Sharing clinical trial results and other data, while a relatively new practice in the industry, is a valuable means to improve clinical research. Not only does making data available provide other clinical investigators with information to conduct future trials, it also provides academics with data for research papers and members of the public with key facts about the breakthroughs in clinical trials.
Regardless of the collective benefits of sharing data and results, reportage is also a legal requirement. The mechanisms, which recently have been put in place, are not yet sufficiently robust to guarantee compliance, but change is happening.
In this post, we address why sharing data and having the means to do so effectively is crucial.
There have been times in the clinical trial community when study results and other important data should have been shared and wasn’t. In 2006, for instance, researchers at Oxford University in the UK tested a candidate tuberculosis booster vaccine on monkeys ahead of a human trial of 2,800 babies in South Africa.
Inoculated monkeys died at the same rate as those exposed to TB without receiving the drug treatment. Yet, this data was not shared until after funding and permission for the human trial had been received, writes Daily Telegraph reporter Henry Bodkin.
While that particular population of monkeys was one among many tested populations, the results were not included and researchers reported success in their animal trials. Debate raged when the information came to light with many arguing the researchers unethical due to incomplete disclosure. Others considered the researchers’ actions understandable given that other studies on animals showed the drug’s efficacy.
The point to consider, regardless of which side you take in the above example, is that there is often a legal requirement to disclose all the data. Indeed, this is what U.S. Congress did in 2007, when it made reporting of trial results a legal requirement.
Regardless of the legal requirements, data on how many trial sponsors actually report results is worrying, says Holly Fernandez Lynch, assistant professor of medical ethics and assistant faculty director of online education in the Department of Medical Ethics and Health Policy at the University of Pennsylvania’s Perelman School of Medicine.
Lynch refers to a STAT News investigation showing that in 2017 trial sponsors reported just 72 percent of required results to ClinicalTrials.gov, the federal database. This was up actually a 14 percent increase from two years earlier. Of the 72 percent, however, 40 percent of the results were submitted after the legal deadline.
Part of the problem is the FDA has in the past been reluctant to issue fines for non-compliance with rules governing the sharing of results. But this is changing, writes biomedical research and policy reporter Sara Reardon. The FDA has proposed heavy fines — $10,000 a day — for pharmaceutical companies that do not submit clinical trial results to ClinicalTrials.gov.
Former U.S. Vice President Joe Biden called for naming and shaming of pharma companies that do not share trial results. This has delivered change, Ed Miseta at Clinical Leader writes, as Biden’s high-profile has raised the importance of the issue.
The Food and Drug Administration Amendments Act (FDAAA) TrialsTracker, a website that names and shames the worst offenders, has also added weight to the push for change. The tactic is obvious and effective, Miseta explains, especially when trials are investigating life-threatening diseases such as cancer. No company wants bad press in these situations.
In the absence of fines, Miseta argues, shaming may be the most effective solution as it will rouse the public, putting pressure on stakeholders who will enforce action by the pharma companies.
The TrialsTracker site is not without its critics. Bioethicist Jennifer Miller says there is ambiguity around interpretation of the law outlined in FDAAA. It’s uncertain whether the tracking tool can grasp the “complexities and ambiguities” of the Final Rule, which details why and how to submit results.
And, according to FDA spokesperson Lauren Smith Dyer, the agency is also not quite certain of the functioning of the tracking tool. Indeed, to ensure compliance with the FDAAA Final Rule, a great deal of public and private information needs to be reviewed. The best hope at the moment is for the agency to review compliance on a case-by-case basis.
Legalities aside, sharing results from trials is an essential component in the progress of clinical development. This is why platforms such as the Clinical Study Data Request (CSDR) initiative are so important, which requires that clinical trial data be posted, plus trial protocol and a statistical analysis plan — all in addition to summary results.
CSDR provides a platform to share trial data among academics, pharma companies and research funders, Jen O’Callaghan at Wellcome’s Open Research explains.
Indeed, Wellcome recently joined CSDR, alongside The Bill & Melinda Gates Foundation, Cancer Research UK and Medical Research Council.
Those interested in the results can seek data and metadata of listed trials. Researchers requesting data must complete an application form, which is reviewed by an independent panel to assess whether the request for data is based on a viable research plan from a responsible research team.
Using platforms such as CSDR provides researchers with benefits such as more easily locatable data that can be reused to maximize its value, O’Callaghan explains. Indeed, researchers can access and analyze data from multiple trials, which simplifies compliance with funder and journal mandates and expectations.
Without a cohesive plan to demand, authenticate and control the sharing of data, much will be lost.
While some member companies of organizations such as PhRMA in the US and BIO in the UK, which represent the interests of its pharma company members, have embraced the culture of data sharing, others haven’t, explains Margaret McCarthy, executive director of the Collaboration for Research Integrity and Transparency at Yale Law School.
The result is that the public remains at risk, she adds. When data isn’t shared, citizens and doctors — who are not researchers — have to seek information on clinical research developments from multiple secondary sources, much of which could be inaccurate.
Demand has increased for pharma companies to be more transparent about data and trial results, Jocelyn Kaiser at Science Mag writes. This has led to some companies sharing anonymized patient data from trials with certain approved researchers and websites.
The International Committee of Medical Journal Editors now asks authors to provide a data sharing plan, which may include patient data. While controversy abounds, especially because of patient data sharing, the clinical research community seems positive.
Johnson & Johnson, for example, provides a YODA platform that allows researchers to request and share data. And Roche also provides researchers with information after requests have been validated by an independent review body.
The Institute of Medicine of The National Academies released a consensus study report titled “Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risk.” In it, the institute’s authors argue that data from clinical trials should be made available in a timely manner for the public benefit.
What was noteworthy in their argument was the timeframe for reporting results. There should be a grace period to do so rather than immediately after the trial’s completion. They listed multiple reason for this, including:
Of course, before data can be shared it needs to be efficiently collected and accurately processed. ClinPlus Report provides submission-quality statistical table and listing authoring tools for tabulating and listing trial data, and creating complex statistical summary tables.
ClinPlus Data Management (CPDM) enables researchers to perform single or double-key entry, with verification completed concurrently with second key and status maintained at the variable level. The CPDM features enhance data entry operations and strengthen overall performance of data processing teams. It logs functions such as data entry and initialization actions, and changes to verified data, query resolution, security settings, data structure and SAS formats for easily compiled reports to meet audit trail requirements.
To ensure compliance with legal requirements as well as industry best practice, it is essential sponsors share results and data from trials. By doing so, patients and researchers can both benefit from a bigger body of knowledge, which will result in more successful trials and faster time to market. Packaging and reporting data in an accurate and accessible way is vital to sharing it effectively.
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