Bond University DOCTORAL THESIS Preventing Overdiagnosis Moynihan, Raymond Award date: 2016 Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. Preventing Overdiagnosis A thesis submitted in total fulfilment of the requirements of the degree of Doctor of Philosophy Raymond Noel Moynihan Centre for Research in Evidence-Based Practice, Faculty of Health Sciences and Medicine, Bond University, Australia February 2015 Preventing Overdiagnosis 2 Preventing Overdiagnosis Summary Background Medicine’s ability to help the sick is being challenged by its propensity to harm the healthy. As part of broader evidence and concern about too much medicine,[1] overdiagnosis is being increasingly recognised as a cause of harm and waste.[2] Overdiagnosis occurs when people are diagnosed with a disease that won’t harm them, commonly as a result of screening programmes detecting non-progressive diseases, such as indolent cancers. More broadly defined, overdiagnosis happens when expanding disease definitions label more people with milder symptoms or at lower risks, for whom a label and treatment may do more harm than good. Aims The thesis aimed to research the nature and causes of overdiagnosis, the mechanisms by which disease definitions are expanding, public awareness of overdiagnosis, and possible policy responses. Methods Several different methods were employed for a range of related research. An initial scoping of the literature was undertaken to prepare an overview. A cross-sectional study investigated how influential expert panels were changing definitions of common conditions. Arising from the scoping and the study, chronic kidney disease was selected and examined according to an explicit template, to learn more about how controversial definitions are expanded and defended. A questionnaire was developed and piloted, and a national quantitative survey conducted. A qualitative study analysed themes emerging from community responses to an open-ended question about the meaning of overdiagnosis. Results The initial literature scoping identified considerable evidence for overdiagnosis and potential drivers.[3] The cross-sectional study found among 16 expert panel publications, 10 widened definitions, 1 narrowed, and for 5, it was unclear.[4] No panel reported on potential for overdiagnosis, and of those panels making disclosures, 75% of members had multiple financial ties to companies with direct interests in broadened patient populations, contrary to Institute of Medicine, IOM, recommendations.[5,6] The case study found against a backdrop of sustained criticism, the controversial expansion of chronic kidney disease was 3 Preventing Overdiagnosis repeatedly defended by conflicted experts.[7] The survey found a minority of respondents (10%) - including those screened for prostate,(18%) and breast cancer,(10%) - reported they’d been informed about overdiagnosis, and a majority(78%) felt it inappropriate disease- defining panels had ties to companies.[8] A qualitative analysis of responses to “what do you think the term overdiagnosis means?” found 40% of participants had approximate understandings, 24% thought it meant overuse, and none mentioned screening.[9] Discussion and Implications A greater sensitivity to the problem of overdiagnosis is required in running and reporting on primary studies of tests and treatments, the production of systematic reviews, and proposals to change disease definitions.[10] Findings of endemic conflicts in panels setting diagnostic thresholds, in direct contrast to IOM and public antipathy, suggest a need for more independent and representative panels, informed by evidence about benefits and potential harms, including overdiagnosis. Survey findings reinforce the need for more information about overdiagnosis, particularly with screening. Recommendations include: (i) synthesising existing overdiagnosis evidence into an accessible repository; (ii) further investigating expanding disease definitions; (iii) reforming disease definition processes; (iv) initiating new international collaborations to further understand and combat overdiagnosis. References for Summary 1. Glasziou P, Moynihan R, Richards T, Godlee F. Too much medicine: too little care. BMJ. 347:f4247. doi: 10.1136/bmj.f4247 2. Welch G, Schwartz L, Woloshin S. Overdiagnosed: making people sick in pursuit of health. Boston: Beacon Press; 2011. 3. Moynihan R, Doust J, Henry D. Preventing overdiagnosis: how to stop harming the healthy. BMJ. 2012;344:e3502. 