yes 22 How often do you felt over the last two weeks? 1-several days 23 2-Morethan half of the days 24 3-Nearly every day 25 5.1 Poor appetite 0-No GO TO Q 5.2 26 1-Yes 27 How often do you felt over the last two weeks? 1-several days 28 2-Morethan half of the days 29 3-Nearly every day 30 5.2 Overeating 0-No GO TO Q 6 31 1-Yes 32 http://bmjopen.bmj.com/ 33 How often do you felt over the last two weeks? 1-several days 34 2-Morethan half of the days 35 3-Nearly every day 36 6. Feeling bad about yourself-or that you are a failure or 0-No GO TO Q 7 37 have let yourself or your family down 1-Yes 38 How often do you felt over the last two weeks? 1-several days 39 2-Morethan half of the days

40 3-Nearly every day on September 25, 2021 by guest. Protected copyright. 41 7. Trouble concentrating on things, such as reading the 0-No GO TO Q 8.1 42 newspaper or watching television 1-Yes 43 How often do you felt over the last two weeks? 1-several days 44 2-Morethan half of the days 45 3-Nearly every day 46 8.1 Moving or speaking so slowly that other people could 0-No GO TO Q 8.2 47 48 have noticed 1-Yes 49 How often do you felt over the last two weeks? 1-several days 50 2-Morethan half of the days 51 3-Nearly every day 52 8.2. Moving or speaking so loudly, fidgety or restless that 0-No GO TO Q 9 53 you have been moving around a lot more than usual that 1-Yes 54 other people could have noticed 55 How often do you felt over the last two weeks? 1-several days 56 2-Morethan half of the days 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 45 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 3-Nearly every day 4 9. Thoughts that you would be better off dead or of hurting 0-No GO TO Q 10 5 yourself in some way 1-Yes 6 How often do you felt over the last two weeks? 1-several days 7 8 2-Morethan half of the days 9 3-Nearly every day 10 10. If you checked off (Q1-9) any problems, how difficult 4. Not difficult at all 11 have those problems made it for you to do your work, 5. Somewhat difficult 12 take care of things at home, or get along with other 6. Very difficult 13 people? 7. Extremely difficult 14 15 Is there anything else you would like to tell us about your experiences with cancer?” 16 For peer review only 17 18 ______19 ______20 21 22 Thank you for participating in this important study! 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from

Breast and cervical cancer patients’ experience in Addis Ababa city, Ethiopia: A follow-up study protocol

Journal: BMJ Open ManuscriptFor ID peerbmjopen-2018-027034.R2 review only Article Type: Protocol

Date Submitted by the 02-Mar-2019 Author:

Complete List of Authors: Gebremariam, Alem; Adigrat University, Public Health Addissie, Adamu; Addis Ababa University School of Public Health, Preventive Medicine Worku, Alemayehu; Addis Ababa University, School of Public Health Hirpa, Selamawit; Addis Ababa University School of Public Health Assefa, Mathewos ; Addis Ababa University School of Medicine, Oncology Pace, Lydia; Brigham and Women's Hospital, Boston, Massachusetts Kantelhardt, Eva; Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University, Halle, Germany Jemal, Ahmedin; American Cancer Society, Surveillance and Health Services Research

Primary Subject Oncology http://bmjopen.bmj.com/ Heading:

Secondary Subject Heading: Oncology, Public health, Epidemiology

Breast Neoplasm, Uterine Cervical Neoplasm, Reported Outcome Keywords: Measures, Addis Ababa, Ethiopia

on September 25, 2021 by guest. Protected copyright.

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4 Breast and cervical cancer patients’ experience in Addis 5 6 7 Ababa city, Ethiopia: A follow-up study protocol 8 9 10 11 Alem Gebremariam1,2*, Adamu Addissie2, Alemayehu Worku Yalew2, Selamawit Hirpa2 12 13 Mathewos Assefa3, Lydia E. Pace4, Eva Johanna Kantelhardt5, Ahmedin Jemal6 14 15 1Department of Public Health, College of Medicine and Health Sciences, Adigrat University 16 For peer review only 17 18 Adigrat, Ethiopia 19 20 2School of Public Health, College of Health Sciences, Addis Ababa University, Addis Ababa, 21 22 Ethiopia 23 24 3 25 Department of Radiotherapy Center, School of Medicine, Addis Ababa University, Addis 26 27 Ababa, Ethiopia 28 29 4Brigham and Women's Hospital, Boston, Massachusetts, USA 30 31 5Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University, 32 http://bmjopen.bmj.com/ 33 34 Halle, Germany 35 36 6Surveillance and Health Services Research, American Cancer Society, Atlanta, Georgia, United 37 38 States of America 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 * Corresponding Author: Alem Gebremariam, BSc, MPH 43 44 Addis Ababa University, Ethiopia 45 46 Email: [email protected]; Tel: +251-910352915 47 48 49 Word count=3980 (excluding title page, abstract, Strengths and limitations of this study 50 51 52 References) 53 54 55 56 57 58 1 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 ABSTRACT 4 5 6 7 Introduction: Cancer is an emerging public health problem in Ethiopia, with breast and cervical 8 9 cancers accounting for over half of all newly diagnosed cancers in women. The majority of women 10 11 with breast and cervical cancer are diagnosed at late stage of the disease and most patients do not 12 13 14 receive care consistent with global standards. However, little is known about the health seeking 15 16 behaviors, barriers toFor early detection peer and treatment,review patient reportedonly outcomes, financial burden, 17 18 and survival of women with breast and cervical cancer in the country. Therefore, this study aims 19 20 21 to document the experience of women with breast and cervical cancer from recognition of 22 23 symptoms to diagnosis, treatment, and survivorship/mortality in Addis Ababa city, Ethiopia. 24 25 Methods and analysis: A prospective follow-up study using mixed methods (both quantitative 26 27 28 and qualitative) will be employed. All women newly diagnosed with breast and cervical cancer 29 30 from January 1, 2017 to June 30, 2018 in Addis Ababa will be included in the study. Interviewer 31

32 administered questionnaires will be used to collect information about medical consultations after http://bmjopen.bmj.com/ 33 34 recognition of symptoms, health seeking behaviors, treatment received, barriers to early detection 35 36 37 and treatment, and survivorship care. In-depth interview will be conducted on purposefully 38 39 selected women with breast and cervical cancer. The primary outcomes of the study are time

40 on September 25, 2021 by guest. Protected copyright. 41 intervals (patient and diagnostic waiting times), stage at diagnosis, and survival. Multivariable 42 43 44 analysis will be employed to determine the contributions of independent variables on the outcomes 45 46 of interest. Hazard ratios with 95% confidence intervals will be calculated for time to event 47 48 outcomes. Qualitative data will be analyzed using thematic analysis. 49 50 51 Ethics and dissemination: This protocol is ethically approved by Institutional Review Board of 52 53 Addis Ababa University. Verbal informed consent will be obtained from study participants. 54 55 56 57 58 2 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Results will be disseminated in international peer-reviewed journals and presented in relevant 4 5 6 conferences. 7 8 9 Keywords: Breast Neoplasm, Uterine Cervical Neoplasm, Patient Reported Outcome Measures, 10 11 Addis Ababa, Ethiopia 12 13 14 Strengths and limitations of this study 15 16 For peer review only 17  This study is the first prospective follow-up study in Ethiopia which will allow us to test 18 19 the temporal relationship between the explanatory variables and outcome of the study. 20 21  The study is multicenter study which will recruit incident cases from the major public and 22 23 24 private health facilities in the city so that generalization about women with breast and 25 26 cervical cancer in the city will be possible latter. 27 28  The study will use mixed methods; the qualitative design will help to understand the 29 30 31 patients’ experience in the course of their illness.

32 http://bmjopen.bmj.com/ 33  The retrospective nature of collecting information about dates of symptom recognition, and 34 35 medical consultations might be prone to recall bias. 36 37 38  Under-reporting of time delays and over-reporting of desirable behavior such as self-breast 39

40 examination, and selection bias due to lost to follow-up are anticipated in the study. on September 25, 2021 by guest. Protected copyright. 41 42 43 INTRODUCTION 44 45 46 Breast and cervical cancers are the most commonly diagnosed cancers and the leading causes of 47 48 cancer death among women in Ethiopia and in other parts of sub-Saharan Africa,[1-3] accounting 49 50 51 for about half of all cancer cases and deaths.[4] These cancers have significant public health and 52 53 societal implications not only because they represent more than half of all cancer cases in women 54 55 56 57 58 3 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 but also because they most frequently occur in young or middle age[5, 6] when patients are in the 4 5 6 workforce, raising children, and supporting other family members. 7 8 9 The morbidity and mortality associated with breast and cervical cancer can be mitigated through 10 11 early detection and receipt of evidence-based, high quality care.[7] However, based on limited data, 12 13 a substantial proportion of women with breast and cervical cancer in Ethiopia present with 14 15 16 advanced-stage disease.For For peerinstance, about review 71% of the breast only cancer cases[6] and 84% cervical 17 18 cancer cases[5] in Ethiopia were diagnosed at advanced stage largely because of prolonged patient 19 20 intervals in seeking medical care after recognition of symptoms and provider/health systems 21 22 23 intervals in referral of patients to cancer treatment centers.[8, 9] Further, most women with breast 24 25 and cervical cancer in the country do not receive treatments consistent with the global standard of 26 27 care.[3] 28 29 30 In addition to early detection and receipt of standard treatments, survivorship care is an important 31

