1. Avoiding waste in research: the role of public involvement Iain Chalmers Coordinator James Lind Initiative NCRN Consumer Liaison Group Meeting Leeds, 25 June 2013

3. better, more equal

5. ‘The Liberati Manifesto’, 2011

7. Reasons for wanting to participate in clinical trials Self-interest, albeit with some altruism thrown in

9. (2012)

12. 7 2001-2005 1977-1985

15. Patients 1 Demand clinical trials addressing unanswered questions important to you 2 Demand and help to reduce waste in research Patients 1 Demand clinical trials addressing unanswered questions that are important 2 Demand reduced waste in research

16. 1 Demand clinical trials addressing unanswered questions that are important 2 Demand reduced waste in research

17. To promote Priority Setting Partnerships involving patients and clinicians to identify and promote their shared priorities for therapeutic research The UK Database of Uncertainties about the Effects of Treatments To publish uncertainties about the effects of treatments which cannot currently be answered by referring to relevant and reliable, up-to-date systematic reviews of existing research evidence

18. JLA Priority Setting Partnerships CompletedCurrent Asthma Urinary incontinence Vitiligo Prostate cancer Schizophrenia Type 1 diabetes ENT aspects of balance Life after stroke Eczema Tinnitus Cleft lip and palate Lyme disease Acne Childhood disability Dementia Dialysis Head and neck cancer Inflammatory bowel disease Multiple sclerosis Pressure ulcers Pre-term birth Sight loss and vision Skin - Hidradenitis Suppurative Hips and Knees - surgical interventions Spinal Cord Injury Palliative Care

19. Involving patients, carers and clinicians in research priority setting The JLA’s principles Inclusive Balance of perspectives Accessible to all Supportive Recognising a range of capacities and skills Transparent and democratic Data sharing Agreed protocol Declaration of interests Neutral facilitation Communication and feedback

20. Research priority themes [across asthma, incontinence, vitiligo, eczema, stroke, prostate cancer, schizophrenia, aspects of balance, and type 1 diabetes] Assessment of long-term effects (wanted and unwanted) of treatments Assessment of safety and adverse effects of treatments Assessment of complementary and non-prescribed treatments Assessment of strategies to improve early diagnosis and treatments, and harmonisation of practice Assessment of the effectiveness and safety of self- care

21. Interventions mentioned in research priorities identified by James Lind Alliance patient-clinician Priority Setting Partnerships, and among registered trials, 2003-2012. (Crowe et al. forthcoming)

22. www.jla.nihr.ac.uk

23. Measuring outcomes that matter to patients

24. Which outcomes of the effects of treatments do cancer patients rate as most important to them? Cure Life expectancy Freedom from symptoms Quality-Adjusted Life Years (QALYs) Tumour size X-rays/MRI images Blood/urine test results

27. 1 Demand clinical trials addressing unanswered questions that are important 2 Demand reduced waste in research

28. Low priority questions addressed Important outcomes not assessed Clinicians and patients not involved in setting research agendas Questions relevant to clinicians & patients? Over 50% studies designed without reference to systematic reviews of existing evidence Over 50% of studies fail to take adequate steps to reduce biases, e.g. unconcealed treatment allocation Appropriate design and methods? Over 50% of studies never published in full Biased under- reporting of studies with disappointing results Accessible full publication? Over 30% of trial interventions not sufficiently described Over 50% of planned study outcomes not reported Most new research not interpreted in the context of systematic assessment of other relevant evidence Unbiased and usable report? 50 % 85% Research waste = over $85 Billion / year 50 %

29. Overall conclusion: Patients are suffering and dying unnecessarily because of avoidable waste in research.

30. Low priority questions addressed Important outcomes not assessed Clinicians and patients not involved in setting research agendas Questions relevant to clinicians & patients? Over 50% studies designed without reference to systematic reviews of existing evidence Over 50% of studies fail to take adequate steps to reduce biases, e.g. unconcealed treatment allocation Appropriate design and methods? Over 50% of studies never published in full Biased under- reporting of studies with disappointing results Accessible full publication? Over 30% of trial interventions not sufficiently described Over 50% of planned study outcomes not reported Most new research not interpreted in the context of systematic assessment of other relevant evidence Unbiased and usable report? 50 % 85% Research waste = over $85 Billion / year 50 %

31. S ources of waste in deciding what research to do Studies designed without reference to systematic reviews of existing evidence, published and unpublished

33. Analysis of Introduction sections of all reports of controlled trials in May 2009 and May 2012 in Lancet, New Eng J Med, BMJ, JAMA, & Ann Int Med (Clarke et al. forthcoming) 2009 (n=29) 2012 (n=35) First trial addressing the question 55 Contains an updated systematic review, which was used to inform the design of a new trial 11 Discusses a relevant systematic review, which was not used to inform the design of a new trial 1013 Refers to other randomized trials 410 Although not first trial, does not refer to other randomized trials 96

34. "It is essential that existing sources of evidence, especially systematic reviews, are considered carefully prior to undertaking research… Research which duplicates other work unnecessarily, or which is not of sufficient quality to contribute something useful to existing knowledge, is in itself unethical." (Department of Health 2001)

36. Sometimes the most important advances in knowledge come from analyses of existing evidence

39. Low priority questions addressed Important outcomes not assessed Clinicians and patients not involved in setting research agendas Questions relevant to clinicians & patients? Over 50% studies designed without reference to systematic reviews of existing evidence Over 50% of studies fail to take adequate steps to reduce biases, e.g. unconcealed treatment allocation Appropriate design and methods? Over 50% of studies never published in full Biased under- reporting of studies with disappointing results Accessible full publication? Over 30% of trial interventions not sufficiently described Over 50% of planned study outcomes not reported Most new research not interpreted in the context of systematic assessment of other relevant evidence Unbiased and usable report? 50 % 85% Research waste = over $85 Billion / year 50 %

40. Alessandro Liberati

42. Proportion (%) of clinical trials registered by 1999 and published by 2007 (from Ross et al. PLoS Med 2009;6(9): e1000144). Country Size Phase Funder UK HTA program

44. www.alltrials.net

45. “(It) is my belief that by taking part in research, I will help other patients in future. For that to happen, the results of the research must be made available. Even if the research isn't finished or the results aren't as expected, the data and information are still of value and should be made available…. Patients become participants to add to knowledge and to eliminate uncertainties. Hiding results, no matter what the reason, isn't in that spirit at all.” Richard Stephens, 12 June 2013

46. In summary, patients should require the research community: to seek help from patients in selecting questions to address in research to review existing evidence systematically before planning new research to publish the results of research, whatever their direction or strength

47. What are patient groups doing to address these problems?

48. Be more discriminating about what research and which clinical trials to support

49. BMJ 2010;340:c725

51. Chalmers I. Lancet 2000;356:774

53. www.testingtreatments.org

55. Promote research on the effects of treatments…

56. …but only if it meets scientific and ethical principles Promote research on the effects of treatments…

57. better, more equal