Summary Report

Home , Amebicide, Diiodohydroxyquinoline

Item Type Report

Authors Yoon, SeJeong; Gianturco, Stephanie L.; Pavlech, Laura L.; Storm, Kathena D.; Yuen, Melissa V.; Mattingly, Ashlee N.

Publication Date 2020-01

Keywords Diiodohydroxyquinoline; Compounding; Food, Drug, and Cosmetic Act, Section 503B; Food and Drug Administration; Outsourcing facility; Iodoquinol; Drug compounding; Legislation, Drug; United States Food and Drug Administration

Rights Attribution-NoDerivatives 4.0 International

Download date 25/09/2021 22:44:46

Item License http://creativecommons.org/licenses/by-nd/4.0/

Link to Item http://hdl.handle.net/10713/12109 Summary Report

Diiodohydroxyquinoline

Prepared for: Food and Drug Administration Clinical use of bulk drug substances nominated for inclusion on the 503B Bulks List Grant number: 2U01FD005946

Prepared by: University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) University of Maryland School of Pharmacy

January 2020

This report was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award (U01FD005946) totaling $2,342,364, with 100 percent funded by the FDA/HHS. The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement by, the FDA/HHS or the U.S. Government.

Table of Contents

REVIEW OF NOMINATION ...... 4 METHODOLOGY ...... 4 Background information...... 4 Systematic literature review ...... 5 Outreach to medical specialists and specialty organizations ...... 7 Survey ...... 7 CURRENT AND HISTORIC USE...... 8 Summary of background information ...... 8 Summary of literature review ...... 8 Summary of focus groups/interviews of medical experts and specialty organizations ...... 13 Summary of survey results...... 14 CONCLUSION ...... 15 APPENDICES ...... 16 Appendix 1. References...... 16 Appendix 2. Survey instrument ...... 20

Table of Tables

Table 1. Participating associations ...... 7 Table 2. Associations that declined participation...... 8 Table 3. Currently approved products – US...... 8 Table 4. Currently approved products – select non-US countries and regions ...... 8 Table 5. Types of studies ...... 8 Table 6. Number of studies by country ...... 9 Table 7. Number of studies by combinations ...... 10 Table 8. Dosage by indication – US ...... 10 Table 9. Dosage by indication – non-US countries ...... 11 Table 10. Compounded products – US ...... 12 Table 11. Compounded products – non-US countries ...... 12 Table 12. Overview of interviewees ...... 13 Table 13. Characteristics of survey respondents ...... 14 Table 14. Types of products used, prescribed, or recommended ...... 14 Table 15. Compounded use of diiodohydroxyquinoline in practice ...... 14 Table 16. Indications for which diiodohydroxyquinoline is considered a standard therapy ...... 14 Table 17. Reasons for using compounded product instead of the FDA-approved products ...... 14 Table 18. Change in frequency of compounded diiodohydroxyquinoline usage over the past 5 years .....14 Table 19. Do you stock non-patient specific compounded diiodohydroxyquinoline in your practice? .....14 Table 20. Questions related to stocking non-patient specific compounded diiodohydroxyquinoline...... 14

REVIEW OF NOMINATION Diiodohydroxyquinoline (UNII code: 63W7IE88K8) was nominated for inclusion on the 503B Bulks List by the Outsourcing Facilities Association (OFA). While the exact medical condition for which the compounded product is being request is generally unknown, diiodohydroxyquinoline is generally used as an antifungal agent. Diiodohydroxyquinoline will be compounded as a topical product in a dosage form and strength based on the prescriber’s request; the therapeutic dose is 1%. Diiodohydroxyquinoline was nominated for use in combination with other active pharmaceutical ingredients (API), refer to Table 7 for the nominated combination formulations. Reasons provided for nomination to the 503B Bulks List include: • Patients respond differently and the compounded product may be the only formulation to effectively treat the indication for which it is intended to treat. • There are no FDA-approved products that contain diiodohydroxyquinoline. • Compounding from bulk ensures that only the ingredients necessary to achieve the desired clinical outcome are utilized avoiding any using fillers, excipients, binders, dyes, or preservatives that may be irritating, hazardous, or allergenic. • Commercially available finished products have an inherent variance in potency creating an uncertain final concentration for the new product.