32 http://bmjopen.bmj.com/ 33 component of high quality of care across the cancer continuum. This could be assessed through 34 35 Patient Reported Outcomes (PROs) as well as physician ratings of patients’ wellbeing,[10] though 36 37 PROs are found to be better predictors of patients survival and are thought to be more useful for 38 39 making clinical decision about patient management.[10, 11] There is, however, limited 40 on September 25, 2021 by guest. Protected copyright. 41 42 information on barriers to early detection and receipt of and completion of treatment and patient 43 44 reported outcomes among women with breast and cervical cancer in Ethiopia to guide public health 45 46 policies and patient management.[12] 47 48 49 50 Previous studies from Ethiopia have reported limited knowledge about breast and cervical cancer, 51 52 including about prevention, early detection, and treatment, among healthcare professionals[13-16] 53 54 and the general population.[17-27] This limited awareness likely contributes to the high proportion 55 56 57 58 4 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 of disease detected at advanced stage in the country.[5, 6] Notably, there are also studies conducted 4 5 6 on women with breast and cervical cancer.[5, 6, 8, 9, 28-33] Two of the studies[8, 28] examined 7 8 patient or diagnostic interval among women with breast cancer in Ethiopia and found long waiting 9 10 times to initiate medical consultation (average about 18 months). Similarly, Tadesse reported that 11 12 about 30% (56/198 patient) of women with cervical cancer visited 3 or more health facilities before 13 14 15 being referred to Tikur Anbessa Specialized Hospital (TASH), a referral public hospital, for 16 For peer review only 17 cancer-directed treatment and 20% (46) of the patients waited for more than 6 months from first 18 19 health care visit before they were first seen at TASH.[34] 20 21 22 23 The aforementioned studies, however, were limited because of small sample sizes,[8, 28] and 24 25 reliance on data from chart review[6, 28-30] and data were collected from only one hospital, 26 27 TASH, which houses the only radiotherapy center in the country.[5, 6, 8, 28-30, 32] These all 28 29 30 could make them prone to incompleteness and limit their generalizability to elsewhere in Ethiopia. 31

32 Moreover, none of the studies examined the factors contributing to patient and diagnostic intervals, http://bmjopen.bmj.com/ 33 34 patient reported outcomes, the relationship between patient/diagnostic intervals and stage at 35 36 diagnosis as well as its effect on the survival of women with breast and cervical cancer in Ethiopia. 37 38 39 To help address this information gap, we have established a cohort of newly diagnosed breast and

40 on September 25, 2021 by guest. Protected copyright. 41 cervical cancer patients in Addis Ababa, capital city of Ethiopia. This paper describes the protocol 42 43 of the study, the first prospective follow-up study on cancer patients’ experience in the country 44 45 46 and perhaps in Africa. 47 48 49 METHODS 50 51 52 53 Aim of the study 54 55 1. To explore barriers to early diagnosis of women with breast and cervical cancer 56 57 58 5 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 2. To estimate the duration of patient, diagnostic and treatment initiation intervals of women 4 5 6 with breast and cervical cancer 7 8 3. To assess factors associated with patient, diagnostic and treatment initiation time intervals of 9 10 women with breast and cervical cancer 11 12 4. To examine the association between patient/diagnostic interval and stage at diagnosis 13 14 15 5. To determine patient reported outcomes (levels of fatigue, pain, sleep disorder, and 16 For peer review only 17 depression) 18 19 6. To describe treatment patterns and adherence by socio-demographic factors 20 21 22 7. To document survivorship care (e.g., surveillance for recurrence and late effects of treatment) 23 24 8. To estimate the financial burden of breast and cervical cancer on patients and their families 25 26 9. To estimate two-year survival rates and their associations with patient, diagnostic and 27 28 29 treatment initiation intervals, receipt of treatment, socio-demographic factors, financial 30 31 burden, and other patient reported outcomes.

32 http://bmjopen.bmj.com/ 33 34 Study setting 35 36 37 This study will be conducted in the Addis Ababa, which has a population of about 3.5 million.[35] 38 39

40 The city is served by 11 public and 33 private hospitals, 88 public and 6 non-governmental health on September 25, 2021 by guest. Protected copyright. 41 42 centers , and 777 private clinics.[36] According to a national survey, the main health care providers 43 44 for outpatients was government health facilities (77%), followed by private health facilities (20%), 45 46 47 traditional and religious healers (2%), and Non-governmental organization (1%).[37] A 48 49 population-based cancer registry has been in place since 2011 in Addis Ababa, with incident cases 50 51 collected from 20 health facilities including referral hospitals, higher clinics, and diagnostic 52 53 54 centers.[4] Our study will recruit all women with breast and cervical cancer aged >18 years 55 56 diagnosed from January 1, 2017 – June 30, 2018 in 7 major health facilities. Of which, two are 57 58 6 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 public (TASH, and St. Paul Hospital Millennium Medical College) and five are private (United 4 5 6 Vision Medical Services Center, Hallelujah General Hospital, Betezata Hospital, Legehar Hospital 7 8 and Landmark Hospital). These health facilities capture more than 90% of all women with breast 9 10 and cervical cancer reported to the cancer registry in Addis Ababa. Recruitment of the study 11 12 participants has been started on March 20, 2017. 13 14 15 16 Study designs and Forsample size peer review only 17 18 19 The study design is a prospective follow-up study, using mixed methods (both quantitative and 20 21 qualitative). The quantitative component involves both cross sectional and prospective follow-up 22 23 24 study designs, while the qualitative study is phenomenological study. The latter study design will 25 26 help to understand the breast and cervical cancer patients’ experience of their life before and after 27 28 diagnosis, and during the course of treatment.[11] We expect to recruit about 450 breast and 250 29 30 31 cervical cancer patients, based on the number of breast and cervical cases recorded each year in

32 http://bmjopen.bmj.com/ 33 the city over the past two years,[38] and they will be followed for two years. 34 35 36 The adequacy of the above estimated cohort of 450 breast and 250 cervical cancer patients to 37 38 address the stated specific objectives of the study was assessed. For instance, to estimate the 39

40 on September 25, 2021 by guest. Protected copyright. 41 sample size for the second specific objective (duration of patient and diagnostic waiting times), 42 43 we used single population proportion formula. Taking expected proportion (p=31.7%) of patient 44 45 interval (>3 months) from a similar study,[39] 95% confidence level (Zα/2=1.96) and a 5% 46 47 48 precision, a minimum of 333 patients are required for the study. In contrast, the minimum sample 49 50 sizes for the third (factors associated with patient and provider time intervals), fourth (the 51 52 association between patient or provider interval and stage at diagnosis) and ninth specific objective 53 54 55 (survival rate of the patients) were estimated using two population proportion formula assuming 56 57 58 7 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 95% confidence level and 80% power, the estimates were found to be 422, 354 and 178 patients, 4 5 6 respectively. To increase the precision of the estimates of the different outcomes of the study, all 7 8 of the cohort of 450 breast and 250 cervical cancer cases will be considered in the analysis of each 9 10 of the specific objectives. 11 12 13 14 Data collection tools and techniques 15 16 Three data collectionFor tools will peer be used toreview address the objectives only of the project: an interviewer 17 18 19 administered questionnaire (Supplemental File), an in-depth interview guide, and a medical record 20 21 data extraction tool. The tools are being developed in English, translated into Amharic, and back 22 23 translated into English. The Amharic version will be used for conducting the interview. 24 25 26 27 The interviewer administered questionnaire is organized into two parts. The first part of the 28 29 questionnaire addresses participants’ socio-demographic characteristics, medical history, and 30 31 pathway to diagnosis which is adapted from a questionnaire for a similar study in Rwanda.[40] In 32 http://bmjopen.bmj.com/ 33 34 addition, this first phase of questionnaire also includes questions about patient reported outcomes 35 36 (levels of fatigue, pain, sleep disorder and depression). Depression was assessed using a validated 37 38 Patient Health Questionnaire-9 (PHQ-9).[41]. While the questions for fatigue, pain and sleeping 39

40 on September 25, 2021 by guest. Protected copyright. disorder were adopted from National Cancer Institute.[42, 43] This questionnaire will be 41 42 43 administered face to face by trained interviewers at the time of participants’ recruitment. 44 45 46 The second tool which will be administered at about one year after the diagnosis of the cases 47 48 investigates receipt of and adherence to treatments, financial hardship, and survivorship care 49 50 51 (Supplemental File). The questions are adapted from different standardized tools developed by the 52 53 National Cancer Institute,[42, 43] the Agency for Healthcare Research and Quality, the Centers 54 55 for Disease Control and Prevention of the U.S. Department of Health and Human Services.[44] To 56 57 58 8 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 improve the validity of the questions, the adapted questionnaire was reviewed by local and 4 5 6 international experts on the research subject and cancer care. Further, a pretest was performed to 7 8 enhance the clarity of the tool. Patients will be interviewed about one year after their cancer 9 10 diagnosis by a trained interviewer, in person when possible and by telephone otherwise. Phone 11 12 calls will be made at least three times at different times of the day, evening and weekends to 13 14 15 increase the response rate of the study participants. Those patients who are not interviewed through 16 For peer review only 17 this mechanism, will be considered as lost to follow-up.[45] For patients who died or are too ill to 18 19 be interviewed, a surrogate (relative or household member) familiar with their cancer care will be 20 21 22 interviewed. 23 24 25 The medical record data extraction tool will be used to collect information about date of diagnosis, 26 27 tumor characteristics (e.g., stage at diagnosis, metastasis and recurrence), initiation and completion 28 29 30 of treatments, and vital status from the medical charts of the patients. Medical record review will 31

32 occur at about one and two years after diagnosis. http://bmjopen.bmj.com/ 33 34 35 In addition to the interviewer-administered questionnaire and extraction tool, a semi-structured 36 37 interview guide will be developed and used for in-depth interviews. This instrument will include 38 39

