Clinical trial registration
Clinical trial registration is the practice of documenting clinical trials before they are performed in a clinical trials registry so as to combat publication bias and selective reporting. Registration of clinical trials is required in some countries and is increasingly being standardized. Some top medical journals will only publish the results of trials that have been pre-registered.
A clinical trials registry is a platform which catalogs registered clinical trials. ClinicalTrials.gov, run by the United States National Library of Medicine (NLM) was the first online registry for clinical trials, and remains the largest and most widely used. In addition to combating bias, clinical trial registries serve to increase transparency and access to clinical trials for the public. Clinical trials registries are often searchable (e.g. by disease/indication, drug, location, etc.). Trials are registered by the pharmaceutical, biotech or medical device company (Sponsor) or by the hospital or foundation which is sponsoring the study, or by another organization, such as a contract research organization (CRO) which is running the study.
There has been a push from governments and international organizations, especially since 2005, to make clinical trial information more widely available and to standardize registries and processes of registering. The World Health Organization is working toward "achieving consensus on both the minimal and the optimal operating standards for trial registration".
Creation and developmentEdit
For many years, scientists and others have worried about reporting biases such that negative or null results from initiated clinical trials may be less likely to be published than positive results, thus skewing the literature and our understanding of how well interventions work. This worry has been international and written about for over 50 years. One of the proposals to address this potential bias was a comprehensive register of initiated clinical trials that would inform the public which trials had been started. Ethical issues were those that seemed to interest the public most, as trialists (including those with potential commercial gain) benefited from those who enrolled in trials, but were not required to “give back,” telling the public what they had learned.
Those who were particularly concerned by the double standard were systematic reviewers, those who summarize what is known from clinical trials. If the literature is skewed, then the results of a systematic review are also likely to be skewed, possibly favoring the test intervention when in fact the accumulated data do not show this, if all data were made public.
ClinicalTrials.gov was originally developed largely as a result of breast cancer consumer lobbying, which led to authorizing language in the FDA Modernization Act of 1997 (Food and Drug Administration Modernization Act of 1997. Pub L No. 105-115, §113 Stat 2296), but the law provided neither funding nor a mechanism of enforcement. In addition, the law required that ClinicalTrials.gov only include trials of serious and life-threatening diseases.
Then, two events occurred in 2004 that increased public awareness of the problems of reporting bias. First, the then-New York State Attorney General Eliot Spitzer sued GlaxoSmithKline (GSK) because they had failed to reveal results from trials showing that certain antidepressants might be harmful.
Shortly thereafter, the International Committee of Medical Journal Editors (ICMJE) announced that their journals would not publish reports of trials unless they had been registered. The ICMJE action was probably the most important motivator for trial registration, as investigators wanted to reserve the possibility that they could publish their results in prestigious journals, should they want to.
In 2007, the Food and Drug Administration Amendments Act of 2007 (FDAAA) clarified the requirements for registration and also set penalties for non-compliance (Public Law 110-85. The Food and Drug Administration Amendments Act of 2007 .
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. The World Health Organization has begun the push for clinical trial registration with the initiation of the International Clinical Trials Registry Platform. There has also been action from the pharmaceutical industry, which released plans to make clinical trial data more transparent and publicly available. Released in October 2008, the revised Declaration of Helsinki, states that "Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject."
The World Health Organization maintains an international registry portal at http://apps.who.int/trialsearch/. WHO states that 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. This will improve research transparency and will ultimately strengthen the validity and value of the scientific evidence base."
Since 2007, the International Committee of Medical Journal Editors ICMJE accepts all primary registries in the WHO network in addition to clinicaltrials.gov.
Number of registered studies per registryEdit
Worldwide, there is growing number of registries. A 2013 study identified the following top five registries (numbers updated as of August 2013):
|3.||Japan registries network (JPRN)||12,728|
|5.||Australia and New Zealand (ANZCTR)||8,216|
The Pan-African clinical trials registry (PACTR) is available at pactr.org. It is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) and operates out of the South African Cochrane Centre (Cochrane Collaboration) based at the South African Medical Research Council. PACTR's remit ensures that it can register all clinical trials that are conducted on the continent in all disease areas. PACTR is a primary member of the WHO's International Clinical Trials Registry Platform (ICTRP), and thus contributes data to the central search portal hosted by ICTRP.