METHODOLOGY Background information The national medicine registers of 13 countries and regions were searched to establish the availability of diiodohydroxyquinoline products in the United States (US) and around the world. The World Health Organization, the European Medicines Agency (EMA) and globalEDGE were used to identify regulatory agencies in non-US countries. The medicine registers of non-US regulatory agencies were selected for inclusion if they met the following criteria: freely accessible; able to search and retrieve results in English language; and desired information, specifically, product trade name, active ingredient, strength, form, route of administration (ROA) and approval status provided in a useable format. Based on these criteria, the medicine registers of 13 countries/regions were searched: US, Canada, European Union (EU), United Kingdom (UK), Ireland, Belgium, Latvia, Australia, New Zealand, Saudi Arabia, Abu Dhabi, Hong Kong, and Namibia. Both the EMA and the national registers of select EU countries (Ireland, UK, Belgium, and Latvia) were searched because some medicines were authorized for use in the EU and not available in a member country and vice versa. Each medicine register was searched for diiodohydroxyquinoline; name variations of diiodohydroxyquinoline were entered if the initial search retrieved no results. The following information from the search results of each register was recorded in a spreadsheet: product trade name; active ingredient(s); strength; form; ROA; status and/or schedule; approval date. Information was recorded only for products with strengths, forms and/or ROA similar to those requested in the nominations. In addition to the aforementioned medicine registers, the DrugBank database (version 5.1.4) and the Natural Medicines database were searched for availability of over-the-counter (OTC) products containing diiodohydroxyquinoline. The availability of OTC products (yes/no) in the US and the ROA of these products were recorded in a spreadsheet. Individual product information was not recorded.

Systematic literature review Search strategy Two databases (PubMed and Embase) were searched including any date through December 22, 2018. The search included a combination of (Diiodohydroxyquin[tiab] OR Iodoquinol[tiab] OR Diiodohydroxyquinoline[tiab] OR Diodoquin[tiab] OR Diquinol[tiab] OR "5,7-diiodoquinolin-8- ol"[tiab] OR diiodoquin[tiab]) AND (infect*[tiab] OR ameb*[tiab] OR antiparasitic[tiab] OR parasit*[tiab] OR protozoal*[tiab] OR derm*[tiab] OR skin[tiab] OR clinical[tiab] OR therapy[tiab] OR therapeutic*[tiab] OR treatment[tiab] OR anti*[tiab]) AND (humans[MeSH Terms] AND English[lang]) NOT autism. Peer-reviewed articles as well as grey literature were included in the search. Search results from each database were exported to Covidence®, merged, and sorted for removal of duplicate citations. Study selection Articles were not excluded on the basis of study design. Articles were considered relevant based on the identification of a clinical use of diiodohydroxyquinoline or the implementation of diiodohydroxyquinoline in clinical practice. Articles were excluded if not in English, a clinical use was not identified, incorrect salt form, or if the study was not conducted in humans. Screening of all titles, abstracts, and full-text were conducted independently by two reviewers. All screening disagreements were reconciled by a third reviewer. Data extraction A standard data extraction form was used to collect study authors; article title; year published; journal title; country; indication for diiodohydroxyquinoline use; dose; strength; dosage form; ROA; frequency and duration of therapy; any combination therapy utilized; if applicable, formulation of compounded products; study design; and any discussion surrounding the use of diiodohydroxyquinoline compared to alternative therapies. Results Please refer to Figure 1.

Figure 1. Summary of literature screening and selection (PRISMA 2009 Flow Diagram)

Outreach to medical specialists and specialty organizations Using the indication from the nomination and the results of the literature review, two (2) medical specialties that would potentially use diiodohydroxyquinoline were identified: dermatology and infectious disease. Semi-structured interviews were conducted with subject matter experts within these specialties. Interviews lasted from 30-75 minutes and were conducted either via telephone or in-person. Criteria for selecting subject matter experts included recommendations provided by specialty professional associations, convenient geographic location, authorship within the specialty, or referral by an interviewee. Up to nine (9) interviews were conducted per substance. Two (2) experts were contacted for interviews, of which two (2) accepted and zero (0) declined interviews. The interviews were recorded and transcribed via ©Rev.com. QSR International’s Nvivo 12 software was utilized for qualitative data analysis. The University of Maryland, Baltimore IRB and the Food & Drug Administration RIHSC reviewed the study and found it to be exempt. Subject matter experts provided their oral informed consent to participate in interviews.

