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Charting two years of collaborative progress in clinical trial data sharing.
Stakeholders across the life sciences industry agree that greater access to patient-level data is a good thing-good for science, good for business and good for humanity. Data sharing can generate valuable new insights or hypotheses for further research. Data sharing enables researchers to review clinical trial results to find insights and opportunities not identified by the original sponsors. Data sharing honors the valuable information provided by patients and researchers in previous clinical trials and extends the future value of their efforts.
But for all the benefits, there are caveats as well. Unless appropriate safeguards are in place, open access to clinical trial data could compromise patient privacy, enable faulty science, and be a resource-intensive burden for trial sponsors and data stewards.
If data sharing is to be truly valuable to researchers, it will require consensus among competitors on many issues of process and policy. What information should be shared, with whom and for what purposes? How should data access and use be managed? How far back in time should study data be made available? How do we ensure patient privacy without unduly limiting the research value of the data? How should outputs from this open access be managed? To make good on the promise of transparency, these questions would not be answered in isolation.
In October 2013, our organization brought together leaders from across
the global pharmaceutical industry to stimulate conversation on the best way to move forward, and to see what others were doing-or not-in sharing clinical trial data. That event became the first of a series to formalize and facilitate discussions that had been taking place in various corners of the industry and academia. The fifth forum, held in April 2015 in Heidelberg, Germany, brought together 142 delegates from 63 organizations in 13 countries to advance the data-sharing agenda in a truly collegial way.
Evolution in thinking
Until just a few years ago, discussions about sharing clinical trial data-particularly patient-level data with enough richness for secondary analysis-would have been framed in uncertainty and resistance. How much work is this going to be? What if we get flooded with data requests, or we can’t get our hands on the data? How can we balance the public good with the imperative for privacy? What happens if researchers reach different conclusions from our own-or reach false conclusions through bad science or malicious intent? Will we be scooped or scandalized by our own data?
These concerns, while real, can be mitigated by governance and stewardship. In the two years since convening the first industry forum, we have seen positive answers to those questions, leading to a notable shift in organizational culture and the tenor of the discussions:
That evolution in attitude in part reflects a growing appreciation for the benefits of transparency, but it also reflects a race against impending (and recently enacted) government regulation. The industry would rather define its own course than have one imposed.
Evolution in regulatory, industry expectations
The earliest push for data sharing came from the European Medicines Agency (EMA), which in 2012 committed to complete transparency regarding patient-level clinical data and study results. In 2014, the EMA announced that it would publish the clinical study reports contained in most all applications for marketing authorizations submitted after Jan. 1, 2015.
The pharmaceutical industry demonstrated further support for sharing clinical trial data in 2013 when the members of Pharmaceutical Research and Manufacturers of America (PhRMA) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) developed and endorsed Principles for Responsible Sharing of Clinical Trial Data.
The EMA led the way, but there has been a constellation of influences. For example:
This type of patient-level data sharing, particularly where there are multiple trial sponsors, was unfamiliar ground for the life sciences industry until just a few years ago. The status quo was one where clinical trials data was released very selectively-if at all-at the discretion of the trial sponsor, unless disclosure was required, such as by litigation or regulation.
Data sharing has officially moved from concept to reality. For example, as of September 2015, ClinicalStudyDataRequest.com had received 165 research proposals (including 16 multi-sponsor proposals) and provided data to hundreds of researchers to support 72 active research projects.
“We’re in an environment where expectations around data transparency are enormous,” said Andy Powrie-Smith, EFPIA’s communications director, at the Heidelberg forum. “We will create incredible amounts of data that we have to harness for the benefit of patients, to develop new therapies that save people’s lives. At the same time, there’s a lot of work to do getting internal policies and procedures in place to align with new regulations. There has been a perception that transparency is an on/off button. Press the button and you’re transparent. It clearly isn’t like that. It’s a process, a journey where there’s a lot of learning still to do.”