40 patients’ knowledge and perception of breast and cervical cancer, and the patients’ experience on September 25, 2021 by guest. Protected copyright. 41 42 from the recognition of first symptom of the disease to diagnosis and treatment. Interviews will be 43 44 conducted in local language (Amharic). The principal investigator and two trained data collectors 45 46 47 who have experience in collecting qualitative data will conduct the in-depth interviews. Interview 48 49 guide and tape recorder will be used. The interviewers will use probing and question-rephrasing 50 51 techniques to clarify questions and obtain details from the respondents. The number of interviews 52 53 54 will be determined based on information saturation. 55 56 57 58 9 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Term definitions and measurements 4 5 6 Independent variables: Demographic variables (age at diagnosis, marital status, and age at first 7 8 9 child birth), socioeconomic variables (level of education, occupation, monthly family income, and 10 11 source of medical expenses), method of initial detection, time of first symptom/sign detection, 12 13 participant’s appraisal of first symptom/sign, participants immediate action to the first symptom, 14 15 triggers to seek medical care, health facility of the first medical consultation, number of healthcare 16 For peer review only 17 18 facilities visited before diagnosis, number of visits to healthcare facility before diagnosis, clinical 19 20 presentation at time of diagnosis, time of medical care sought, family history of breast/cervical 21 22 cancer, self-reported co-morbidities and traditional medicine use will be obtained through in 23 24 25 person face to face interview. 26 27 28 The existing literature lacks consistency in the definition of the time intervals for cancer diagnosis 29 30 and treatment delays, and traditionally has been classified as “patient delay” and “system 31 32 delay”.[46] For consistency, the Aarhus statement[47] recommended classifying these as “patient http://bmjopen.bmj.com/ 33 34 35 interval”, “diagnostic interval”, “treatment interval” and “total interval”. Our study is based on this 36 37 framework. Patient interval is defined as the interval from the date of first recognition of symptoms 38 39 (the time point when first bodily changes and/or symptoms are noticed) to the date of first clinical 40 on September 25, 2021 by guest. Protected copyright. 41 42 presentation (the date at which the patient first presented to a healthcare provider after first 43 44 recognition of symptoms).[47] Waiting for > 3 months before consulting a health care provider 45 46 will be considered to be a long patient interval.[48-50] 47 48 49 We will consider using local events to help patients recall the date of first symptom recognition 50 51 52 and presentation. If the participants are unable to recall the exact date of first symptom recognized 53 54 or date of first medical consultation made, they will be asked to provide a month, or year (was it 55 56 57 58 10 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 at the beginning, middle, or end of the year). If they remembered the month, the date will be 4 5 th 6 estimated as the 15 of that month; if the participants only said the beginning, middle or end of 7 8 the year, the estimated date will be 15th of February, June or October of the year, respectively. 9 10 While for those who are only able to provide the year, the estimated date will be June 30th of that 11 12 year.[40] 13 14 15 16 Diagnostic interval Foris defined peer as the interval review from the date of onlyfirst clinical presentation to the date 17 18 of pathologic diagnosis (the date at which the first histological or cytological confirmation of this 19 20 malignancy was reported). Treatment interval will be computed by subtracting the date of 21 22 23 confirmation from the date of treatment initiation. Total interval will be computed by subtracting 24 25 the date of first time recognition of symptom from the date of treatment initiation.[47] The date of 26 27 diagnosis and treatment initiation will be taken from the medical chart of the patients. 28 29 30 31 Stage at diagnosis will be grouped into early stage (patient presented with clinical stage II and

32 http://bmjopen.bmj.com/ 33 below) and advanced stage (patients presented with clinical stage III or above) diseases.[51, 52] 34 35 36 Data quality assurance mechanism 37 38 39 Several measures will be taken to maintain the quality of the research starting from designing the

40 on September 25, 2021 by guest. Protected copyright. 41 tool to data analysis and interpretations of the findings. Tool translation and back translation will 42 43 44 be done to ensure the consistency of the survey tools. In addition to this, the questionnaire will be 45 46 pre-tested and relevant corrections will be made. 47 48 49 Data collectors and supervisor will be recruited based on the level of education, ability to 50 51 communicate using the working language, and experience on data collection. Moreover, they will 52 53 54 be trained on the objectives of the study, data collection tools, interviewing techniques, and ethical 55 56 procedures before the implementation of the project. 57 58 11 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 12 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 In addition to the training of the data collectors, they will be supervised by the supervisor and 4 5 6 principal investigators. Filled questionnaires will be checked for their completeness and 7 8 consistency on daily bases by the supervisor. Biweekly meetings will be held with the supervisor 9 10 of the data collectors and the investigators to discuss and solve any problems encountered in the 11 12 data collection process. 13 14 15 16 To minimize errorsFor during datapeer entry, templates review will be developed only using Epi-Info using check 17 18 codes. After the entry is completed, the sample of the questionnaires will be rechecked for 19 20 correctness against the raw data, and necessary corrections will be made before the analysis. 21 22 23 24 To maintain the trustworthiness of the qualitative data, interviews will be collected, transcribed 25 26 and analyzed by individuals experienced in qualitative data collection and analysis. All interviews 27 28 will be tape recorded to grasp all the points during the interview. Moreover, data will be transcribed 29 30 by the data collectors on a daily bases to maintain the consistency and context of the discussion, 31

32 http://bmjopen.bmj.com/ 33 and checked for errors by listening back to the audio-recording and reading the transcripts 34 35 simultaneously. Finally, the transcribed data will be coded using NVivo software to facilitate the 36 37 reduction of the qualitative data without missing the central idea. 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 Data management and analysis plan 42 43 Qualitative data analysis 44 45 46 Specific objective 1: 47 For the qualitative data, audio data will be transcribed verbatim into 48 49 Microsoft Word files and translated from the local language to English. Before the analysis, the 50 51 text will be read through several times to obtain a sense of the whole and familiarize with the 52 53 data. Then word transcript of the data will be imported into NVivo software version 11[53] and 54 55 56 coded line by line. The codes will be compared based on differences and similarities and sorted 57 58 12 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 13 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 into categories, and categories will be grouped in themes. Finally, the result will be presented in 4 5 6 themes. 7 8 9 Quantitative data entry, cleaning and management 10 11 12 Deidentified data will be entered to the pre-designed template with appropriately programed 13 14 skipping patterns using Epi-Info 3.5.1 version. Cleaned data will be exported to Stata 14 software 15 16 to calculate summaryFor descriptive peer statistics, review including mean only (standard deviation) and median 17 18 19 (interquartile range) for continuous variable and proportions for categorical variables. Estimates 20 21 of population parameters will be presented with their 95% Confidence Interval. Statistical 22 23 significance will be declared at P value < 0.05. Follows analytical methods for each of the specific 24 25 26 objectives: 27 28 29 Specific objective 2 (to determine the duration of patient, diagnostic and treatment initiation 30 31 intervals) a descriptive analysis will be used. We will present means with their standard deviation

32 http://bmjopen.bmj.com/ 33 (SD) for those with normal distribution, and median and interquartile range (IQR) for those 34 35 36 variables with skewed distributions. In addition, we will calculate proportions with their 95%CI 37 38 for patients who waited > 3 months before seeking medical care and for those patients who 39 40 waited more than a month before receipt of diagnosis confirmation following date of on September 25, 2021 by guest. Protected copyright. 41 42 43 presentation. 44 45 46 Specific objective 3 and 4: To determine factors associated with patient and diagnostic intervals, 47 48 and the association between patient/diagnostic intervals and stage at diagnosis, we first run 49 50 bivariate analyses to select candidate explanatory variables. Variables reported as having an impact 51 52 53 on longer interval, and survival in the literature, and those variables P<0.25 with the dependent 54 55 variable in the bivariate analysis will be entered into the multivariable logistic regression model to 56 57 58 13 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 identify their independent effects. Before fitting the binary logistic regression model multi- 4 5 6 collinearity among the independent variables, outliers, and model fitness will be checked. Odds 7 8 Ratio with its 95% confidence interval will be calculated for each independent variable against the 9 10 dependent variable. 11 12 13 Specific objective 5 (to determine patient reported outcomes). Prevalence of cancer caused pain, 14 15 16 fatigue, and sleepingFor disorder peer will be computed. review Depression only will be measured by 9 items. Each 17 18 item is rated on a 3-point scale, giving maximum scores of 27. The total depression score will be 19 20 determined, and variation of depression scores at two time points (during diagnosis or treatment 21 22 23 and after treatment) will be assessed using repeated measures analysis. Then we will test for the 24 25 presence of statistical difference of the score across different participants’ characteristics, and 26 27 receipt of treatment. 28 29 30 Specific objective 6 and 7 (to describe treatment patterns, adherence and survivorship care): 31

32 http://bmjopen.bmj.com/ 33 descriptive statistics will be used to characterize the treatment pattern received by the patients 34 35 and level of adherence. We will compute the proportion (with 95% CI) of patients who received 36 37 radiotherapy, chemotherapy, hormonal therapy and survivorship care. In addition, multivariable 38 39 logistic regression analysis will be conducted to examine the association between participants 40 on September 25, 2021 by guest. Protected copyright. 41 42 characteristics and three separate outcomes: (1) receipt of radiotherapy and chemotherapy; (2) 43 44 adherence to chemotherapy and hormonal therapy; and (3) receipt of survivorship care. Variables 45 46 with P value < 0.25 on bivariate analysis will be retained in the final multivariable logistic 47 48 49 regression. 50 51 52 Specific objective 8 (to estimate the financial burden of breast and cervical cancer on patients 53 54 and their families): data will be analyzed descriptively and both the direct and indirect patient 55 56 57 58 14 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 related costs will be computed. The mean or median cost of illness will be computed. Financial 4 5 6 difficulties and coping mechanisms made by the patients will be described. 7 8 9 Specific objective 9 (to compute the two-year survival rates and the determinants of survival): 10 11 Survival will be estimated using the Kaplan-Meier method and compared using the log-rank test. 12 13 The time to event for the following three types of survival rates will be computed as follow [54]: 14 15 16 For peer review only 17  Disease Free Survival (DFS) will be computed for stage I-III cases treated with curative 18 19 intention from the date of primary treatment to the date of local, contra-lateral or distant 20 21 recurrence or death from breast or cervical cancer. 22 23 24  Distant DFS will be computed from the date of primary treatment to the date of distant 25 26 metastasis or death from breast or cervical cancer. 27 28  Overall Survival (OS) will be computed from the date of diagnosis to the date of death. 29 30 31  For patients who remained alive and disease-free, data will be censored at the date of the

32 http://bmjopen.bmj.com/ 33 last contact. 34 35 We will also compute hazard ratio (HR) for time to event outcomes, with its corresponding 95% 36 37 38 CIs, and associated p-values. Cox’s proportional hazard model will be used to identify factors 39

40 associated with the survival of the patients. Overall survival will be estimated using the Kaplan- on September 25, 2021 by guest. Protected copyright. 41 42 Meier method and compared using the log-rank test. The proportional hazards assumption will be 43 44 45 checked using graphical method and goodness of fit test. Multivariable Cox regression analysis 46 47 will be used to estimate the hazard of all-cause HR associated with the pre-selected various 48 49 prognostic factors that we are studying. 50 51 52 53 54 55 56 57 58 15 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Patient and public involvement 4 5 6 Neither patients nor the public were involved in the design of the study, the types of research 7 8 9 questions and study outcomes, or recruitment of participants. However, we conducted a rapid 10 11 ethical assessment among women with breast and cervical cancer, family members, and health 12 13 care providers for designing consent of study participants. We plan to disseminate the results of 14 15 this research to study participants, staff of healthcare facilities where the study participants are 16 For peer review only 17 18 recruited, Addis Ababa Health Bureau, Federal Ministry of Health, cancer control advocates, 19 20 media, and researchers through preparation of fact sheets for lay audience, publications in 21 22 international peer-reviewed journals, and presentations in conferences. 23 24 25 26 Ethical considerations and result dissemination 27 28 29 Ethical clearance has been secured from the Institutional Review Board (018/17/SPH) of Addis 30 31 Ababa University, College of Health Science. Prior to the start of study subjects’ recruitment, we