Survey General professional medical associations and specialty associations for dermatology and infectious disease identified from the nomination, literature review, and interviews, were contacted to facilitate distribution of an online survey. A Google™ search was conducted to identify relevant professional associations within each specialty. Associations were included if their members are predominantly practitioners, national associations, and organizations focused on practice within the US. Organizations without practicing physicians and state or regional organizations were excluded. The association’s website was searched in order to identify the email of the executive director, regulatory director, media director, association president, board members, or other key leaders within the organization to discuss survey participation. If no contact information was available, the “contact us” tab on the association website was used. The online surveys were created using Qualtrics® software (Provo, UT). Survey links were distributed to four (4) associations. If an association had more than one (1) substance with indications relevant to that specialty, substances were combined into one (1) survey with no more than 14 substances per survey. Table 1 highlights the associations that agreed to distribute the survey link and Table 2 includes the associations that declined to participate. Additionally, single substance surveys were created and posted on the project website which was shared with survey participants. Participation was anonymous and voluntary. The estimated time for completion was 30 minutes with a target of 50 responses per survey. The Office of Management and Budget (OMB) approved this project.

Table 1. Participating associations

Specialty Association

American Academy of Dermatology (AAD) Dermatology American Society for Dermatologic Surgery (ASDS)

Table 2. Associations that declined participation

Specialty Association Reasons for Declining

American Medical Association (AMA) Failed to respond Medicine American Osteopathic Association (AOA) Failed to respond

CURRENT AND HISTORIC USE Summary of background information • Diiodohydroxyquinoline is not available as an FDA-approved product. • Diiodohydroxyquinoline is not available as an OTC product in the US. • There is a current United States Pharmacopeia (USP) monograph for diiodohydroxyquinoline. • Diiodohydroxyquinoline is available as a combination product in Hong Kong.

Table 3. Currently approved products – US No approved products in the US

Table 4. Currently approved products – select non-US countries and regions No approved products in the selected non-US countries and regions

Summary of literature review • Total number of studies included: 64 studies (45 descriptive, 11 experimental, and 8 observational). • Most of the studies were from the US (47). • The most common indication for the use of diiodohydroxyquinoline in both the US and non-US studies was amoebiasis. • Two (2) US studies were identified that utilized a compounded product with one (1) study utilizing a nominated dosage form.

Table 5. Types of studies

Types of Studies Number of Studies

Descriptive1–45 45

Experimental46–56 11

Observational57–64 8

Table 6. Number of studies by country

Country Number of Studies

Australia 19,34,57,62 4

Canada5,30 2

Egypt32 1

India 13,46 2

Iran56 1

Norway36 1

South Africa61 1

UK44 1

US1–3,6–12,14,16–18,20–29,31,33,35,38,40–43,45,47–55,58–60,63,64 47

West Indies15 1

Multiple Countries 2 • Taiwan, China4,39

Total US: 47 Total Non-US Countries: 17

Table 7. Number of studies by combinations

Combination Formula Number of Studies

Diiodohydroxyquinoline 1% / Aloe vera 0.5% / Fluocinolone acetonide 0.01% - Topical cream 0

Nominated Diiodohydroxyquinoline 1% / Aloe vera 0.5% / Fluocinolone acetonide 0.025% - Topical cream 0

Diiodohydroxyquinoline 1% / Hydrocortisone 2.5% / Ketoconazole 2% - Topical cream 0

Diiodohydroxyquinoline 350mg / Bacitracin 1000 units / Chloroquine diphosphate 50mg / Neomycin 4000 units - Tablet58 1

Diiodohydroxyquinoline 100mg / Diethylstilbestrol 0.1mg / Sulfadiazine 500mg - Vaginal suppository38 1 Others found in literature Diiodohydroxyquinoline 325mg / Metronidazole 200mg - Tablet46 1

Diiodohydroxyquinoline / Sodium propionate / Propionic acid - Suppository30 1

Table 8. Dosage by indication – US

Indication Dose Concentration Dosage Form ROA Duration of Treatment

210mg – 6.5g/day 650ng Tablet Oral 2 weeks-13 years Acrodermatitis enteropathica1,3,6,7,9,31,40–42 400ml/day – – – –