4. Moynihan RN, Cooke GP, Doust JA, Bero L, Hill S, Glasziou P. Expanding disease definitions in guidelines and expert panel ties to industry: a cross-sectional study of common conditions in the United States. PLoS Med. 2013;10:e1001500. doi: 10.1371/journal.pmed.1001500 5. Lo B, Field MJ. Conflict of interest in medical research, education, and practice. (Summary). Washington (D.C.): Institute of Medicine National Academies of Science; 2009 6. IOM. (Institute of Medicine) Clinical practice guidelines we can trust. Washington (D.C.): The National Academies Press; 2011 4 Preventing Overdiagnosis 7. Moynihan R, Glassock R, Doust J. Chronic kidney disease controversy: how expanding definitions are unnecessarily labelling many people as diseased. BMJ. 2013;347:f4298. 8. Moynihan R, Nickel B, Hersch, J, Beller E, Doust J, Compton S, et al. Public opinions about overdiagnosis: a national community survey. In Press, PLOS ONE, May 20, 2015. 9. Moynihan R, Nickel B, Hersch J, Doust J, Barratt A, Beller E, McCaffery K. What do you think overdiagnosis means?: a qualitative analysis of responses from a national community survey of Australians. In Press, BMJ Open, 2015. 10. Moynihan R, Henry D, Moons KGM. Using Evidence to Combat Overdiagnosis and Overtreatment: Evaluating Treatments, Tests, and Disease Definitions in the Time of Too Much. PLoS Med. 2014;11(7): e1001655. doi:10.1371/journal.pmed.1001655 5 Preventing Overdiagnosis 6 Preventing Overdiagnosis Declaration and Addendum This thesis is submitted to Bond University in fulfilment of the requirements of the degree of Doctor of Philosophy. This thesis represents my own original work towards this research degree and contains no material which has been previously submitted for a degree or diploma at this University or any other institution, except where due acknowledgement is made. Ray Moynihan is the sole author on the Introduction and Discussion chapters, 1 and 8, and lead author on all other chapters, which are substantially unchanged multi-author papers. The original research work underpinning all chapters was driven in every case primarily by Ray Moynihan, who also produced initial drafts of each manuscript, and managed all aspects of the collaborative research projects. None of the work submitted in this thesis was carried out before the PhD candidature. All permissions to reproduce figures, graphs or illustrations are noted within chapters, and their numbering has been modified when aggregating published papers into the full length manuscript. Referencing is consistent with Vancouver style, and original references which appeared in the published papers have been slightly modified to reflect this. In a very small number of cases web links which were cited in references in the thesis published papers are no longer active. As per university rules, where a substantially unchanged multi-author paper is included in the thesis a statement appears at the end of the chapter outlining the contributions of all involved, and these statements have been signed by all authors. 7 Preventing Overdiagnosis 8 Preventing Overdiagnosis Acknowledgments Immeasurable gratitude is owed to my indefatigable supervisors, Paul Glasziou and Jenny Doust, who have been a constant source of inspiration, encouragement, collegiality and support through the development and delivery of this thesis. A special thank you goes to all my other colleagues at the Centre for Research in Evidence- Based Practice at Bond University, for their on-going enthusiasm for the thesis subject matter and their support and laughter, including, but not limited to, Chris Del Mar, Tammy Hoffmann, Rae Thomas, Elaine Beller, Chrissy Erueti and Sarah Thorning. I’d also like to acknowledge all the administrative, academic, management, library and other staff at Bond, who’ve helped facilitated my research, and helped make my time during the thesis so enjoyable and productive. I’m also indebted to colleagues, collaborators and friends who’ve offered advice, encouragement and guidance, including David Henry, Geoff Morgan, Alexandra Barratt, Kirsten McCaffery, Jolyn Hersch and Brooke Nickel. And finally, a very loving thank you to my partner Miranda Burne, for bearing with me through the running of this academic marathon, and to my new son Louis, for his smiles and laughter that helped to propel me across the finish line. 9 Preventing Overdiagnosis 10 Preventing Overdiagnosis Peer-reviewed journal articles arising from this thesis • Moynihan R, Doust J,