32 http://bmjopen.bmj.com/ 33 conducted rapid ethical assessment to design our consent process.[55] Based on this assessment, 34 35 we found that most of the participants were not comfortable to written consent for different reasons. 36 37 38 Accordingly, we decided to use verbal consent, which has been approved by the IRB of College 39

40 of Health Science of Addis Ababa University. Eligible patients will be verbally informed, by on September 25, 2021 by guest. Protected copyright. 41 42 trained research personnel, regarding the nature and purpose of the study, and given time to decide 43 44 45 whether or not to participate in the follow-up study. Enrollment will be fully based on the voluntary 46 47 participation of the study participants and respondents who are interested to avoid specific 48 49 questions or discontinue the interview will be allowed to do so. In the event family members are 50 51 52 grieving when contacted for vital status, we will offer our condolences and ask then them if they 53 54 will be willing to speak with us at a later time. 55 56 57 58 16 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Confidentiality of any information related to the patient and her clinical history will be maintained 4 5 6 by keeping both the hard copy and softcopy of every collected data in a locked cabinet and 7 8 password secured computer. Only the principal investigators will have access to the deidentified 9 10 data that will be kept in a secure place. All data will be coded without personal identifiers. All 11 12 analyses will be on deidentified and coded data. 13 14 15 We intend to present the results of our follow-up study via scientific publications in peer-reviewed 16 For peer review only 17 journals as well as through presentation to stakeholders including the public, patients, clinicians 18 19 and policymakers. 20 21 22 23 Information gathered from this study will inform clinical guidelines and public health policies 24 25 improve the quality of cancer patients’ care delivered in the city, as well as other parts of the 26 27 country. It will also be used to produce fact-based materials to develop "stories" that illustrate the 28 29 30 compelling need for increased resources to reduce suffering and death from cancer. Experience of 31

32 the survivors will become available and presented to the public to enrich awareness campaigns http://bmjopen.bmj.com/ 33 34 and show that cancer is not a death sentence[56] but patients can as well be cured. Furthermore, 35 36 this collaborative project will provide research collaboration opportunities for several graduate 37 38 39 students, residents, and junior and senior faculty members of Addis Ababa University and in doing

40 on September 25, 2021 by guest. Protected copyright. 41 so will enhance the capacity of the university in conducting cancer care delivery and epidemiologic 42 43 research. 44 45 46 47 Supplemental Files 48 49 50 Supplemental file 1: Questionnaire 51 52 53 54 55 56 57 58 17 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4 Acknowledgements 5 6 7 The authors would like to thank the study participants, data collectors, and supervisors. 8 9 10 11 Authors’ contributions 12 13 14 AG, AA, AWY, MA, and AJ conceptualize the study. AG wrote the first draft of the manuscript. 15 16 AA, AWY, SH, MA,For EJK, LEP, peer and AJ commented review on the designingonly the study and reviewed the 17 18 19 final draft of the manuscript. All authors read and approved the final draft of the manuscript. 20 21 Funding 22 23 24 This project is supported by the Intramural Research Department of the American Cancer 25 26 Society. The funder has no role in the study design; in the collection, analysis and interpretation 27 28 of the data; in the writing of the report; and in the decision to submit the paper for publication. 29 30 31 Competing interests

32 http://bmjopen.bmj.com/ 33 The authors declare that they have no competing interests. 34 35 36 REFERENCES 37 38 1. Torre LA, Islami F, Siegel RL, et al. Global Cancer in Women: Burden and Trends. Cancer 39 Epidemiol Biomarkers Prev 2017;26(4):444-57 40 on September 25, 2021 by guest. Protected copyright. 41 2. Kantelhardt EJ, Gizaw M, Getachew S, et al. A Review on Breast Cancer Care in Africa. Breast Care 42 43 2015;10:364-70. 44 3. Jemal A, Bray F, Forman D, et al. Cancer Burden in Africa and opportunities for prevention. Cancer. 45 46 2012;118:4372-84. 47 4. Timotewos G, Solomon A, Mathewos A, et al. First data from a population based cancer registry in 48 49 Ethiopia. Cancer epidemiology 2018;53:93-8. PubMed PMID: 29414637. Epub 2018/02/08. eng. 50 51 5. Kantelhardt EJ, Moelle U, Begoihn M, et al. Cervical cancer in Ethiopia: Survival of 1,059 patients 52 who received oncologic therapy. The Oncologist 2014;19:727-34. 53 54 6. Kantelhardt E.J, Zerche P, Mathewos A, et al. Breast cancer survival in Ethiopia: A cohort study of 55 1,070 women. Int J Cancer 2013;135:702–9. 56 57 58 18 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 7. World Health Organization. Global status report on noncommunicable diseases 2010. Geneva, 4 5 Switzerland: 2011.accessed on october 15, 2018 from 6 https://www.who.int/nmh/publications/ncd_report2010/en/ 7 8 8. Dye TD, Bogale S, Hobden C, et al. Experience of initial symptoms of breast cancer and triggers for 9 10 action in Ethiopia. Hindawi Publishing Corporation, International Journal of Breast Cancer 11 2012;2012:1-5. 12 13 9. Dye TDV, Bogale S, Hobden C, et al. A mixed-method assessment of beliefs and practice around 14 breast cancer in Ethiopia: Implications for public health programming and cancer control. Global 15 16 Public Health, AnFor International peer Journal for review Research, Policy andonly Practice 2011;6:719-31. 17 10. Montazeri A. Quality of life data as prognostic indicators of survival in cancer patients: an overview 18 19 of the literature from 1982 to 2008. Health and Quality of Life Outcomes 2009;7:1-21 20 21 11. Montazeri A. Health-related quality of life in breast cancer patients: A bibliographic review of the 22 literature from 1974 to 2007. Journal of Experimental & Clinical Cancer Research 2008;27:1-31 23 24 12. The Federal Democratic Republic of Ethiopia Ministry of Health. Health Sector Transformation Plan 25 2015/16 - 2019/20. 2015. Accessed on Dec. 2018, from file:///C:/Users/user/Downloads/ethiopia- 26 27 health-system-transformation-plan.pdf 28 13. Lemlem SB, Sinishaw W, Hailu M, et al. Assessment of knowledge of breast cancer and screening 29 30 methods among nurses in university hospitals in Addis Ababa, Ethiopia, 2011. Hindawi Publishing 31

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32 37. Ethiopia Federal Ministry of Health. Ethiopia’s Household Health Services Utilization and http://bmjopen.bmj.com/ 33 Expenditure Survey Briefing Notes. Addis Ababa, Ethiopia. 2014:5 accessed from 34 35 https://www.hfgproject.org/wp-content/uploads/2014/04/Ethiopia-NHA-Survey-Briefing-Notes.pdf 36 38. African Cancer Regisrty Network. Addis Ababa population Based cancer registery. Addis Ababa City 37 38 Cancer Registry - African Cancer Registry Network accessed on June 27, 2017 from 39

40 http://afcrn.org/membership/members/100-Addisababa. on September 25, 2021 by guest. Protected copyright. 41 39. Harirchi I, Karbakhsh M, Hadi F, et al. Patient delay, diagnosis delay and treatment delay for breast 42 43 cancer: Comparison of the pattern between patients in public and private health sectors. Arch Breast 44 Cancer 2015;2:15-20 45 46 40. Pace LE, Mpunga T, Hategekimana V, et al. Delays in Breast Cancer PresentationandDiagnosis at 47 48 TwoRural Cancer Referral Centers in Rwanda. The Oncologist 2015;20:780-8. 49 41. Hanlon C, Medhin G, Selamu M, et al. Validity of brief screening questionnaires to detect depression 50 51 in primary care in Ethiopia. Journal of affective disorders 2015;186:32-9. PubMed PMID: 26226431. 52 Epub 2015/08/01. eng. 53 54 42. National Cancer Instutite and Northern California. Assessment of Patients’ Experience of Cancer 55 Care (APECC) Study. Accessed from 56 https://healthcaredelivery.cancer.gov/apecc/ 57 58 21 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 22 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 43. National Cancer Instutite U.S. Department of Health and Human Services National Institutes of 4 5 Health. Adolecent and Young Adult Health Outcome and Patient Experiance. Follow-up survey. 6 44. The Agency for Healthcare Research and Quality and The Centers for Disease Control and 7 8 Prevention of the U.S. Department of Health and Human Services. Medical Expenditure Survey. 9 10 Your Experiences with Cancer. Accessed from https://healthcaredelivery.cancer.gov/meps/ 11 45. Harlan LC, Lynch CF, Keegan THM, et al. Recruitment and follow-up of adolescent and young adult 12 13 cancer survivors: the AYA HOPE Study. J Cancer Surviv 2011;5:305-14. 14 46. Freitas AG, Weller M. Patient delays and system delays in breast cancer treatment in developed and 15 16 developing countries.For Cien Saudepeer Colet 2015;20:3177-89. review PubMed only PMID: 26465859. Epub 17 2015/10/16. eng. 18 19 47. Weller D, Vedsted P, Rubin G, et al. The Aarhus statement: improving design and reporting of 20 21 studies on early cancer diagnosis. Br J Cancer 2012;106:1262-7. PubMed PMID: 22415239. Pubmed 22 Central PMCID: 3314787. Epub 2012/03/15. eng. 23 24 48. Sharma K, Costas A, Damuse R, et al. The Haiti Breast Cancer Initiative: Initial Findings and 25 Analysis of Barriers-to-Care Delaying Patient Presentation. Hindawi Publishing Corporation: Journal 26 27 of Oncology 2013;2013:1-6 28 49. Ramirez AJ, Westcombe AM, Burgess CC, et al. Factors predicting delayed presentation of 29 30 symptomatic breast cancer: a systematic review. Lancet 1999;353:1127-31. 31

