Clinical trials registry

A clinical trials registry is an official platform and catalog for registering a clinical trial. Some countries require clinical trials being conducted in that country to be registered, other do not require it, but often strongly encourage it. ClinicalTrials.gov, run by the United States National Library of Medicine (NLM) was the first online registry for clinical trials and is the largest and most widely used today.

Clinical trials are conducted to allow safety and efficacy data to be collected for health interventions (e.g., drugs, diagnostics, devices, therapy protocols). The goal of a clinical trials registry is to provide increased transparency and access to clinical trials, made available to the public. Clinical trials registries are often searchable (for example, trials can be searchable 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".[1]

Creation and development

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.[2] This worry has been international and written about for over 50 years.[3] 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.[4] 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.[5]

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 .

International participation

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][7] 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."[8][9]

The World Health Organization maintains an international registry portal at http://apps.who.int/trialsearch/.[10] 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."[11]

Since 2007, the International Committee of Medical Journal Editors ICMJE accepts all primary registries in the WHO network in addition to clinicaltrials.gov. The complete list is as follows:

Number of registered studies per registry

Worldwide, there is growing number of registries. A 2013 study[12] identified the following top five registries (numbers updated as of August 2013):

1. ClinicalTrials.gov 150,551
2. EU register 21,060
3. Japan registries trwork (JPRN) 12,728
4. ISRCTN 11,794
5. Australia and New Zealand (ANZCTR) 8,216

Clinical trial registries by country

Africa

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 Zealand

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).[13] The registry is in English.

Brazil

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).

Canada

The Canadian Institutes of Health Research (CIHR) participates with the ISRCTN.

China

China's clinical trial registry is called ChiCTR and its website is chictr.org. It is available both in Chinese (Mandarin) and English.

ChiCTR was established in October 2005, one week after India's registry was established and it participates in the World Health Organization’s International Clinical Trials Registry Platform.[14]

Cuba

Cuba's clinical registry is the RPCEC (Cuban Public Registry of Clinical Trials).[15]

Europe

Main article: EudraCT

EudraCT is a non-public database of all drug trials in the European Community (EC) from May 1, 2004 onwards. Its website is eudract.ema.europa.eu. In March 2011, EUCTR was launched, which is the public version of EudraCT including phase II to IV trials plus all pediatric trials.

Germany

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.[16]

India

India's clinical trials registry, CTRI, was established in October 2005 and registration became mandatory from 15 June 2009. Its website is .

CTRI is in English and it participates in the World Health Organization’s International Clinical Trials Registry Platform.[14]

Iran

Iran's registry, the IRCT, is available at irct.ir. It is run and funded by the Iranian Ministry of Health and Medical Education.[17]

Italy

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

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.[18] While the search portal is only available in Japanese, the three registries' sites are also available in English:

Netherlands

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

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.[19]

South Korea

South Korea's registry is Clinical Research Information Service (CRiS) and available at 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.[20]

Sri Lanka

The Sri Lanka Clinical Trials Registry (SLCTR) is available at slctr.lk. It is funded by the Sri Lanka Medical Association and managed by the Sri Lanka Clinical Trials Registry Committee.[21]

United Kingdom

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.

United States

Main article: clinicaltrials.gov

Clinical trials in the US are registered on clinicaltrials.gov.

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, CliicalTrials.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.[22]

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).

Other Registries

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.

ClinicalStudyResults is an online database of clinical trials maintainted by PhRMA, available at http://www.clinicalstudyresults.org/.

ClinicalTrialSearch.org is an open source semantic database of Clinical Trials, available at http://www.clinicaltrialsearch.org/.

Pharmaceutical industry initiative

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.

References

  1. ↑ http://www.who.int/ictrp/network/bpg/en/index.html
  2. ↑ Dickersin, K; Rennie, D (2009). "Registering clinical trials". JAMA. 290 (4): 516–523. doi:10.1001/jama.290.4.516. PMID 12876095.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ Dickersin, K; Rennie, D (2012). "The evolution of trial registries and their use to assess the clinical trial enterprise". JAMA. 307 (17): 186101864. doi:10.1001/jama.2012.4230. PMID 22550202.
  6. ↑ http://www.sanctr.gov.za/
  7. ↑ http://www.icmje.org/faq_clinical.html
  8. ↑ http://www.wma.net/en/30publications/10policies/b3/index.html
  9. ↑ http://www.anzctr.org.au/Default.aspx
  10. ↑ 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.
  11. ↑ http://www.who.int/ictrp/en/
  12. ↑ 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. PMID 23396544.
  13. ↑ http://www.anzctr.org.au/about.aspx
  14. 1 2 http://www.who.int/mediacentre/news/releases/2007/pr41/en/index.html
  15. ↑ http://www.who.int/ictrp/network/rpcec/en/index1.html
  16. ↑ http://www.who.int/ictrp/network/drks2/en/index.html
  17. ↑ http://www.who.int/ictrp/network/irct2/en/index.html
  18. ↑ http://www.who.int/ictrp/network/jprn2/en/index.html
  19. ↑ http://www.doh.gov.za/docs/index.html
  20. ↑ http://www.who.int/ictrp/network/cris2/en/index.html
  21. ↑ http://www.who.int/ictrp/network/slctr2/en/index.html
  22. ↑ 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. PMID 24687070.
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