Themes

Prospective registration of clinical trials

What is this about?

Trial registration is the publication of information about the design, conduct, and administration of clinical trials and should be registered before enrollment of the first participant. The information should be published on a publicly-accessible website at no charge, managed by a nonprofit organization, freely available to anybody and searchable electronically. Registration aims to 1) improve the transparency of these trials and to 2) protect stakeholder interests – including the interests of the subjects, the investigators, peer scientists and society in general.

Why is this important?

Those responsible for conducting clinical trials sometimes fail in their ethical obligations towards subjects, sponsors, the scientific community and the general public by not publishing study outcomes in a timely manner. Some do not make results available at all[i]. Problems surrounding the reporting of research outcomes could lead to an erosion of trust in clinical trials. Subjects feel their contribution is not respected, harms are not adequately managed, and taxpayers feel their money is misspent. A failure to report all of the outcomes of research also slows the pace of scientific development. The regulatory policies demanding clinical trials’ registration in advance of the purposed beginning of the study aim to address and mitigate these problems.

The registration of all interventional trials is considered to be a scientific and ethical responsibility. The Declaration of Helsinki states that "Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject". The trials registration offers the following advantages: 1) ensure global access to scientific data; 2) prevent unnecessary duplications, informing about similar or identical trials and therefore saving public resources; 3) offer to patients the possibility of being recruited in an experimental study; 4) facilitate the identification of publication bias and selective reporting ; 5) allow investigators to increase the quality of research design; 6) support international scientific cooperation by enabling researchers and health care practitioners to identify trials in which they may have an interest; and 7) reduce the tendency to under-report negative findings.(1)

Trial registers allow researchers to stay up to date on developments in their field, find collaborators, and identify research gaps. They are important for patients, their family members and caregivers, and health professionals to search for studies that are actively recruiting so they can participate or learn about new interventions and treatments being considered. They are important for journal editors and reviewers because they provide the context for understanding research results. By understanding the research context, they can identify publication bias and if the data was handled inappropriately.

[i] See e.g. Ross 2012, Chen 2016

For whom is this important?

Principal investigators, Researchers, Health care professionals, Supervisors, Journal editors

What are the best practices?

In 2004, the International Committee of Medical Journal Editors (ICMJE) announced that clinical trials beginning after July 1, 2005, would be under a new trial registration policy (2). To be published in member journals, the trials would have to be registered in an approved trial registry prior to the enrollment of the first participant. Since 2005, ICMJE has reiterated that registering a prospective study should be a condition of publication and after the announcement, several journals endorsed this policy. The registration must occur prior to enrollment of the first study participant in a trial registry that meets the quality criteria developed by WHO (3). However, the adherence for this requirement remains low by both researchers and journal editors and, unfortunately, not all clinical trials are registered before they start.

Recent findings suggest that among the reasons that lead to the low adherence to the new requirement by the researchers are: lack of awareness of the criteria; misunderstandings regarding the definition of clinical trial by ICMJE; and difficulties for registration (4). On the part of journal editors, the main reason is that not all journals are equally committed to meeting the registration requirements, strengths, and limitations of the study. The Committee on Publication Ethics suggested that “it is probably best to judge each paper on a case by case basis.”

Other information

References

1. WHO Statement on Public Disclosure of Clinical Trial Results. 2017. Available from:

https://www.who.int/ictrp/trial_reg/en/. Accessed May 2019.

2. International Committee of Medical Journal Editors. Clinical Trial Registration. Available from: www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html Accessed May 2019.

3. WHO Statement on Public Disclosure of Clinical Trial Results. 2017. Available from: https://www.who.int/ictrp/en/ Accessed May 2019.

4. Loder E, Loder S, Cook S. Characteristics and publication fate of unregistered and retrospectively registered clinical trials submitted to The BMJ over 4 years. BMJ Open2018;8:e020037. doi:10.1136/bmjopen-2017-020037



Anna Catharina Armond, Jonathan Lewis contributed to this theme.

Latest contribution was June 24, 2019