The European Medicines Agency has announced a public consultation on how its new transparency rules should be applied to the clinical trial database specified in the 2014 EU Clinical Trial Regulation. Stakeholders are invited to send their comments before 18 February 2015.
The European Clinical Trial Regulation aims to create an environment that is favourable to conducting clinical trials in the European Union (EU), with the highest standards of safety for participants. The Regulation ensures that the rules for conducting clinical trials are consistent throughout the EU. It also transforms the level of information publicly available for each clinical trial carried out in the EU by requiring transparency on the authorisation, conduct, and results of the trial. The Regulation will apply to clinical trials that are registered once the Regulation is in operation (not before 28 May 2016).
The US Institute of Medicine has published its report into transparency around clinical trial data. Somewhat behind policy developments in Europe on this topic, the US body first announced its intention to review the area in April 2014 and issued a discussion framework in January 2014.
In response to 23 public- and private-sector sponsors in the United States and abroad, the Institute of Medicine (IOM) assembled a committee to develop guiding principles and a practical framework for the responsible sharing of clinical trial data. In its report, Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risk, the committee concludes that sharing data is in the public interest, but a multi-stakeholder effort is needed to develop a culture, infrastructure, and policies that will foster responsible sharing—now and in the future.
Specific recommendations in the report include that:
- Data sharing plans are registered with the trial registration before the trial begins
- Summary results are published within a year of a trial’s end
- Full data sets from a clinical trial should be shared within 18 months of the trial’s end
- Data sharing initiatives should be overseen by independent panels of experts and the public, and should be as transparent as possible.
The AllTrials campaign welcomed the report, but commented that its recommendations could have been stronger if they had included clear pathways to implementation and calls for audits of compliance.
On 1 January 2015 the new EMA policy on publication of clinical data entered into force. Under this policy, the Agency proactively publishes the clinical reports submitted as part of marketing-authorisation applications for human medicines. Since 2010 the Agency has been releasing clinical-trial reports on request, under its access-to-documents policy.
The policy will apply to clinical reports contained in all marketing-authorisation applications submitted after that date. The reports will be released as soon as a decision on the application has been taken.
The Agency embarked on this process because it believes that the release of data is about establishing trust and confidence in the system, because it will allow the public to better understand the Agency’s decision-making. In addition, academics and researchers will be able to re-assess data sets. The publication of clinical reports will also help to avoid duplication of clinical trials, foster innovation and encourage development of new medicines.
The FDA has issued draft guidance on the informed consent process, and particularly the content and language of the informed consent sheet and related discussions. The changes under consideration can be found in in the July 26, 2011 Federal Register in an ANPRM titled “Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators.”
The draft covers all elements of informed consent, from the general required elements to the specific responsibilities of IRBs, investigators, sponsors and the FDA. It also addresses specific additional topics:
- Review of Patient Records
- Non-English Speaking Subjects
- Subjects with Low Literacy and Numeracy
- Physically Challenged Subjects
- Impaired Consent Capacity
- Children as Subjects
- Subject Participation in More Than One Clinical Investigation
- Suspension/Termination of a Study
- Data Retention upon the Withdrawal of Subjects
- Reporting Aggregate Results of the Clinical Investigation
However, the lobby group AllTrials has criticised the FDA for omitting any discussion of the anonymised sharing of patient data by sponsors, which it supports as part of its agenda for transparency and open research.
The FDA will welcome comments on this draft until September 15th, 2014.
The European Medicines Agency (EMA) has announced that it will launch a final round of targeted consultations with key stakeholders on its draft policy on proactive publication of and access to clinical-trial data at the beginning of May. This will give key stakeholders and the Agency the opportunity to address any outstanding issues before the final policy is presented to the EMA’s Management Board for endorsement in June 2014.
On April 14th, the Council of Ministers, representing the governments of member states of the European Union, formally approved a draft regulation aimed at facilitating and speeding up the authorisation procedure of clinical trials, following its agreement by the European Parliament in earlier in April.
This means that the regulation is now adopted. It will enter into force 20 days following its publication in the Official Journal of the European Union and apply six months after a EU portal for the submission of data on clinical trials and a EU database identifying each clinical trial have become fully functional (but not earlier than two years after the regulation’s publication).
The Regulation is expected to be published in the Official Journal early in May. This will begin an adoption/transition period that will last for just over over 5 years.
Novartis has announced additional steps to further its transparency around clinical trial data. Researchers can also now request access to patient level data on newly approved innovative medicines in 2014 through the ideaPoint portal.
Novartis has long supported data transparency and was the first company to publish positive and negative study results of its innovative medicines within one year of the study completion further enabling clinical research while protecting patient privacy.
To date, Novartis has registered 2,720 trials on ClinicalTrials.gov and published 559 trial results on the same site as well as 1,777 clinical study summaries (known as “redacted clinical study reports”).
The high-profile debate throughout Europe on clinical trial data transparency has been mirrored in the US, particularly within the Institute of Medicine.
In follow up to its October 2012 workshop, the IOM is conducting a consensus study to recommend guiding principles and a framework for the responsible sharing of clinical trial data. A discussion framework has been issued, outlining preliminary thoughts on guiding principles that underpin the responsible sharing of clinical trial data, defines key elements of data and data sharing activities, and describes a selected set of data sharing activities. One goal of this framework is to facilitate identification of the numerous complicated issues that the committee might need to take into account in the strategies and practical approaches to sharing of clinical trial data that will be recommended in the committee’s final report.
Comments may be submitted to the committee at either of two forthcoming public workshops, or via the committee’s project website. Comments will be most useful if submitted by March 24, 2014. The committee expects to release its final report with findings and recommendations on strategies and practical approaches to responsible data sharing in late 2014.
Johnson & Johnson has announced that its subsidiary, Janssen Research and Development, LLC, has entered into a novel agreement with Yale School of Medicine’s Open Data Access (YODA) Project that will extend its commitment to sharing clinical trials data to enhance public health and advance science and medicine. Under the agreement, YODA will serve as an independent body to review requests from investigators and physicians seeking access to anonymized clinical trials data from Janssen, and make final decisions on data sharing. This is the first time any company has collaborated with a completely independent third party to review and make decisions regarding every request for clinical data.
“Sharing anonymized data from clinical trials is critical to advance public health because it furthers our understanding of diseases, expands the base of knowledge needed to develop new treatments, and generates new insights and more complete evidence to enable better healthcare decisions for patients – all while protecting patient privacy and confidentiality,” said Joanne Waldstreicher, MD, Chief Medical Officer, Johnson & Johnson. “We are pleased to collaborate with YODA to ensure that each and every request for access to our pharmaceutical clinical data is reviewed objectively and independently. This represents a new standard for responsible, independent clinical data sharing.”
Writing on the Forbes website, former Pfizer president John LaMattina criticized Roche for issuing a press release stating that its developmental drug bitopertin was no better than placebo in treating negative symptoms of schizophrenia in two phase III clinical trials, while four further clinical trials are still in progress. While he found the degree of transparency noteworthy, LaMattina is concerned that the announcement could have an influence on patients, particularly in a case like this, where the studies relate to measuring moods and emotions.
In the piece, he quotes Dr. Steven W. Ryder, former head of Clinical Development at Pfizer, who added “Bias influencing both arms may dampen, augment or leave unchanged the difference between trial arms. One thing for sure: Roche will likely have to perform an analysis of data gathered before and after the announcement.”