Data sharing: An academic’s perspective
Halfway through the learning curve, data sharing is imperfect in the real world. Just ask a researcher on the other end of the data-sharing equation. Take epilepsy research, for example.
For about 70 percent of patients with epilepsy, seizures can be controlled with drugs, but which one should be prescribed? Some of the more than 30 available medications will have adverse effects or not work for a given patient. Others will significantly improve quality of life. What factors determine which drugs will be best suited for which patient? Could a combination of direct and indirect evidence-triangulated across studies in comparative analysis -be used to better inform treatment choice?
That’s what Sarah Nolan wanted to know. The University of Liverpool researcher started with access to patient-level data from nearly 6,000 patients representing 29 existing studies-academic, pharmaceutical and government studies. The research team had requested and received data from another 18 studies (20% of that wave of requests could not be fulfilled because data from some older studies was not available in digital form).
There were still rich resources left to tap. Nolan identified 41 new studies representing more than 10,000 patients. She requested them all-24 academic studies, 16 pharmaceutical studies and one government study. After more than two years of data requesting, only five requests were successful. Nolan got only 8% of the total data requested, representing only 660 patients.
The other requests stalled for years. Nolan would sometimes get an initially positive response, but no data ever arrived. Other times, she got no response to her emails, and didn’t even know if her requests had reached the right person.
“The consequence of this is that the project was completely delayed, with only six months left in the research funds,” Nolan said. “The problem was a lack of transparency in the data requesting process. There wasn’t a clear point to go to actually request data.”
That was then. At the April 2015 forum, Nolan shared more recent experience using the ClinicalStudyDataRequest.com site. “In June 2013, a data inquiry was submitted for data, and a year later, June 2014, the data was provided to us in the SAS data access system for analysis. We also made three other inquiries that were unsuccessful in 2013 and 2014. It’s not ideal; we would have preferred to have that data, but at least we got a response and a reason.”
Nolan noted some usability challenges with the system, as well as constraints in data sharing agreements, and said her team is working with the sponsors to address these concerns and improve both the system and processes.
“A multi-sponsor environment is a brilliant time saver,” said Nolan. “You don’t have to submit the same documents again and again to different companies. The steps on the website are very clear, and the process allows a good level of communication between the data provider and the researcher. If all the companies have the same data structures and consistency in legal documents, that will save a lot of time.
“Having independent review panels is fair; they would see the science of the project above commercial self-interest. The process is detailed and encourages good science in the detail of your request. Legal documents have mutual benefit to the company and the researcher [because they specify rights to publish]. If I can’t publish this at the end with my name on it, I won’t get any more research money.”
Remembering the why
The trend toward clinical trial data transparency continues to gain momentum. But amid all the essential debate around how clinical data transparency can be achieved, it’s important we remember why we are doing it and what researchers need from us.
“Just because it’s online doesn’t mean it’s helpful,” said Karla Childers, director of strategic projects at Johnson & Johnson, at the April 2015 forum. “We shouldn’t measure the success of data sharing by how many proposals were received or approved, or how many terabytes of data shared.”
“There should be a value in terms of advancing science and public medicine,” added Childers. “We need to think creatively to ask the tougher questions. How are people using the systems? What has been the impact of sharing data? How can we tell it is working? Have treatment guidelines changed? Have we affected public health? What measures should we be capturing now to be able to answer those questions? As leaders in R&D, we need to be thinking about how we’re going to answer these questions.
“If we have improved public health, we’ve seen the value-if we can do this in a way that preserves innovation, protects patient privacy and protects confidential information. We have to move forward. There is no reverse on this.”
Patrick Homer is Industry Consultant and Matt Gross Director, both with the Health and Life Sciences Global Practice at SAS. They can be reached at firstname.lastname@example.org and email@example.com, respectively. Matt Gross is a member of Pharm Exec’s Editorial Advisory Board.