The Swiss National Clinical Trials Portal a new database on clinical trials?

Transcription

1 The Swiss National Clinical Trials Portal a new database on clinical trials? Meet and Greet for Swiss Biomedical Librarians 8 September 2014, Hotel Kreuz, Berne Hosted by the Biomedical Library Committee of the Swiss Academy of Medical Sciences Andri Christen, PhD Epidemiologist Human Research and Ethics Federal Office of Public Health, Switzerland

2 Content Why do we need registries for clinical trials? - The problem and the solution The history of clinical trial registries - International and national registration policies The Swiss way to clinical trials registration - Specific requirements: What, where, when, and by whom? - Registration process The Swiss National Clinical Trials Portal (SNCTP) - Today and tomorrow 2

3 Let s talk clinical trials Clinical trials deliver the (pen-) ultimate piece of evidence on the effect of health related interventions They follow strict scientific standards protecting participants and guaranteeing reliable study results Art. 3 Definitions (Human Research Act, HRA) l. Clinical trial means research project in which persons are prospectively assigned to a health-related intervention in order to investigate its effects on health or on the structure and function of the human body. Art. 2 Definitions (Ordinance on Clinical Trials, OClin) a. Health-related intervention: Procedure on/with persons in preventive, diagnostc, therapeutic, palliative, or rehabilitative regard. 3

4 Who relies on (reliable) clinical trial results? Investigators and systematic reviewers Experts to create medical guidelines Education Clinicians practicing evidence-based medicine Competent regulatory authorities approving new therapies Health insurances and regulators deciding, which therapy to remunarate Legislators The general public to understand regulatory decisions (cf Tamiflu scandal) and last but not least patients to make informed decisions 4

5 The problem Publication bias - distorted evidence due to selective publication of research results - Overreporting of positive results (Rochon et al. 1994; Tramèr et al. 1997; Von Elm et al. 2004) - Underreporting of negative results (Hopewell et al. 2009) - Selective publishing and modifying of outcomes (Hahn et al. 2002; Chan et al. 2004; Turner et al. 2008; Vedula et al. 2009; Dwan et al. 2008). - Duration to publication (Stern and Simes 1997; Dickersin et al. 2002; Hopewell et al. 2007; Prayle et al. 2012) - Publication language (Egger et al. 1997; Juni et al. 2002) - Probability to be cited (Gøtzsche 1987; Ravnskov 1992; Ravnskov 1995; Kjaergaard and Gluud 2002; Schmidt and Gøtzsche 2005; Nieminen et al. 2007) 5

6 The extent of the problem 6

7 The extent of the problem 7

8 The consequences of the problem Oseltamivir (Tamiflu): Trials with 60% of pa1ent data not reported Full study reports inaccessible for 29% of trials Rosiglitazone (Avandia): à Billions of dollars spent worldwide (US$3 3 billion in 2009 alone) to stockpile a drug that did not necessarily Unfavourable reduce trials hospital and sponsor s admissions meta- analysis and pulmonary not reported complica1ons in pa1ents with pandemic Increased influenza, risk and of that myocardial had unclear infarc1on harms. confirmed by independent meta- analysis of 56 rosiglitazone trials, which included 36 unreported trials for which data were obtained from the sponsor s trial registry à addi1onal myocardial infarc1ons in pa1ents taking rosiglitazone in the USA and UK in

9 The solution to the problem: Full transparency Four levels of transparency measures: 1. Prospective registration of clinical trials in public registries to reveal the existence of all trials, published or not ( birth certificate ); 2. Registration of main trial s results after completion, and publication and discussion of results in peer-reviewed journals; 3. Access to full details about the trial s methods and results in clinical study reports; 4. Sharing participant-level data. 9

10 History of clinical trials registration policies 10

11 Federal Department of Home Affairs FDHA Soft-law policies (2005) The ICMJE member journals will require, as a condition of consideration for publication in their journals, registration in a public trials registry. (2008) 19. Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject. 11

12 What to register The WHO Registry Network (ICTRP) provides prospective trial registries with a forum to exchange information and work together to establish best practice for clinical trial registration. 12

13 WHO Trial Registration Data Set (Version 1.2.1) 1/ 2/ 3: Trial identification and registration information 4: Source of funding 5/ 6: Information on sponsor (responsible party for conducting the trial) 7/ 8: Contact information for public and scientific queries 9: Public title 10: Scientific title 11: Countries of recruitment 12: Health condition/problem studied 13: Intervention evaluated 14: In- and exclusion criteria 15: Study type 16: Date of first enrollment 17: Target sample size 18: Recruitment status 19/ 20: Primary and secondary outcomes 13

14 Califf RM et al. JAMA. 2012;307(17):

15 Characteristics of clinical trials in Switzerland Maurer R. 4. Forum Patientennahe klinische Forschung, Freiburg i.b Studies submiwed to ethics commiwee (ZH) in 2011/12: 61% of submiwed studies are non- drug trials 32% are industry sponsored trials 15

16 Is the academic research community ready for more transparency? Results: Only 282/1299 (22%) PIs par1cipated in survey. Only 31% willing to publicly disclose study protocol and financial agreements. à Future discussions on trial registra1on should not only focus on industry sponsored but also on academic ini1ated research Scherer M. & Trelle S. BMC Health Services Research 2008, 8:18; doi: /

17 The Swiss way to clinical trials registration Motion Hubmann 2005: More transparency in clinical trials Requirement to register clinical trials in a public registry by law Response from federal council: Motion to be addressed in the new law on human research 17

18 Art. 1 Purpose 1 The purpose of this Act is to protect the dignity, privacy and health of human beings involved in research. 2 It is also designed to: a. create favourable conditions for research involving human beings; b. help to ensure the quality of research involving human beings; c. ensure the transparency of research involving human beings. 18

19 Public registration of clinical trials by law Art. 56 Registration 1 Authorised clinical trials must be recorded in a public registry. The Federal Council may specify exemptions from mandatory registration; in doing so, it shall be guided by recognised international regulations. 2 It shall designate the registry, provide information on access thereto and specify the content thereof, as well as notification requirements and the notification procedure. In doing so, it shall have regard to recognised international regulations and if possible take existing registries into consideration. 3 It may: a. entrust public- or private-law organisations with the establishment and management of the registry; b. specify that the results of registered research projects are to be published in such registries. 19

20 Swiss specific requirements to register clinical trials: What, where and by whom? Ø Sponsor must register approved trials in: - A WHO primary registry; or - clinicaltrials.gov Ø Specific trial information must be made publicly available in national language in the database of the federal council 20

21 WHO primary registries and clinicaltrials.gov Australian New Zealand Clinical Trials Registry (ANZCTR) Brazilian Clinical Trials Registry (ReBec) Chinese Clinical Trial Registry (ChiCTR) Clinical Research Information Service (CRiS), Republic of Korea Clinical Trials Registry - India (CTRI) Cuban Public Registry of Clinical Trials(RPCEC) EU Clinical Trials Register (EU-CTR) German Clinical Trials Register (DRKS) Iranian Registry of Clinical Trials (IRCT) ISRCTN.org Japan Primary Registries Network (JPRN) Thai Clinical Trials Registry (TCTR) The Netherlands National Trial Register (NTR) Pan African Clinical Trial Registry (PACTR) Sri Lanka Clinical Trials Registry (SLCTR) + clinicaltrials.gov 21

22 Swiss specific requirements to register clinical trials: What? Ø Before start of clinical trial (any action of patient recruitement) Ø WHO Trial Registration Data Set (Version 1.2.1) Ø National language: Title, lay summary, intervention, investigated health condition, in- and exclusion criteria Ø Data from latest version approved by ethics committee 22

23 Swiss specific requirements to register clinical trials: Access to information? Ø Web-based portal contains public available information on clinical trials in Switzerland (ICTRP search function) Ø Portal merges ICTRP-database and database of the federal council on clinical trials conducted in Switzerland 23

24 Registries Registry Federal Department of Home Affairs FDHA WHO primary registries clinicaltrials.gov Studienportal.non-ch Registrierfunktionen Suchfunktionen Clinicaltrialsportal.gov Registrierfunktionen Suchfunktionen register Database of the federal council search Swiss National Clinical Trials Portal review Applicant (Sponsor/Investigator) Clinical trial submission Search Authorities (Ethics Committees) inform Public 24

25 Clinical Trials search SNCTP (Swiss Na1onal Clinical Trials Portal) Interested public 1. Search term Search field 2. Results Merged results Search Database with Info in na1onal language ICTRP- search service ICTRP- database 25

26 Swiss National Clinical Trials Portal - SNCTP 26

27 The future SNCTP 27

28 Relevance of registries for systematic reviews and meta-analysis 28

29 Take home message(s) Prospective clinical trial registration in a WHO-primary registry is indisputable Clinical trial registries must be searched besides recognised medical literature databases for conducting systematic reviews and meta-analysis SNCTP is not a new relevant database for the scientific community... but increases transparency for the general public... but mandatory registration of all clinical trials provides the base for more transparency in clinical research in Switzerland in general 29

30 Dr Marie-Charlotte Bouësseau, Team Leader of Ethics and Health Unit, WHO 30