350mg - 3.6g/day 200-325mg Tablet Oral 7 days-6 months Amoebiasis (Entamoeba histolytica)8,10,11,16–18,20– 25,29,35,43,45,47,51–53,55,58,60,63 – 3- 10% Ointment Topical –

Balantidium coli45 1.95g/day – – – 14-21 days

Blastocystis hominis12,49,59 1.95g/day – – Oral 10-20 days

– 1-15% Ointment – – – Lotion Dermatoses22,26,48,54 Topical 2-3 teaspoons 10% Suspension 4-8 weeks – 5% Cream

• 30-40mg/kg/day Dientamoeba fragilis2,33,45,50,64 – – – 10-35 days • 1.8-1.95g/day

Isospora14 – – – – 20 days

200mg/day 100mg Tablet 6-8 weeks

Trichomonal vaginitis27,28,38 1 ounce 100mg/1g Powder Vaginal Once

200mg/day 100mg Suppository 7-12 days Abbreviations: “–“, not mentioned; ROA, route of administration.

Table 9. Dosage by indication – non-US countries

Indication Dose Concentration Dosage Form ROA Duration of Treatment

Acrodermatitis enteropathica19,32 500-1800mg/day – – – 2 months

310-1950mg/day 325mg Tablet Oral 10 days-9 months Amebiasis4,13,15,36,37,39,46,56,61 25-40mg/kg/day (max 2g/day) – – – 20-27 days

Balantidium coli13 40mg/kg/day – – – 20 days

Blastocystis app.62 1890mg/day – – – 20 days

650mg/day – – Oral 10-12 days Dientamoeba fragilis5,34,44,57 40mg/kg/day – – – 20 days

Trichomonal vaginitis30 3 suppositories – Suppositories Vaginal 15 days Abbreviations: “–“, not mentioned; ROA, route of administration.

Table 10. Compounded products – US

Publication Indication Compounding Method Dosage Form Final Strength Year

Amoebiasis 1949 • 3 different ointments made with 3 different bases: petrolatum, hydrophilic base, and aquaphor Ointment 3-10% (amebicide)22

Trichomonal • Diiodohydroxyquinoline 100mg, sulfadiazine 500 mg, diethylstilbestrol 0.1 mg, sodium lauryl sulfate 1955 Suppository 100mg vaginitis38 6.54mg, tartaric acid 6.0mg, boric acid 120mg, dextrose 0.66g, lactose 0.66g, lanolin 0.66g

Table 11. Compounded products – non-US countries No compounded products from reported studies

Summary of focus groups/interviews of medical experts and specialty organizations Two (2) interviews were conducted.

Table 12. Overview of interviewees

Level of Current Experience with Interviewee Specialty Interview Summary Response Training Practice Setting Diiodohydroxyquinoline

Dermatology/ Independent DER_05 MD It was used long time ago • There’s no use for it in office and there are other safer treatment options. Immunology Consultant

Infectious disease Inpatient, INF_01 MD No • “I can't think of any of the reason why I would need to use this” Internal medicine outpatient Abbreviation: MD, Doctor of Medicine.

Historic uses • One interviewee stated “Way back when, in my earlier days of taking care of patients, we could write prescriptions where this drug would've been a component of a prescription topical product. And it was used. But, as I pointed out, there were safety concerns raised about it, which led to it falling out of use.” Concerns • Peripheral neuropathy and optic toxicity. • Issue with pediatric use – in the 1980s, the Academy of Pediatric panel recommended eliminating the use of diiodohydroxyquinoline, particularly because there are other therapeutic options. • One interviewee stated “I would have concern about its safe use. And particularly on a bulk compounding. We have a lot of other options. We've got a lot more options since 1956 on.” Need for office use • One interviewee stated “There's a whole lot more of topical antifungal agents that are out there. And if somebody needed it for some reason, they could write a prescription for a patient to go get it. It's the in-office use that makes no sense as an antifungal. We don't treat fungal infections with a one-off application.”

Summary of survey results

Table 13. Characteristics of survey respondents [5 people responded to the survey]

Board Certification MD No Response

Dermatology 2 0

No Response 0 3 Abbreviation: MD, Doctor of Medicine.

