Clinical Trial Registration

1. Clinical Trial Registration ศ.พญ. พรรณแข มไหสวริยะ ผู้อำนวยการศูนย์ส่งเสริมจริยธรรมการวิจัยในคน มหาวิทยาลัยมหิดล

2. Agenda for today • What is clinical trial registration • Which type of clinical trails need registration • Benefit from clinical trial registration • What will happen if I do not register my trial • How to register a clinical trial

3. What is clinical trial registration • An official platform and catalog for registering a clinical trial • Clinical Trials.gov, run by the United States National Library Of Medicine (NLM) is the first online registry and is the largest and most widely used.

4. International Corporation • WHO – International Clinical Trials Registry Platform • the International Registry's Mission • "is to ensure that a complete view of research is accessible to all those involved in health care decision making • will improve research transparency • will ultimately strengthen the validity and value of the scientific evidence base."

5. International Corporation • The International Committee of Medical Journal Editors (ICMJE) decided that from July 1, 2005 no trials will be considered for publication unless they are included on a clinical trials registry

6. History of ICMJE • A small group of editors of general medical journals met informally in Vancouver, British Columbia, in 1978 to establish guidelines for the format of manuscripts submitted to their journals. This group became known as the Vancouver Group. • Its requirements for manuscripts, including formats for bibliographic references developed by the National Library of Medicine (NLM), were first published in 1979.

7. History of ICMJE • The Vancouver Group expanded and evolved into the International Committee of Medical Journal Editors (ICMJE), which meets annually. • The ICMJE has gradually broadened its concerns to include ethical principles related to publication in biomedical journals.

8. Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors. N Engl J Med 2004: 351;12. • Catherine De Angelis, M.D., M.P.H. JAMA • Jeffrey M. Drazen, M.D. New England Journal of Medicine • Prof. Frank A. Frizelle, M.B., Ch.B., M.Med.Sc.,F.R.A.C.S. The New Zealand Medical Journal • John Hoey, M.D. CMAJ • Richard Horton, F.R.C.P. The Lancet • Sheldon Kotzin, M.L.S. Executive Editor, MEDLINE National Library of Medicine • Christine Laine, M.D., M.P.H. Annals of Internal Medicine

9. Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors. N Engl J Med 2004: 351;12. • Charlotte Haug, M.D., Ph.D., M.Sc. Norwegian Medical Journal • Ana Marusic, M.D.Ph.D. Croatian Medical Journal • A. John P.M. Overbeke, M.D., Ph.D. Nederlands Tijdschrift voor GeneeskundeDutch Journal of Medicine • Torben V. Schroeder, M.D., D.M.Sc. Journal of the Danish Medical Association • Hal C. Sox, M.D. Annals of Internal Medicine • Martin B. Van Der Weyden, M.D. The Medical Journal of Australia

10. Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors. N Engl J Med 2004: 351;12. • Honest reporting begins with revealing the existence of all clinical studies, even those that reflect unfavorably on a research sponsor’s product. • Researchers (and journal editors) are generally most enthusiastic about the publication of trials that show either a large effect of a new treatment (positive trials) or equivalence of two approaches to treatment (non-inferiority trials).

11. Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors. N Engl J Med 2004: 351;12. • Researchers (and journals) typically are less excited about trials that show that a new treatment is inferior to standard treatment (negative trials) and even less interested in trials that are neither clearly positive nor clearly negative, since inconclusive trials will not in themselves change practice.

12. Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors.N Engl J Med 2004: 351;12. • Irrespective of their scientific interest, trial results that place financial interests at risk are particularly likely to remain unpublished and hidden from public view. • If all trials are registered in a public repository at their inception, every trial’s existence is part of the public record and the many stakeholders in clinical research can explore the full range of clinical evidence.

13. When did the policy apply? • Any clinical trial starting enrollment after July 1, 2005. • For trials that began enrollment before this date, the ICMJE member journals will require registration by September 13, 2005, before considering the trial for publication.

14. Which type of clinical trial required registration? • Any research project that • prospectively assigns human subjects to intervention or comparison groups • To study the cause-and-effect relationship between a medical intervention and a health outcome • Studies designed for other purposes, such as to study pharmacokinetics or major toxicity (e.g., phase 1 trials), would be exempt

15. Interventions include but are not restricted to • Drugs, cells and other biological products, • Surgical procedures, • Radiologic procedures, • Devices, • Behavioral treatments, • Process-of-care changes, • Preventive care, etc. This definition includes Phase 2 to 4 trials.

16. A registry should meets several criteria • The registry must be accessible to the public at no charge • Must be open to all prospective registrants and managed by a not-for-profit organization • There must be a mechanism to ensure the validity of the registration data • The registry should be electronically searchable

17. An acceptable registry must include at minimum the following information: • a unique identifying number, • a statement of the intervention (or interventions) and comparison (or comparisons) studied, • a statement of the study hypothesis, • Definitions of the primary and secondary outcome measures, • Eligibility criteria,

18. Minimal information required • Key trial dates • registration date, • anticipated or actual start date, • anticipated or actual date of last follow-up, • planned or actual date of closure to data entry, • date trial data considered complete

19. Minimal information required • Target number of subjects, • Funding source, • Contact information for the principal investigator.

20. ICMJE Recommendation • Journals publish the trial registration number at the end of the abstract • Whenever a registration number is available, authors list this number the first time they use a trial acronym to refer to either the trial they are reporting or to other trials that they mention in the manuscript.

21. the U.S. Food and Drug Administration Amendments Act of 2007 (FDAAA) • Requires researchers to register results • The ICMJE will not consider results to be previous publication if they are posted in the same primary clinical trial registry as the initial registration

22. Attention • To meet WHO requirements for transparency and publication, it is only necessary for your trial to be registered once, in either • a Primary Registry in the WHO Registry Network or • an ICMJE approved registry.

23. International Corporation • Declaration of Helsinki Oct 2008 – Item 19. Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject

25. Agenda for today • What is clinical trial registration • Which type of clinical trails need registration • Benefit from clinical trial registration • What will happen if I do not register my trial • How to register a clinical trial

26. Why is Trial Registration Important? The registration of all interventional trials is considered to be a scientific, ethical and moral responsibility because: • to ensure that decisions about health care are informed by all of the available evidence • It is difficult to make informed decisions if publication bias and selective reportingare present

27. Why is Trial Registration Important? • Describing clinical trials in progress can make it easier to identify gaps in clinical trials research • Making researchers and potential participants aware of recruiting trials may facilitate recruitment • ClinicalTrials.gov requires registration update within 30 days of a change to any of the following: • Recruitment status • Completion date The record verification date should be updated at least every 6 months for studied that are not yet completed, even if there were no change to the record

28. Why is Trial Registration Important? • Improving awareness of similar or identical trials will make it possible for researchers and funding agencies to avoid unnecessary duplication • Enabling researchers and health care practitioners to identify trials in which they may have an interest could result in more effective collaboration among researchers. The type of collaboration may include prospective meta-analysis

29. Why is Trial Registration Important? • Registries checking data as part of the registration process may lead to improvements in the quality of clinical trials by making it possible to identify potential problems (such as problematic randomization methods) early in the research process

30. Require by law!

32. Agenda for today • What is clinical trial registration • Which type of clinical trails need registration • Benefit from clinical trial registration • What will happen if I do not register my trial • How to register a clinical trial Next speaker