32 50. Sharma K, Costas A, Shulman LN, et al. A Systematic review of barriers to breast cancer care in http://bmjopen.bmj.com/ 33 developing countries resulting in delayed patient presentation. Hindawi Publishing Corporation 34 35 Journal of Oncology 2012;2012:1-8 36 51. Edge SB. AJCC cancer staging manual. 7th ed. . New York: Springer; 2010. Accessed on January 37 38 2018 from https://cancerstaging.org/references- 39 tools/deskreferences/Documents/AJCC%207th%20Ed%20Cancer%20Staging%20Manual.pdf 40 on September 25, 2021 by guest. Protected copyright. 41 52. Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol 42 43 Obstet 2009;105:107-8. PubMed PMID: 19342051. Epub 2009/04/04. eng. 44 53. Hamunyela RH, Serafin AM, Akudugu JM. Strong synergism between small molecule inhibitors of 45 46 HER2, PI3K, mTOR and Bcl-2 in human breast cancer cells. Toxicology in vitro : an international 47 journal published in association with BIBRA 2017;38:117-23. PubMed PMID: 27737796. Epub 48 49 2016/10/21. eng. 50 51 54. Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end 52 points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 2007;25:2127-32. PubMed 53 54 PMID: 17513820. Epub 2007/05/22. eng. 55 56 57 58 22 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 23 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 55. Gebremariam A, Yalew AW, Hirpa S, et al. Application of the rapid ethical assessment approach to 4 5 enhance the ethical conduct of longitudinal population based female cancer research in an urban 6 setting in Ethiopia. BMC Medical Ethics 2018;19:1-12. 7 8 56. Azubuike SO, Muirhead C, Hayes L, et al. Rising global burden of breast cancer: the case of sub- 9 10 Saharan Africa (with emphasis on Nigeria) and implications for regional development: a review. 11 World Journal of Surgical Oncology 2018;16:1-13. 12 13 14 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 23 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 24 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4 Annexes 5 6 Annexe I Breast Cancer Survey English Version Questionnaire 7

8 Questionner ID. ______9

10 Patient’s Medical Record Number ______11

12 Name of the Health facility______13 14 PART I Informed Consent Form for Breast Cancer Participants 15 16 Information Sheet For peer review only 17 Introduction: Thank you so much. My name is ______. I am doing on behalf of 18 19 Addis Ababa University and American cancer society for the project entitled breast and cervical cancer 20 21 patients’ journey. 22 Question: Please can you tell me why you come to this health facility? 23 24 ______25 ______26 27 This is a research project on newly diagnosed breast cancer patients in Addis Ababa. Breast cancer is one 28 29 of the leading causes of morbidity and mortality among Ethiopian women. We are going to give you 30 information about the research project and invite you to be part of it. You may take some time to decide on 31

32 whether or not you will participate in the research. Before you decide, you can talk to anyone you feel http://bmjopen.bmj.com/ 33 comfortable with about the research 34 35 36 Purpose of the research: Although Breast cancer can be detected early and treated, most breast cancer 37 38 patients in Addis Ababa and Ethiopia present very late, after the disease spread to other parts of the body. 39 However, very little is known about the causes of their delay. Also unknown are their pathways to treatment 40 on September 25, 2021 by guest. Protected copyright. 41 and psychosocial wellbeing, and the financial burden of the disease on them and their families. In this study, 42 we are planning to assess the health seeking behavior, treatment pathways; patient reported outcomes, 43 44 financial burden and survival of newly diagnosed breast cancer patients in Addis Ababa. 45 46 47 Participation: We are asking you and others to voluntarily participate in this study because you have been 48 recently diagnosed with breast cancer. Over the next two years, we will have additional questionnaire to 49 50 learn about your experience related to your disease. Our study is completely interview based and does not 51 involves any invasive procedure. 52 53 54 Confidentiality: Any information that we collect about you during this research will be kept confidential. 55 Information about your identity will be put away after re-coding your file, and kept in a secured place. Only 56 57 58 1 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 25 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 the principal investigators will be able to link your identity with the code number, should this become 4 5 necessary to assist you medically. However, all the clinical information, which is devoid of your identity, 6 may be seen by the researchers; and if need be by ethics committees. 7 8 9 Benefits: You will receive only transport allowance as a compensation for the time you will spend for 10 11 interview. Your participation is very important for us to find the answer to the research question which in 12 turn benefits the society especially women and their families. 13 14 15 Risks: The study has no risk for the participants and interviews will be conducted in privacy, dedicated 16 office for the study. For peer review only 17 18 19 Inducement, incentive and Compensation: This study process has no any form of inducement, coercion 20 and the study does not bring any risks that incur compensation. 21 22 23 Results Dissemination: The researcher is responsible for dissemination of findings in different seminars 24 25 and conferences. Moreover, maximum effort will be done to publish the finding in scientific reputable 26 journal. 27 28 29 Right to Refuse or Withdraw: You do not have to take part in this research if you do not wish to do so 30 and refusing to participate will not affect your treatment at this hospital or clinic in any way. You will still 31

32 have all the benefits that you would otherwise have at this clinic or hospital. You may stop participating in http://bmjopen.bmj.com/ 33 34 the research at any time that you wish without losing any of your rights as a patient here. Your treatment at 35 this clinic will not be affected in any way. 36 37 38 Person to Contact: You have the right to ask information that is not clear about the research context and 39 content before and or during the research work. If you have any questions, you may ask or contact to the 40 on September 25, 2021 by guest. Protected copyright. 41 persons stated below. You can contact them any time, even after the study has started. If you wish to ask 42 questions later, you may contact the investigator at the following address; 43 44 If you have any further question and in case of urgency you can contact 45 46 Dr. Adamu Addissie (0115547319; E-mail [email protected]) 47 Dr. Mathewos Assefa (E-mail [email protected]) 48 49 Mr. Alem G.mariam (E-mail [email protected]) 50 51 Institutional Review Board 52 53 Address Addis Ababa University, College of Health Sciences 54 Telephone +251-115538734 55 56 57 58 2 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 26 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Part II. Consent form 4 I, the undersigned, confirm that, as I give consent to participate in the study, it is with a clear 5 6 understanding of the objectives and conditions of the study and with recognition of my right to withdraw 7 from the study if I change my mind. 8 9 I ______do herby give consent to Mr. /Mrs./Miss 10 11 ______to include me in the proposed research. I have been given the 12 necessary information about the research. I have also been assured that I can withdraw my consent at any 13 14 time without penalty or loss of benefits. The proposal has been explained to me in the language I 15 understand. 16 For peer review only 17 Are you willing to participate in the study? 18 Yes No (Terminate the interview and say 19 20 thank you) 21 22 Patients contact Address (mobile) 23 Participants Mobile No. ______24 25 Family/partner Mobile No. ______26 27 Name of interviewer Dr/ Mr. /Mrs./Miss ______Date _____/_____ / _____ 28 29 30 Supervisor 31 Dr/ Mr. /Mrs./Miss ______signature ______Date ___ / ___ /____ 32 http://bmjopen.bmj.com/ 33 BREAST CANCER PATIENT SURVEY - I 34 Questionner ID. ______35 36 Date of interview: _____/_____/______37 38 Patient’s Medical Record Number 39 ______40 Pathology Number: ______Facility Pathology performed: ______on September 25, 2021 by guest. Protected copyright. 41 42 Date of pathology result reported: ___/______/ ______43 44 45 Name of the Health facility______Department: ______46 47 Participant Address 48 49 Sub-city: ______District: ______House No. ______50 51 Participant’s phone number: ______52 53 Identification of proxy 54 55 56 57 58 3 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 27 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 1. If you had to choose, which person would you say knows best how you are doing since your cancer 4 5 diagnosis? So that we may contact them in the future, may I have their phone number? 6 I. ______phone number______R/nship ______7 8 II. ______phone number______R/nship ______9 10 III. ______phone number______R/nship ______11 2. In the future if we are unable to reach you, may we have your permission to speak with any of these 12 13 persons to find out how you are doing? 14 0- No 15 16 1- Yes For peer review only 17 1. Socio-demographic characteristics of participant 18 19 20 Q.No. Questions Choices Remarks 21 101. How old are you? (age in years) Enter ______22 23 102. What is your ethnicity? ______24 25 103. What is your religion? 1. Christians 26 2. Islam 27 88. Others, specify ______28 104. Participants highest level of 1. Can’t read and write 29 education obtained 2. Can read and write 30 3. Elementary (Grade, 1-8th) 31 4. Secondary (Grade, 9-12th) 32 5. Diploma http://bmjopen.bmj.com/ 33 6. Bachelor’s Degree 34 7. Masters and above 35 36 105. Participant’s occupation 1. Housewife 37 2. Government employee 38 3. Private employee 39 4. Merchant

40 5. Daily laborer on September 25, 2021 by guest. Protected copyright. 41 6. Student 42 7. Retired 43 88. Other (specify)______44 45 106. What is your current marital status? 1. Married 46 2. Single 47 3. Divorced Q109 48 4. Separated 49 88. Others, specify______50 107. Partner’s educational level 1. Can’t read and write 51 2. Can read and write 52 3. Elementary (Grade, 1-8th) 53 4. Secondary (Grade, 9-12th) 54 5. Diploma 55 6. Bachelor’s Degree 56 57 58 4 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 28 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 7. Masters and above 4 5 108. Partner’s occupation? 1. Government employee 6 2. Private employee 7 3. Daily laborer 8 4. Merchant 9 5. Student 10 6. Has no job 11 7. Pensioned 12 88. Other (specify)______13 109. Number of individuals that live in ______(number) 14 your house hold including yourself 15 16 110. Including incomeFor provided peer by you, review1. 600 birr and onlyabove 17 your spouse and others you regard 2. 601 - 1,650 birr 18 as a family who live in your 3. 1,651 - 3,200 birr 19 household, what was your total 4. 3,201 - 5,250 birr 20 average monthly household income 5. 5,251 - 7,800 birr 21 (from all sources) 6. 7,801 - 10,900 birr 22 7. More than 10,900 birr 23 24 111. How do you pay your medical care 1. Out of pocket go to 25 expenses? 2. Free medical care Q113 26 3. Government insurance 27 4. Private insurance 28 5. Employing organization 29 112. What percent of your medical 30 expense is covered by the 31 insurance? ______%