Australia and New ZealandEdit
The countries of Australia and New Zealand share a registry. The ANZCTR is located at: anzctr.org.au.
Registering trials with the ANZCTR is voluntary. It is publicly owned and managed by a non-profit organization and is funded by an enabling grant from Australia's National Health and Medical Research Council (NHMRC). The registry is in English.
Brazil has a registry (the Registro Brasileiro de Ensaios Clínicos, abbreviated ReBEC) at: ensaiosclinicos.gov.br. ReBEC is a project of the Brazilian Ministry of Health, The Panamerican Health Organization (PAHO) and The Oswaldo Cruz Foundation (FIOCRUZ).
The Canadian Institutes of Health Research (CIHR) participates with the ISRCTN.
Cuba's clinical registry is the RPCEC (Cuban Public Registry of Clinical Trials).
EudraCT is a database of all clinical trials conducted in the European Union from 1 May 2004 onward. Initially a non-public database, it was launched for the public as EU Clinical Trials Register in March 2011.
Germany's clinical trials registry, the DRKS, is available at www.drks.de. The DRKS is an open access, free of charge online register for clinical trials and is available both in English and German. DRKS is part of the ICTRP network at WHO. The DRKS works with two partner registries in Germany, DeReG - German Registry for Somatic Gene-Transfer Trials and Clinical Trial Registry of the University Medical Center Freiburg.
India's clinical trials registry, CTRI, was established in October 2005 and registration became mandatory from 15 June 2009. Its website is .
Italy's The Portal of the Clinical Research with Medicines of the Italian Medicines Agency (AIFA) is a public source of information about the clinical trials with medicines conducted in Italy, the regulations and the ethical principles ruling the research, as well as the initiatives that AIFA promotes in the field of research. Unfortunately the portal has not been working since January 2013, for technical reasons; although it was expected to restart soon, an operational date has not yet been posted so far (July 2013).
Japan has three registries that work as a network known as the Japan Primary Registries Network (JPRN). Its search portal is hosted by the Japanese National Institute of Public Health. While the search portal is only available in Japanese, the three registries' sites are also available in English:
- University Hospital Medical Information Network (UMIN CTR)
- Japan Pharmaceutical Information Center - Clinical Trials Information (JapicCTI)
- Japan Medical Association - Center for Clinical Trials (JMACCT CTR)
The Netherlands registry participates with WHO and its website is trialregister.nl. While the "About" sections of the website are only available in the Dutch language, clinical trial data are available in English.
South Africa’s Department of Health announced in November 2005, that clinical trials conducted in the country must be submitted to the South African National Clinical Trials Register. Its site is located at: sanctr.gov. Clinical trial guidelines for South Africa are available at the Department of Health's official site.
South Korea's registry is Clinical Research Information Service (CRiS) and available at https://web.archive.org/web/20101121001837/http://ncrc.cdc.go.kr/cris/index.jsp. It is managed by the Korea Centers for Disease Control and Prevention and funded by South Korea's Ministry of Health and Welfare.
The ISRCTN registry was launched in 2000. Originally ISRCTN stood for 'International Standard Randomised Controlled Trial Number'; however, the scope of the registry has now widened beyond randomized controlled trials to include any study designed to assess the efficacy of health interventions in a human population. It registers both observational and interventional trials and content is curated by a team of expert editors.
This section needs to be updated. In particular: Add information about HHS making public more information about clinical trials (see link). (September 2016)
Clinicaltrials.gov is the largest clinical trials registry. Clinical trials conducted in the United States are required to be registered in the registry. As of January 2, 2015, ClinicalTrials.gov lists 181,612 studies with locations in 50 US states and in 187 countries. Its registrations represent about 75% of what is available through the WHO Portal (ICTRP). Despite the fact that important progress has been made, the efforts of those overseeing ClinicalTrials.gov and the other, smaller, registries do not ensure that the public has an unbiased knowledge base accessible to all. For example, problems of the concordance between the ClinicalTrials.gov record and the published record have been identified for many protocol and results items.
The registry traces back to the Health Omnibus Programs Extension Act of 1988 (HOPE or Public Law 100-607) which mandated the development of a database of AIDS Clinical Trials Information System. It would later be expanded under the Food and Drug Modernization Act of 1997 (FDAMA or Public Act 105-115). The registry is run by the United States National Library of Medicine (NLM).