Table 14. Types of products used, prescribed, or recommended No survey respondents reported using diiodohydroxyquinoline

Table 15. Compounded use of diiodohydroxyquinoline in practice No survey respondents reported using diiodohydroxyquinoline

Table 16. Indications for which diiodohydroxyquinoline is considered a standard therapy No survey respondents reported using diiodohydroxyquinoline

Table 17. Reasons for using compounded product instead of the FDA-approved products No survey respondents reported using diiodohydroxyquinoline

Table 18. Change in frequency of compounded diiodohydroxyquinoline usage over the past 5 years No survey respondents reported using diiodohydroxyquinoline

Table 19. Do you stock non-patient specific compounded diiodohydroxyquinoline in your practice? No survey respondents reported using diiodohydroxyquinoline

Table 20. Questions related to stocking non-patient specific compounded diiodohydroxyquinoline No survey respondents reported using diiodohydroxyquinoline

CONCLUSION Diiodohydroxyquinoline (UNII code: 63W7IE88K8) was nominated for inclusion on the 503B Bulks List by the Outsourcing Facilities Association (OFA). While the exact medical condition for which the compounded product is being request is generally unknown, diiodohydroxyquinoline is generally used as an antifungal agent. Diiodohydroxyquinoline will be compounded as a topical product in a dosage form and strength based on the prescriber’s request; the therapeutic dose is 1%. Diiodohydroxyquinoline is not approved in any of the foreign medicine registries searched as the nominated substance. From the literature review conducted, the most common indication in both the US and non-US studies was amoebiasis. One (1) US study used diiodohydroxyquinoline as a compounded product in one of the nominated dosage forms, however this study was completed in 1949. From the interviews, both interviewees did not see the need to use it in office because there are safer treatment options available and if someone needs it, they can write prescription. From the survey responses, zero (0) out of five (5) respondents reported the use of diiodohydroxyquinoline in practice.

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Appendix 2. Survey instrument Start of Block: Welcome Page The University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI), in collaboration with the Food and Drug Administration (FDA), is conducting research regarding the use of certain bulk drug substances nominated for use in compounding by outsourcing facilities under section 503B of the Federal Food, Drug, and Cosmetic Act. In particular, we are interested in the current and historic use of these substances in clinical practice. This survey is for diiodohydroxyquinoline. As a medical expert, we appreciate your input regarding the use of this substance in your clinical practice. This information will assist FDA in its development of a list of bulk drug substances that outsourcing facilities can use in compounding under section 503B of the Act. All responses are anonymous. OMB Control No. 0910-0871 Expiration date: June 30, 2022 The time required to complete this information collection is estimated to average 30 minutes, including the time to review instructions, search existing data sources, gather the data needed, and complete and review the information collection. An agency may not conduct or sponsor, and a person is not required to respond to a collection of information unless it displays a currently valid OMB control number. If you have additional questions or concerns about this research study, please email: [email protected]. If you have questions about your rights as a research subject, please contact HRPO at 410-760-5037 or [email protected]. End of Block: Welcome Page

Start of Block: Diiodohydroxyquinoline Q1. What type(s) of product(s) do you use, prescribe, or recommend for diiodohydroxyquinoline? Please check all that apply. ▢ Compounded drug product ▢ FDA-approved drug product ▢ Over the counter drug product ▢ Dietary supplement (e.g. vitamin or herbal supplement products sold in retail setting) ▢ Unsure Skip To: Q13 If What type(s) of product(s) do you use, prescribe, or recommend for diiodohydroxyquinoline? Please check all th... != Compounded drug product Skip To: Q2 If What type(s) of product(s) do you use, prescribe, or recommend for diiodohydroxyquinoline? Please check all th... = Compounded drug product

Display This Question: If What type(s) of product(s) do you use, prescribe, or recommend for diiodohydroxyquinoline? Please check all th... = Compounded drug product

Q2. Please list any conditions or diseases for which you use compounded diiodohydroxyquinoline in your practice. Please include the strength(s), dosing frequency(ies), dosage form(s), route(s) of administration, duration of therapy, and patient population (ex. age, gender, comorbidities, allergies, etc).