32 http://bmjopen.bmj.com/ 33 113. Have you ever give birth? 0- No Q. 201 34 1- Yes 35 114. How many children do you have? ______(number) 36 37 115. How old were you when you had ______years 38 your first child? 39 40 2. Participants’ lifestyle and medical condition on September 25, 2021 by guest. Protected copyright. 41 42 Q. N Questions Choices Remark 43 201. Do you have any medically confirmed 0. No Q. 203 44 chronic medical conditions? 1. Yes 45 202. Which of medical conditions do you No Yes 46 have? (multiple Reponses possible) 1. Diabetes 0 1 47 2. Hypertension 0 1 48 Read each of listed diseases 3. Heart disease 0 1 49 50 4. Tuberculosis 0 1 51 5. Kidney disease 0 1 52 88. Others specify ______53 A. ______54 B. ______55 C. ______56 57 58 5 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 29 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 203. Have any of your relatives ever been 0. No Q. 205 4 diagnosed with breast cancer? 1. Yes 5 99. Refused 6 100. I do not know 7 8 204. If yes, relationship with the patient? 1. Mother 9 Check all that apply 2. Sister 10 88. Others, specify______11 12 205. Have you ever smoked cigarettes? 0. No Q. 209 13 1. Yes 14 15 206. For how long do you ever smoked? ______months/years 16 207. Do you smokeFor cigarettes peer regularly now? review 0. No only Q. 209 17 1. Yes 18 208. On average, how many cigarettes do you ______# cigarettes per day 19 (1pack = 20 cigarettes) 20 smoke per day? 21 99. Refused 22 100. Don’t know 23 209. In the year before your diagnosis with 0. No Q. 212 24 CANCER, have you ever drunk any type 1. Yes 25 of alcoholic beverage? 26 27 210. Do you have habit of drinking alcohol 0. No Q. 212 28 currently 1. Yes 29 99. Refused 30 211. On average, how many drinks do you ______bottle 31 have per day? 99. refused 32 http://bmjopen.bmj.com/ 33 100. I do not know 34 212. Weight of the participant in KG ______kilograms 35 36 213. Height of the participants in cent meters ______Cent Meters 37 without shoes? 38 39

40 3. Pre-Diagnosis History of participants on September 25, 2021 by guest. Protected copyright. 41 42 Q. N Question Choices Remark 43 301. Have you ever heard of breast cancer 0. No Q. 303 44 prior to your first symptom 45 1. Yes 46 302. If so, how did you learn about breast 1. Mass media (TV, radio, internet) 47 cancer? (multiple answers are 2. Healthcare provider 48 possible) 3. Friend/family/neighbours 49 50 (Read the options) 88. Other specify: ______51 303. Do you know how to examine your 0. No 52 breasts using your hand for lumps? 1. Yes 53 304. Before you feel/saw the symptom/sign 0. No 54 of your breast problem, did you ever 55 1. Yes 56 57 58 6 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 30 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 examine your breast using your hand for 4 lumps? 5 6 7 305. Before you feel/saw the symptom/sign 0. No 8 of your breast problem, did a doctor or 1. Yes 9 nurse ever examine your breast for 10 lump? 11 306. Before you feel/saw the symptom/sign 0. No 12 of your breast problem, did you have a 1. Yes 13 mammogram (a machine to look for a 14 lump or other abnormality in your 15 breast)? 16 For peer review only 17 307. On what day did you first notice the ____/ _____/ ______dd/mm/yyyy 18 problem with your breast? (pleas identify any information that the 19 patient can provide, whether a full date, 20 21 a month and year, or the year only) 22 308. If you do not remember the month, but 1. Beginning 23 remember the year, was it the 2. Middle 24 beginning, middle, or end of the year? 3. End 25 26 4. Don’t know the year 27 309. What was the symptom you first 1. Breast pain 28 noticed? 2. Breast Mass 29 3. Nipple discharge 30 Multiple response is possible 31 Read the options 4. Skin changes 32 http://bmjopen.bmj.com/ 88.Other, specify: ______33 310. Were you pregnant when you first 0. No 34 developed this symptom? 35 1. Yes

36 311. Were you breastfeeding when you first 0. No 37 developed the symptom? 38 1. Yes

39 312. Who discovered the symptom? 1. Self 40 on September 25, 2021 by guest. Protected copyright. 41 2. Husband 42 3. Healthcare provider 43 88. Others, specify ______44 313. What was your immediate 1. Mich (sun stroke) 45 impression/suspicion to the first 2. Tumor 46 symptom? 47 3. Cancer 48 4. Nothing 49 88. other, specify ______50 314. What was your primary action to the 1. I did nothing 51 first symptom? 52 2. I went to health facility immediately 53 3. I went to traditional healers 54 4. I performed ritual activities 55 88. Others, specify ______56 57 58 7 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 31 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 315. Did you see a traditional healer first for 0. Yes 4 your symptom? 1. No Q317 5 6 99. Refused 7 316. If yes, can you describe it? ______8 ______

9 ______10 11 ______12 317. Were there any ritual activities that you 0. Yes 13 have done for your symptom as a 1. No 14 treatment? 99. Refused Q319 15 16 318. If yes, can youFor tell me whatpeer you did? review1. Holly water only 17 2. Praying 18 Multiple response possible 88. Others, specify 19 Read the options 20 21 319. When was the first time you visited a ____/_____/_____ dd/mm/yyyy 22 health facility for your cancer? 23 24 320. If you do not remember the month, but 1. Beginning 25 remember the year, was it the 2. Middle 26 beginning, middle, or end of the year? 27 3. End 28 4. Don’t know the year 29 321. Which level of health facility did you 1. Health center 30 first visited for your problem? 2. Public Hospital 31 3. Private hospital 32 4. Private clinic http://bmjopen.bmj.com/ 33 322. Did you experience additional 0. No Q. 324 34 symptoms before you went to healthcare 1. Yes 35 provider? 36 37 323. If yes, what were the additional 1. Pain 38 symptoms you experienced? 2. Lumps 39 3. Itching or burning

40 Multiple response possible 4. Nipple discharge on September 25, 2021 by guest. Protected copyright. 41 Read options 88. Other, Specify: ______42 43 324. What motivated (triggered) you to see a 1. First symptom 44 healthcare provider for your symptom? 2. Additional symptoms 45 3. Family member/Friend 46 4. A provider secondary to other care 47 88. Other, Specify______48 325. When was the time your breast problem ____/ ____/______(dd/mm/yyyy) 49 confirmed as cancer by biopsy? 50 51 Take the date from the pathology report 52 53 326. How many health facilities did you ______health facilities 54 visited before you received a final 55 diagnosis for your problem? 56 57 58 8 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 32 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 327. How many times did you go to a health ______times 4 facility before you received a final 5 diagnosis for your problem? 6 7 8 For women who delayed more than three months prior to seeking medical care at a health center or 9 hospital (if not go to part 4) 10 11 328. What was the single most ______12 important factor that prevented ______13 you from seeking medical care 14 sooner? 15 329. Did any of the following 1. I wasn’t bothered by the problem at first 16 For peer review only 17 prevent you from seeking 2. I was too busy at home or at my job 18 medical care at a health center 3. I was afraid of being examined by a doctor 19 or hospital sooner? or other health provider 20 Read the choices and circle all 4. I was afraid of examination results 21 that apply 22 5. I was afraid of the treatments, including 23 potentially losing my breast 24 6. I visited a traditional healer first 25 7. I didn’t know where an appropriate 26 medical facility was 27 28 8. I didn’t want anyone knowing I had a 29 breast problem 30 9. I thought treatment might be too expensive 31 88. Other, specify: 32 http://bmjopen.bmj.com/ 33 ______34 35 36 37 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 9 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 33 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4.Patients Reported Outcome 4 5 4.1. Participants’ experience of cancer related pain 6 7 The following questions ask about any physical pain you may experience from your cancer within the last 4 8 weeks. This includes pain from surgery for cancer, pain from cancer treatments (chemotherapy or radiation), 9 or pain from the disease itself. Please remember to answer these questions about cancer related pain only 10 11 12 S.N Question Response Remarks 13 14 1. Do you have any pain from your cancer 0. No If “No” skip to 4.2 15 and /or its treatment, even if it was 1. Yes 16 mild? For peer review only 17 2. If yes, what is the source of your pain? 1. Lesion in the cancer cite 18 2. The surgical procedure 19 3. Drug side effect 20 88. Other; specify______21 22 3. During the past 4 weeks, how would you 1. Very Severe 23 rate your severity of pain? 2. Severe 24 3. Moderate 25 4. Mild 26 27 4. Have you taken medicine (prescribed or 0. No If “No” skip to Q5 28 over the counter) to relieve your pain? 1. Yes 29 30 5. If yes, how often do you take the 1. less than once a week 31 medicine? 2. once a week

32 3. twice a week http://bmjopen.bmj.com/ 33 4. 3 or more times a week 34 35 6. How much did pain interfere with your 0. Not at all 36 normal work (both outside and in the 1. A little 37 home) 2. Quite a bit 38 39 3. Very much

40 7. Did you have any pain in your arm or 0. Not at all on September 25, 2021 by guest. Protected copyright. 41 shoulder? 1. A little 42 2. Quite a bit 43 44 3. Very much 45 8. Did you have a swollen arm or hand? 0. Not at all 46 1. A little 47 2. Quite a bit 48 3. Very much 49 50 9. Was it difficult to raise your arm or to 0. Not at all 51 move it sideways? 1. A little 52 2. Quite a bit 53 3. Very much 54 55 56 57 58 10 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 34 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 10. Have you had any pain in the area of your 0. Not at all 4 affected breast? 1. A little 5 6 2. Quite a bit 7 3. Very much 8 9 11. Was the area of your affected breast 0. Not at all 10 swollen? 1. A little 11 2. Quite a bit 12 13 3. Very much 14 15 12. Have you had skin problems on or in the 0. Not at all 16 area of your affectedFor breast peer (e.g., itchy, review 1. A little only 17 dry, flaky)? 2. Quite a bit 18 3. Very much 19 20 21 4.2. Participants Cancer related Fatigue 22 23 The following questions ask about any fatigue you may experience from your cancer within the last 4 24 25 weeks. This may be resulted from surgery for cancer, pain from cancer treatments (chemotherapy or 26 radiation), or the disease itself. Please remember to answer these questions about cancer related fatigue 27 only 28 29 S. N Question Response Remarks 30 31 1. Over the past 4 weeks, has there been at least a 2-week 0. No If No skip to