Clinical trial registries are also set up and managed by governmental organizations, non-governmental organizations, universities, as well as commercial and nonprofit entities. This includes pharmaceutical companies, international organizations, and health organizations. A list is available at http://www.circare.org/registries.htm.
Pharmaceutical industry initiativeEdit
The IFPMA Clinical Trials Portal is a major pharmaceutical industry initiative designed to increase the transparency of clinical trials by providing a convenient "one-stop-shop" for published clinical trial information. It helps to fulfill the commitment made by the research-based pharmaceutical industry in its Joint Position on the Disclosure of Clinical Trial Information via Clinical Trial Registries and Databases. It is available here.
- "International Clinical Trials Registry Platform (ICTRP)". Who.int. Retrieved 2017-06-23.
- "WHO | Working Group on Best Practice for Clinical Trials Registers (BPG)". Who.int. Retrieved 2017-06-23.
- Barrett, Stephen. "Major Journals Press for Clinical Trial Registration". www.quackwatch.org. Retrieved 22 May 2019.
- "WHO - Working Group on Best Practice for Clinical Trials Registers (BPG)". www.who.int.
- Dickersin, K; Rennie, D (2009). "Registering clinical trials". JAMA. 290 (4): 516–523. doi:10.1001/jama.290.4.516. PMID 12876095.
- Sterling, TD (1959). "Publication decisions and their possible effects on inferences drawn from tests of significances – or vice versa". J Am Stat Assoc. 54 (285): 30–34. doi:10.1080/01621459.1959.10501497. JSTOR 2282137.
- International Collaborative Group on Clinical Trial Registries (1993). "Position paper and consensus recommendations on clinical trial registries. Ad Hoc Working Party of the International Collaborative Group on Clinical Trials Registries". Clin Trials Metaanal. 28 (4–5): 255–266. PMID 10146333.
- Dickersin, K; Rennie, D (2012). "The evolution of trial registries and their use to assess the clinical trial enterprise". JAMA. 307 (17): 1861–4. doi:10.1001/jama.2012.4230. PMID 22550202.
- SANCTR. "SANCTR > Home". www.sanctr.gov.za.
- "Archived copy". Archived from the original on 2010-07-06. Retrieved 2010-07-23.CS1 maint: Archived copy as title (link)
- "Archived copy". Archived from the original on 2011-08-30. Retrieved 2010-09-02.CS1 maint: Archived copy as title (link)
- "ANZCTR". www.anzctr.org.au.
- Gülmezoglu, AM; Pang, T; Horton, R; Dickersin, K (2005). "WHO facilitates international collaboration in setting standards for clinical trial registration". Lancet. 365 (9474): 1829–1831. doi:10.1016/s0140-6736(05)66589-0. PMID 15924966.
- "International Clinical Trials Registry Platform (ICTRP)". World Health Organization.
- Huser, V.; Cimino, J. J. (2013). "Evaluating adherence to the International Committee of Medical Journal Editors' policy of mandatory, timely clinical trial registration". Journal of the American Medical Informatics Association. 20 (e1): e169–74. doi:10.1136/amiajnl-2012-001501. PMC 3715364. PMID 23396544.
- "ANZCTR". www.anzctr.org.au.
- "WHO - China and India join WHO clinical trial registry platform". www.who.int.
- "WHO - RPCEC (Cuban Public Registry of Clinical Trials)". www.who.int.
- "WHO - German Clinical Trials Register (GermanCTR)". www.who.int.
- "WHO - Iranian Registry of Clinical Trials (IRCT)". www.who.int.
- "WHO - Japan Primary Registries Network (JPRN)". www.who.int.
- "Archived copy". Archived from the original on 2010-07-24. Retrieved 2010-07-23.CS1 maint: Archived copy as title (link)
- "WHO - Clinical Research Information Service (CRiS), Republic of Korea". www.who.int.
- "WHO - Sri Lanka Clinical Trials Registry (SLCTR)". www.who.int.
- Hartung, DM; Zarin, DA; Guise, JM; McDonagh, M; Paynter, R; Helfand, M (2014). "Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications". Ann Intern Med. 160 (7): 477–483. doi:10.7326/m13-0480. PMC 4617780. PMID 24687070.