Transparency in Clinical Data Reporting: from Coming Trends to New Demands

 

While evidence-based approach has been widely accepted as gold standard for health research and medical practice, growing concern has been raised about inadequate public reporting of clinical trial results. The following issues are in focus:

  • incomplete and inaccurate reporting
  • untimely disclosure of results
  • selective publication of positive findings

Failure to thoroughly describe the results and publish them in a timely fashion could potentially underlie important problems related to health economics:

  • provide biased estimates of treatment effects
  • lead to poor allocation of resources for research and health interventions
  • contribute to suboptimal regulatory and public health recommendations

Long-term adverse consequences arising from bad reporting ultimately hamper progress in medical research, impede optimal health care, and, finally, reduce public trust in the health care professions and evidence-based medicine itself.

Moreover, the fact that a proportion of clinical trial results never achieve a public domain gives rise to ethical problems with respect to participating volunteers, who risk their health without any benefit to medical science.

Call for openness

Efforts to increase transparency were reflected in a set of statements, legislative acts, directives, guidelines, and their later revisions and amendments.  

  • In 2007, the US Congress passed the Food and Drug Administration Amendments Act (FDAAA), which required posting basic clinical trial results to the clinicaltrials.gov database1.
  • In 2014, it became mandatory for sponsors of clinical trials registered with the EU Clinical Trials Register to post summary results in the European Clinical trials Database (EudraCT)2.

Both laws defined reporting timeframes of no longer than 1 year following the end of the trial.

Ethical imperative to make the main results publicly available was outlined in the latest version of the Declaration of Helsinki3 and the World Health Organization (WHO) Statement on Public Disclosure of Clinical Trial Results4 published in 2015.

At the same time, posting of clinical trial results in the corresponding registries was encouraged by the International Committee of Medical Journal Editors5. The need to improve quality of reporting in scientific literature was recognized by scientists and editors. Guidance for authors was developed in the form of the CONSORT (Consolidated Standards of Reporting Trials) statement6 (last extended and modified in 2010). The statement was endorsed by many medical journals and editorial organizations.

EMA’s policy to support clarity and openness in reporting

In October 2014, the European Medicines Agency (EMA) released its policy on publication of clinical data for medicinal products for human use7, which entered into force on 1 January 2015. This policy is applicable to clinical data submitted to the Agency under the centralized marketing authorization procedure.

According to this policy, the Agency publishes clinical reports (clinical overview, clinical summaries, and clinical study reports together with three appendices) within a certain time after the decision-making process on the application for authorization is complete. Information becomes available on EMA's clinical data website8. In a second phase, the Agency aims to publish both clinical reports and individual patient data.

Access to clinical data is provided by the following ways:

  • view-on-screen access (for general information purposes). Available for any registered user
  • expanded access to downloadable clinical reports (for academic and non-commercial research purposes). Available for identified users

By implementation of this policy, the Agency intends to facilitate trust and confidence in its decision-making processes. Furthermore, it believes that greater transparency will foster developing new knowledge in the interest of public health.

The main concerns related to the Agency’s initiative were related to:

  • protecting identity of clinical trial participants
  • protecting commercially confidential information (CCI)

In order to address these concerns, EMA obliged applicants to submit anonymized data along with the anonymization report, which describes the methods used to depersonalize patients’ data. Besides this, any CCI can be redacted prior publication on the condition that the applicant provides a proper justification.

New Clinical Trials Regulation: maximal transparency

Regulation (EU) No 536/2014 of the European Parliament and of the Council on clinical trials on medicinal products for human use9 is expected to come into application in 2018.

It assigns the EMA the task to create EU Portal and Database, which will contain all clinical trial-related information, including protocol, assessment and decision on trial conduct, etc. It is noteworthy that the scope of the Regulation will cover investigational medicinal products regardless of whether they have received a marketing authorization.

Until the Regulation enters into application, EMA’s clinical data website serves as the most open resource providing information on the results of clinical trials conducted throughout the European Union.

 

References

[1] Food and Drug Administration Amendments Act of 2007. Accessed 15 March 2018. https://www.gpo.gov/fdsys/pkg/PLAW-110publ85/pdf/PLAW-110publ85.pdf

[2] European Medicines Agency. Posting of clinical trial summary results in European Clinical Trials Database

(EudraCT) to become mandatory for sponsors as of 21 July 2014. Accessed 15 March 2018. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/06/news_detail_002127.jsp&mid=WC0b01ac058004d5c1

[3] World Medical Association. World Medical Association Declaration of Helsinki. JAMA. 2013;310:2191.
http://dx.doi.org/10.1001/jama.2013.281053

[4] WHO Statement on Public Disclosure of Clinical Trial Results. Accessed 15 March 2018. http://www.who.int/ictrp/results/reporting/en/

[5] International Committee of Medical Journal Editors. Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals—updated December 2014. Accessed 15 March 2018. http://www.icmje.org/recommendations/

[6] The CONSORT (Consolidated Standards of Reporting Trials) statement. Accessed 15 March 2018. http://www.consort-statement.org/consort-2010

[7] European Medicines Agency policy on publication of clinical data for medicinal products for human use. Accessed 15 March 2018. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2014/10/WC500174796.pdf

[8] European Medicines Agency clinical data website. Accessed 15 March 2018.
https://clinicaldata.ema.europa.eu/web/cdp/home

[9] Regulation (EU) No 536/2014 of the European Parliament and of the Council on clinical trials on medicinal products for human use. Accessed 15 March 2018.
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-1/reg_2014_536/reg_2014_536_en.pdf

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