32 period when you had significant fatigue, a lack of energy, or 1. Yes 4.3 http://bmjopen.bmj.com/ 33 an increased need to rest every day or nearly every day 34 35 2. Do you feel weak all over or heavy all over? 0. No 36 1. Yes 37 3. Do you have trouble concentrating or paying attention 0. No 38 1. Yes 39 4. Do you have losing your interest or desire to do things you 0. No 40 usually do 1. Yes on September 25, 2021 by guest. Protected copyright. 41 42 5. Do you have trouble falling asleep, staying asleep, or 0. No 43 44 waking too early 1. Yes 45 46 6. Do you find yourself sleeping too much compared to what 0. No 47 you usually sleep 1. Yes 48 49 7. Have you found that you usually do not feel rested or 0. No 50 refreshed after you have slept 1. Yes 51 52 8. Do you have to struggle or push yourself to do anything 0. No 53 1. Yes 54 55 56 57 58 11 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 35 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 9. Did you find yourself feeling sad, frustrated, or irritable 0. No 4 because you felt fatigue? 1. Yes 5 6 7 10. Did you have difficult finishing something you had started 0. No 8 to do because of feeling fatigued? 1. Yes 9 10 11. Did you have trouble remembering things? For example, did 0. No 11 you have trouble remembering where your keys were or 1. Yes 12 what someone had told you a little while ago? 13 14 12. Did you find yourself feeling sick or unwell for several 0. No 15 hours after you had done something that took some effort? 1. Yes 16 For peer review only 17 18 13. Has fatigue made it hard for you to do your work, take care 0. No 19 of things at home, or get along with other people? 1. Yes 20 21 22 4.3. Depression 23 Over the past 2 weeks, how often have you been bothered by any of the following problems? 24 Instruction: Several days (2-6 days), more than half of the days (7-11days), nearly every day (12-14days) 25 26 S.N About your feeling (PROBLEMS WITH…) Response Remarks 27 1. Does your interest or pleasure in doing things was 0-No GO TO Q 2 28 decreased so much 1-Yes 29 How often do you felt over the last two weeks? 1-several days 30 2-Morethan half of the days 31 3-Nearly every day 32 http://bmjopen.bmj.com/ 33 2. Feeling down, depressed or hopeless 0-No GO TO Q 3.1 34 1-Yes 35 How often do you felt over the last two weeks? 1-several days 36 2-Morethan half of the days 37 3-Nearly every day 38 3.1 Trouble failing asleep or staying asleep 0-No GO TO Q 3.2 39 1-Yes 40 How often do you felt over the last two weeks? 1-several days on September 25, 2021 by guest. Protected copyright. 41 2-Morethan half of the days 42 3-Nearly every day 43 3.2 Trouble by a sleeping too much 0-No GO TO Q 4 44 45 1-Yes 46 How often do you felt over the last two weeks? 1-several days 47 2-Morethan half of the days 48 3-Nearly every day 49 4. Feeling tired or having little energy 0-No GO TO Q 5.1 50 1-Yes 51 How often do you felt over the last two weeks? 1-several days 52 2-Morethan half of the days 53 3-Nearly every day 54 5.1 Poor appetite 0-No GO TO Q 5.2 55 1-Yes 56 57 58 12 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 36 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 How often do you felt over the last two weeks? 1-several days 4 2-Morethan half of the days 5 3-Nearly every day 6 5.2 Overeating 0-No GO TO Q 6 7 1-Yes 8 9 How often do you felt over the last two weeks? 1-several days 10 2-Morethan half of the days 11 3-Nearly every day 12 6. Feeling bad about yourself-or that you are a failure or 0-No GO TO Q 7 13 have let yourself or your family down 1-Yes 14 How often do you felt over the last two weeks? 1-several days 15 2-Morethan half of the days 16 For peer review3 -onlyNearly every day 17 7. Trouble concentrating on things, such as reading the 0-No GO TO Q 8.1 18 newspaper or watching television 1-Yes 19 How often do you felt over the last two weeks? 1-several days 20 2-Morethan half of the days 21 3-Nearly every day 22 23 8.1 Moving or speaking so slowly that other people could 0-No GO TO Q 8.2 24 have noticed 1-Yes 25 How often do you felt over the last two weeks? 1-several days 26 2-Morethan half of the days 27 3-Nearly every day 28 8.2. Moving or speaking so loudly, fidgety or restless that 0-No GO TO Q 9 29 you have been moving around a lot more than usual that 1-Yes 30 other people could have noticed 31 How often do you felt over the last two weeks? 1-several days 32 2-Morethan half of the days http://bmjopen.bmj.com/ 33 3-Nearly every day 34 9 Thoughts that you would be better off dead or of hurting 0-No 35 yourself in some way 1-Yes 36 How often do you felt over the last two weeks? 1-several days 37 2-Morethan half of the days 38 39 3-Nearly every day

40 10. If you checked off (Q1-9) any problems, how difficult 0. Not difficult at all on September 25, 2021 by guest. Protected copyright. 41 have those problems made it for you to do your work, 1. Somewhat difficult 42 take care of things at home, or get along with other 2. Very difficult 43 people? 3. Extremely difficult 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 13 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 37 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 4.4 . Participants Sleep disorder 4 5 The following questions ask about any trouble Sleeping you may experience from your cancer within 6 the last 4 weeks. This may be resulted from surgery for cancer, pain from cancer treatments 7 (chemotherapy or radiation), or the disease itself. Please remember to answer these questions about 8 cancer related sleep disorder only 9 10 11 S.N Question Response Remarks 12 13 1. During the last 4 weeks, have you ever 1. Yes If “No skip” to 4.5 14 had trouble sleeping because of your 2. No 15 cancer 16 2. If yes, what Fordo you think peer the reason review of 1. Pain from only the Lesion of 17 your trouble sleep? the cancer cite 18 2. The surgical procedure 19 3. Drug side effect 20 4. Fear of metastasis 21 88. Other; specify______22 3. Have you taken medicine (prescribed or 0- No If “No” skip to Q6 23 over the counter) to help you sleep? 1- Yes 24 25 4. If yes, how often do you take the 1.less than once a week 26 medicine? 2. 1 to 2 times a week 27 3. 3 to 5 times a week 28

29 4. Daily 30 31

32 4.5. Physical activity of the participants http://bmjopen.bmj.com/ 33 The following questions ask about any trouble in physical activities, and day to day work you may 34 experience from your cancer within the last 4 weeks. 35 1 About your Health and Activities Never Almost Never Some- Often Almost 36 (PROBLEMS WITH…) times Always 37 1.1 Have you felt hard to walk a 0 1 2 3 4 38 distance of more than one bus 39 terminal? 40 1.2 Have you had difficulty to lift 0 1 2 3 4 on September 25, 2021 by guest. Protected copyright. 41 something heavy? 42 1.3. Have you had difficulty to take a 0 1 2 3 4 43 bath or shower by yourself? 44 The following three questions are to participants who have a job or student. If the participant 45 46 has no outdoor job or she is not student go to section part 5 47 2 About your Work/Studies Never Almost Never Some- Often Almost 48 (PROBLEMS WITH…) times Always 49 2.1 I have trouble keeping up with my 0 1 2 3 4 50 work or studies 51 2.2 Have you had missed work or 0 1 2 3 4 52 school because of not feeling well? 53 2.3 Have you had missed work or 0 1 2 3 4 54 school to go to the doctor or 55 hospital? 56 57 58 14 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 38 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Part 5. Address the following questions by measuring appropriately 4 5 6 1 Weight of the respondent (please measure her weight _____ kg 7 appropriately) 8 9 2 Height of the participant (please measure her weight ______cent meter 10 appropriately) 11 12 13 14 Thank you for your time!! 15 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 15 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 39 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 Breast Cancer Patient Survey - II 4 5 Questionner ID. ______Date of interview: _____/_____/______6 7 Patient’s Medical Record No. ______Participant’s phone number: ______8 9 Primary relative’s phone number: ______relationship: ______10 11 12 Name of interviewer: Dr/ Mr. /Mrs./Miss: ______Date: _____/_____ / _____ 13 14 15 Supervisor: 16 Dr/ Mr. /Mrs./Miss: ______For peer review signature: ______only Date: ___ / ___ /____ 17 18 19 2. 1. Treatment status of BC patients 20 Q. N Statements Choices Remarks 21 101. Have you received any treatment for 0. No Q204 22 you cancer? 1. Yes 23 24 102. If yes, what kind of treatments you 1. Surgery to remove the cancer 25 have received? 2. Chemotherapy 26 (multiple answer is possible) 3. Radiation therapy 27 4. Hormone therapy 28 29 88. Other forms of treatment; specify: 30 ______31 103. Where (in which facility) did you 32 receive these treatments? http://bmjopen.bmj.com/ 33 34 35 104. Since you were diagnosed with the 0. No Q201 36 disease, were you unable to receive 1. Yes 37 any form of treatments 38 39 105. What was the main reason for you 1. Could not afford the price of the 40 not receiving the treatment? treatment on September 25, 2021 by guest. Protected copyright. 41 2. Treatment not locally available 42 Multiple response is possible 3. Waited too long to get it 43 4. Difficulty in getting appointments 44 45 5. Do not like or trust or believe in 46 doctors 47 6. Insurance did not cover 48 7. Did not know where to go for 49 treatment 50 88. Others; specify ______51 52 53 54 55 56 57 58 16 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 40 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 2.2. Participants practice of traditional medicine to treat or relieve the symptoms of their CANCER 4 (after they have diagnosed) 5 S.N Question Choices Remark 6 7 201. Have you seen a traditional healer other 0. No Q301 8 than your regular doctors? 1. Yes 9 202. If yes, what type of healer did you see? 1. Herbalist 10 2. Spiritual healer 11 88. Other, specify 12 ______13 203. What is your main reason for using this 1. To treat my cancer 14 therapy? 2. To lessen the side effects of 15 cancer treatment 16 Multiple answerFor is possible peer review3. To relieve symptomsonly of my 17 18 cancer 19 4. To relieve stress 20 88. Other: specify: 21 ______22 204. How much would you estimate your or ______birr 23 your family have been spending per 24 month for these healers/ herbs/ or other 25 therapies? 26 27 205. Is your doctor aware that you are using 0. No 28 this therapy? 1. Yes 29 99. I do not know 30 31

32 2.3. Participants adherence to chemotherapy and hormonal therapy http://bmjopen.bmj.com/ 33 S. N Questions Choices Remarks 34 301. Have you taken chemotherapy? 0. No Q 305 35 1. Yes 36 302. If yes, how many cycles did your doctor ______number 37 38 ordered? 99. I do not know 39 303. Did you finish all the cycles? 0. No