Strength(s) Dosing Dosage Route(s) of Duration Patient (please frequency(ies) form(s) administration of therapy population include units)

Condition 1 (please describe)

Condition 2 (please describe)

Condition 3 (please describe)

Condition 4 (please describe)

Condition 5 (please describe)

Q3. Do you use compounded diiodohydroxyquinoline as a single agent active ingredient, or as one active ingredient in a combination product? Please check all that apply. ▢ Single ▢ Combination Skip To: Q5. If Do you use compounded diiodohydroxyquinoline as a single agent active ingredient, or as one active ingredient... != Combination Display This Question: If Loop current: Do you use compounded diiodohydroxyquinoline as a single agent active ingredient, or as one active ingredient... = Combination Q4. In which combination(s) do you use compounded diiodohydroxyquinoline? Please check all that apply. ▢ Diiodohydroxyquinoline 1% / Aloe vera 0.5% / Fluocinolone acetonide 0.025-0.01% ▢ Diiodohydroxyquinoline 1% / Hydrocortisone 2.5% / Ketoconazole 2% ▢ Other (please describe) ______Q5. For which, if any, diseases or conditions do you consider compounded diiodohydroxyquinoline standard therapy?

______Q6. Does your specialty describe the use of compounded diiodohydroxyquinoline in medical practice guidelines or other resources? ______

Q7. Over the past 5 years, has the frequency in which you have used compounded diiodohydroxyquinoline changed? o Yes - I use it MORE often now (briefly describe why) ______o Yes - I use it LESS often now (briefly describe why) ______o No - use has remained consistent Q8. Why do you use compounded diiodohydroxyquinoline instead of any FDA-approved drug product? ______Q9. Do you stock non-patient-specific compounded diiodohydroxyquinoline in your practice location? o Yes o No Skip To: End of Block If Do you stock non-patient-specific compounded diiodohydroxyquinoline in your practice location? = No Display This Question: If Do you stock non-patient-specific compounded diiodohydroxyquinoline in your practice location? = Yes Q10. In what practice location(s) do you stock non-patient-specific compounded diiodohydroxyquinoline? Please check all that apply. ▢ Physician office ▢ Outpatient clinic ▢ Emergency room ▢ Operating room ▢ Inpatient ward ▢ Other (please describe) ______Q11. How do you obtain your stock of non-patient-specific compounded diiodohydroxyquinoline? Please check all that apply. ▢ Purchase from a compounding pharmacy ▢ Purchase from an outsourcing facility ▢ Compound the product yourself ▢ Other (please describe) ______Q12. Why do you keep a stock of non-patient-specific compounded diiodohydroxyquinoline? Please check all that apply. ▢ Convenience ▢ Emergencies ▢ Other (please describe) ______Skip To: End of Block If Why do you keep a stock of non-patient-specific compounded diiodohydroxyquinoline? Please check all that apply. = Convenience Skip To: End of Block If Why do you keep a stock of non-patient-specific compounded diiodohydroxyquinoline? Please check all that apply. = Emergencies Skip To: End of Block If Why do you keep a stock of non-patient-specific compounded diiodohydroxyquinoline? Please check all that apply. = Other (please describe) Q13. For which, if any, diseases or conditions do you consider diiodohydroxyquinoline standard therapy?

______Q14. Does your specialty describe the use of diiodohydroxyquinoline in medical practice guidelines or other resources? ______End of Block: Diiodohydroxyquinoline

Start of Block: Background Information Q15. What is your terminal clinical degree? Please check all that apply. ▢ Doctor of Medicine (MD) ▢ Doctor of Osteopathic Medicine (DO) ▢ Doctor of Medicine in Dentistry (DMD/DDS) ▢ Naturopathic Doctor (ND) ▢ Nurse Practitioner (NP) ▢ Physician Assistant (PA) ▢ Other (please describe) ______Q16. Which of the following Board certification(s) do you hold? Please check all that apply. ▢ No Board certification ▢ Allergy and Immunology ▢ Anesthesiology ▢ Cardiovascular Disease ▢ Critical Care Medicine ▢ Dermatology ▢ Emergency Medicine ▢ Endocrinology, Diabetes and Metabolism ▢ Family Medicine ▢ Gastroenterology ▢ Hematology ▢ Infectious Disease ▢ Internal Medicine ▢ Medical Toxicology ▢ Naturopathic Doctor ▢ Naturopathic Physician ▢ Nephrology ▢ Neurology ▢ Obstetrics and Gynecology ▢ Oncology ▢ Ophthalmology ▢ Otolaryngology ▢ Pain Medicine ▢ Pediatrics ▢ Psychiatry ▢ Rheumatology

▢ Sleep Medicine ▢ Surgery (please describe) ______▢ Urology ▢ Other (please describe) ______End of Block: Background Information