Developing European clinical research in the interest of patients and public health

1. Developing European clinical research in the interest of patients and public health Kamran Abbasi Deputy editor, BMJ Brussels, May 2005

2. Legislation is not new • Research was conducted on the basis of good faith until the early 19th Century when a few researchers breached the trust of the people

3. Anatomy act 1832

4. Cruelty to animals act 1876

5. A question Is it likely to be in the public interest to make it more difficult to do research?

6. What’s the answer? We need a balance between the needs of research and the interests of patients

8. A neurologist’s view • Rightly or wrongly, clinical researchers are exhausted by the demands of ethics committees that seem more concerned with the science (which they cannot necessarily judge) and editorial control of patient information sheets than with ethics • Charles Warlow, BMJ 31 July 2004

10. Sir Richard Doll’s view • No one with the power to do anything will take any notice until a bona fide researcher is jailed for transgressing some trivial regulation

11. “I’ve transgressed a trivial regulation”

12. A trial of antihypertensive medication • The COREC form is 68 pages long, has 174 fields to fill in, requires up to eight signatures of authorisation, and takes over 40 hours to complete • David Wald, BMJ 31 July 2004

13. Goodbye to the paperless office

15. A research governance view • Only those who have full-time commitment to research can afford to embrace these new systems, leading to a greater separation between academic and clinical staff • Bentley and Enderby, BMJ 12 Feb 2005

17. A multi-centre survey of impact of endoscopy service innovations • Research studies requiring multiple NHS sites should build in substantial lag times before research processes can be initiated • We anticipate that failure to address this new obstacle to health service research will block evaluation work and accelerate the migration of clinical studies to other parts of the world • Elwyn et al, BMJ 9 April 2005

18. It isn’t all about research ethics and governance Other factors are at play to change the climate of clinical research in Europe

19. People power

20. A carer’s view • I know that some people with dementia and their carers perceive acceptable risk differently from ethics committees and are more willing to take risks, feeling there is little to lose • Nurock, BMJ 26 Feb 2005

21. Parliamentary power

22. Journal power?

23. Two thirds of trials in major journals are funded by the drug industry (Egger M, et al, BMJ 2001; 323: 773)

24. What is the problem? • Stern and Simes BMJ 1997;315:640-645 • Question: To what extent is publication influenced by study outcome? • Studies submitted to an Australian ethics committee over 10 years • Examined protocols • Questionnaire to authors (70% response)

25. Stern and Simes: results

26. Stern and Simes: conclusions • Positive trials are more likely to be submitted for publication • Positive trials are more likely to be published • Positive trials are more likely to be published quickly • Implications for systematic reviews and the scientific record • Important to register all trials

27. More evidence for the problem • Lexchin and Bero BMJ 2003;326:1167-70 • Question: Does drug industry sponsorship influence research quality and outcome? • Meta-meta-analysis • Industry research less likely to be published (more likely in symposium proceedings) • No difference in methodological quality • More likely to have a positive finding (OR 4.05 95% CI 2.98 to 5.51)

28. Lexchin and Bero • A wide range of diseases eg osteoarthiritis of the knee, multiple myeloma, psychiatric problems, Alzheimer’s disease, venous thromboembolism • A wide range of drugs eg tacrine, clozapine, 3rd generation OCP, erythropoietin, antidepressants, topical glucocorticoids, treatment for HIV

29. Even more evidence • Melander et al BMJ 2003;326:1171-3 • Question: Is there selective reporting of sponsored studies by drug companies? • Trials submitted to the Swedish drug regulatory authority (5 SSRIs, 42 trials) • Multiple publication • Selective publication • Selective reporting

30. Melander et al: conclusion • “Any attempt to recommend a specific selective serotonin reuptake inhibitor from the publicly available data ONLY is likely to be based on biased evidence.”

31. Moves towards greater transparency

32. Globalisation

33. Localisation

34. Weak loyalty?

35. Nation first

36. Medical Research Council review • Incorporation of EU trials directive into UK law • Passage of the Human Tissue Act (2004) • Concerns over the increasing requirements of research ethics committees • Great variation in implementation of regulations

37. The “market” is confused • What’s the difference between research and audit? • Do I require ethics committee approval for audit? • Different acts cover different regions eg the human tissue act does not apply in Scotland • Different countries may interpret EU laws differently • Different players: WHO, EU, national etc

38. Medical Research Council view (1) • In practice, regulation requires additional bureaucracy and costs, both in terms of money and time • Thus the intention of regulation to ensure high ethical standards may have the perverse effect of creating so many barriers that ethical research may be discouraged, even to the point where it may not take place, and this itself may be unethical

39. Medical Research Council view (2) • The barriers to participation by individuals may lead to poor research as those who participate may be systematically different from those who do not and thus lead to biased results • There is no easy solution to finding the right balance

40. What will drive change? Change = Burning platform x Vision x Next steps

41. You have a burning platform

42. But is your vision sufficiently clear?

43. An EFGCP view • European researchers need to decide what they want to save. Do they wish to pool their knowledge and resources in Europe? Or do they prefer that research (as matters now largely stand) be organised and supported primarily nationally? The upshot of the directive may be that national research is strengthened • Francis Crawley, BMJ 28 Feb 2004

44. What are the next steps?

45. Remember . . . • The EU has set itself the task of becoming the largest knowledge based economy in the world • 3% of GDP to be spent on research in line with US and Japan • EU has suggested industry match two thirds of total research spending (ie 2% of GDP)

46. Beware . . . • Neglecting clinical research in favour of basic science research • Failing to clearly and transparently define the relationship between industry, academia, and regulators • Destroying research capacity and innovation by making the process too bureaucratic

47. A thought from the Lancet • Cooperation with industry is valuable, and is important for advances in therapy and diagnosis. However, a balance needs to be re-established, and academia should uphold high scientific and ethical standards, and, if possible, impose them on industry

48. A final thought from the BMJ • There must, of course, be a balance between the needs of research and the interests of patients—but, as healthcare workers lack evidence for much of what they do, research is important. It is unlikely to be in the public interest to make it more difficult to do research