40 1. Yes Q305 on September 25, 2021 by guest. Protected copyright. 41 304. 1. I forget to keep treatment appointments 42 If no, what are the main reasons? 2. I could not tolerate the side effects 43 3. I could no longer afford the treatment 44 4. I did not trust the effectiveness of the 45 medicine 46 5. The drug was not available 47 2. Others, specify 48 ______49 305. Are you taking hormonal therapy? 0. No Q 401 50 1. Yes 51 306. ______52 For how long did your doctor tell you to 53 take the drug? 54 307. Have you ever missed taking your 0. No Q401 55 hormonal therapy? 1. Yes 56 57 58 17 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 41 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 308. ______times 4 If yes, how often you missed? 5 6 309. If yes, for how long you missed? ______7 8 310. What was your main reason for missing 1. Side-effects 9 taking the drug? 2. Financial 10 3. Drug not available 11 12 4. I forget to take 13 88. Others, specify 14 ______15 16 2.4. Participants historyFor of medical peer cost for cancerreview treatment only 17 Q.N Question Choices Remark 18 19 401. Do you have any health insurance that covers your 0. No Q403 20 medical expense? 1. Yes 21 402. If yes, how much percent of your medical expense ______% 22 is covered by insurance 23 403. Do you have free medical service card? 0. No Q406 24 1. Yes 25 404. Were there any tests or treatments (including 0. No Q406 26 prescription medication for treatment or side 1. Yes 27 28 effects) that your doctor recommended for cancer 29 that your free service card did not cover? 30 405. What were the services you did not get for free? 1. ______31 Multiple response possible 2. ______

32 3. ______http://bmjopen.bmj.com/ 33 406. Because of your cancer, its treatment or the lasting 1. Medical expenses (medicine, 34 effects of that treatment, did you have any costs medical equipment) 35 you had to pay out of your own pocket in the 2. Transportation 36 following categories? 3. I had no out-of-pocket costs 37 Multiple response possible 4. I do not know/I am not sure 38 88. Others: Specify 39 ______40 on September 25, 2021 by guest. Protected copyright.

41 42 407. Can you estimate your out-of-pocket cost? 0. No Q409 43 1. Yes 44 408. If yes, how much? 1. Diagnosis ______Br 45 2. Treatment ______Br 46 3. Follow up ______Br 47 409. Were there any tests or treatments that your doctor 0. No Q411 48 recommended for your CANCER that you did not 1. Yes 49 get because you were unable to pay for them? 50 410. What tests or treatments were those? SPECIFY 1.______51 (FREE TEXT) 2.______52 3.______53 411. Have you ever forced to sell your property for 0- No Q413 54 covering the medical cost of cancer treatment, or 1- Yes 55 lasting effects of treatment 56 57 58 18 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 42 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 412. If yes, what type of property did you sell? 4 ______5 6 7 413. Have you or has anyone in your family had to 0. No Q415 8 borrow money or go into debt because of your 1. Yes 9 cancer, its treatment, or the lasting effects of that 10 treatment? 11 414. How much did you or your family borrow, or how ______birr 12 much debt did you incur because of your cancer, its 13 treatment, or the lasting effects of that treatment? 14 415. What is your average cost you spend per month for ______Birr 15 transportation related to your cancer? 16 416. Have you ever worriedFor about peer your family’s review 0. No only 17 financial stability because of your cancer, its 1. Yes 18 treatment or lasting effects of that treatment? 19 417. What is your current employment situation? Choice 1. Full time employed 20 21 only one 2. Part-time employed 22 3. Self-employed 23 4. On leave with pay 24 5. On leave without pay 25 6. Not employed-disabled 26 7. Retired 27 8. Homemaker 28 88. Others; specify ______29 418. Were you employed, when you were diagnosed with 0. No Q427 30 cancer? 1. Yes 31 419. At any time since your first cancer diagnosis, did 0. No Q427 32 you take extended paid time off from work, unpaid 1. Yes http://bmjopen.bmj.com/ 33 time off, or make a change in your hours, duties or 34 employment status? 35 420. When did you take extended paid time off from 1. At the time of diagnosis 36 work? 2. During treatment 37 38 Multiple response possible 3. After treatment 39 421. Did you ever change from working full-time to 0. No

40 working part-time or change to a less demanding 1. Yes on September 25, 2021 by guest. Protected copyright. 41 job? 42 422. Did you ever change from a set work schedule, 0. No 43 where you start and end at the same time every day, 1. Yes 44 to a flexible work schedule, where your start and end 45 times vary from day-to-day? 46 423. Because of your cancer, its treatment, or its lasting 0. No 47 effects, did you ever decide not to pursue an 1. Yes 48 advancement or promotion? 49 424. Because of your cancer, its treatment, or its lasting 0. No 50 effects, did you retire earlier than you had planned? 1. Yes 51 425. Did you lose any earning as a consequence of your 0. No Q427 52 cancer diagnosis? 1. Yes 53 54 426. If yes, how much money do you lost per month ______Birr 55 56 57 58 19 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 43 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 427. Since the time you were first diagnosed with cancer, 0. No Q501 4 has any friend or family member provided care to 1. Yes 5 you during or after your cancer treatment? 6 428. Who was your caregiver? 1. Spouse/partner 7 2. Child 8 9 3. Sibling 10 4. Parent 11 5. Other relative 12 6. Friend 13 88. Other, specify ______14 429. Because of your cancer, its treatment, or the lasting 0. No Q501 15 effects of that treatment, did any of your caregivers 1. Yes 16 ever take extendedFor paid time peer off from work, review unpaid 2. onlyNone of my caregivers were 17 time off, or make a change in their hours, duties or employed 18 employment status? 99. I do not know 19 430. If yes how much money did he/she lost per month? ______Birr 20 431. Did any of your caregivers ever take extended paid 0. No 21 time off from work, unpaid time off, or make a 1. Yes 22 change in their hours, duties, or employment status 99. I do not know 23 for at least 2 months? 24 25 26 2.5. Cancer patients’ survivorship care 27 S.N Question Choices Remarks 28 501. Do you have a regular follow-up? 0. No 29 1. Yes 30 502. Did your doctor tell you to have a 0. No 31 regular follow-up? 1. Yes 32 503. Since your cancer diagnosis, has your 1. Dietician or nutritionist http://bmjopen.bmj.com/ 33 doctor or a member of your health 2. Physical and or occupational therapist 34 care team ever referred you to any of 3. Mental health professional (psychiatrist, 35 the following specialties? psychologist, marriage or family therapist) 36 Mark all that apply 4. Social worker 37 38 5. Spiritual counselor 39 6. I have never been referred to any health specialists

40 88. Other specify ______on September 25, 2021 by guest. Protected copyright. 41 504. Since your cancer diagnosis, have 1. Screening for cervical cancer 42 you had any of the following cancer 2. Mammogram for breast lump 43 screening tests? 3. I did not have it 44 Mark all that apply 88. Other specify: ______45 46

47 48 49 50 51 52 53 54 55 56 57 58 20 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 44 of 45 BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 2.6. Depression 4 5 Over the past 2 weeks, how often have you been bothered by any of the following problems? 6 Instruction: Several days (2-6 days), more than half of the days (7-11days), nearly every day (12-14days) 7 S.N About your feeling (PROBLEMS WITH…) Response Remarks 8 1. Does your interest or pleasure in doing things was 0-No GO TO Q 2 9 decreased so much 1-Yes 10 11 How often do you felt over the last two weeks? 1-several days 12 2-Morethan half of the days 13 3-Nearly every day 14 2. Feeling down, depressed or hopeless 0-No GO TO Q 3.1 15 1-Yes 16 How often do youFor felt over peerthe last two weeks? review 1 -onlyseveral days 17 2-Morethan half of the days 18 3-Nearly every day 19 3.1 Trouble falling asleep or staying asleep 0-No GO TO Q 3.2 20 1-Yes 21 22 How often do you felt over the last two weeks? 1-several days 23 2-Morethan half of the days 24 3-Nearly every day 25 3.2 Trouble by a sleeping too much 0-No GO TO Q 4 26 1-Yes 27 How often do you felt over the last two weeks? 1-several days 28 2-Morethan half of the days 29 3-Nearly every day 30 4. Feeling tired or having little energy 0-No GO TO Q 5.1 31 1-Yes 32 http://bmjopen.bmj.com/ How often do you felt over the last two weeks? 1-several days 33 34 2-Morethan half of the days 35 3-Nearly every day 36 5.1 Poor appetite 0-No GO TO Q 5.2 37 1-Yes 38 How often do you felt over the last two weeks? 1-several days 39 2-Morethan half of the days

40 3-Nearly every day on September 25, 2021 by guest. Protected copyright. 41 5.2 Overeating 0-No GO TO Q 6 42 1-Yes 43 How often do you felt over the last two weeks? 1-several days 44 2-Morethan half of the days 45 3-Nearly every day 46 6. Feeling bad about yourself-or that you are a failure or 0-No GO TO Q 7 47 have let yourself or your family down 1-Yes 48 49 How often do you felt over the last two weeks? 1-several days 50 2-Morethan half of the days 51 3-Nearly every day 52 7. Trouble concentrating on things, such as reading the 0-No GO TO Q 8.1 53 newspaper or watching television 1-Yes 54 How often do you felt over the last two weeks? 1-several days 55 2-Morethan half of the days 56 3-Nearly every day 57 58 21 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 45 of 45 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027034 on 9 April 2019. Downloaded from 1 2 3 8.1 Moving or speaking so slowly that other people could 0-No GO TO Q 8.2 4 have noticed 1-Yes 5 How often do you felt over the last two weeks? 1-several days 6 2-Morethan half of the days 7 3-Nearly every day 8 9 8.2. Moving or speaking so loudly, fidgety or restless that 0-No GO TO Q 9 10 you have been moving around a lot more than usual that 1-Yes 11 other people could have noticed 12 How often do you felt over the last two weeks? 1-several days 13 2-Morethan half of the days 14 3-Nearly every day 15 9. Thoughts that you would be better off dead or of hurting 0-No GO TO Q 10 16 yourself in some Forway peer review1 -onlyYes 17 How often do you felt over the last two weeks? 1-several days 18 2-Morethan half of the days 19 3-Nearly every day 20 10. If you checked off (Q1-9) any problems, how difficult 0. Not difficult at all 21 have those problems made it for you to do your work, 1. Somewhat difficult 22 take care of things at home, or get along with other 2. Very difficult 23 24 people? 3. Extremely difficult 25 26 Is there anything else you would like to tell us about your experiences with cancer?” 27 28 ______29 30 ______31

32 http://bmjopen.bmj.com/ 33 Thank you for participating in this important study! 34 35 36 37 38 39

40 on September 25, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 22 | P a g e 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml