Ed Silverman, Contributing Editor03.07.14
After a rancorous debate that has frayed the seemingly monolithic posture of the pharma industry and raised fundamental issues about transparency, Johnson & Johnson recently struck a noteworthy deal with a group of Yale University researchers to make clinical trial data available for scrutiny.
The move is potentially quite significant. By forging a go-it-alone path, the healthcare giant won points by leapfrogging its rivals, some of which have agreed — in varying degrees — to provide trial data for review and replication. Most drugmakers continue to remain silent about the issue.
“This is an extraordinary donation to society, and a reversal of the industry’s traditional tendency to treat data as an asset that would lose value if exposed to public scrutiny,” wrote Harlan Krumholz, M.D., who heads the Yale Open Data Access project, in an editorial in The New York Times. “. . . This is a breakthrough that should be replicated throughout the research world.”
Whether that happens remains to be seen. In general, the pharma industry argues that releasing patient-level data may compromise patient privacy, undermine trust in the regulatory system, increase the risk data would be misinterpreted and weaken incentives for research.
This last point refers to concerns that confidential commercial information would be handed to rivals, an issue that last year prompted two drugmakers — AbbVie and InterMune — to take the European Medicines Agency to court to prevent the release of trial data.
Meanwhile, two industry trade groups have harshly criticized an EMA proposal to proactively make data available once a decision has been made to approve a medicine. The protests by the Pharmaceutical Research & Manufacturers of America ( PhRMA ) and the European Federation of Pharmaceutical Industries Associations ( EFPIA ) have so far succeeded in forcing the agency to delay its final decision.
Nonetheless, a Solution is long overdue given that various safety scandals, as well as product-liability litigation, have revealed data for some drugs that was never fully disclosed or published. Such concerns, for instance, figured prominently in the wrenching debates over the safety of the Vioxx painkiller and Avandia diabetes Pill , among others medicines.
These points have been raised repeatedly by AllTrials, an online campaign devoted to pressuring drugmakers into greater disclosure. The effort has been backed by BMJ, the British Medical Journal, which will no longer publish studies unless anonymized patient-level data is made available.
All of which points to the fact that timing is crucial. The ability of researchers to independently verify safety and Efficacy results speaks not only to industry credibility but may also make it possible to improve patient treatments, which can Lead to improved health and lower costs. This is particularly important as cash-strapped governments look for ways to end the upward spiral of healthcare expenses.
Interestingly, the J&J deal establishes the YODA project as the type of gatekeeper that some view as a means of overcoming industry concerns. Recently, a group of academics and consultants, some of whom are affiliated with the Multi-Regional Clinical Trials Center at Harvard University, proposed an independent board to find a way through the disclosure thicket.
Essentially, the idea is to have a disinterested arbiter — or learned intermediary, as the MRCT Center calls it — to sort out researcher requests and industry objections. And this where the YODA project comes in: YODA will require proposals to identify researchers, funding and any conflicts, and also sign agreements that restrict them to the research question that is proposed.
“Most important, they must agree to share whatever they find. And we exclude applicants who seek data for commercial or legal purposes,” Dr. Krumholz wrote in his op-ed. “Our intent is not to be tough gatekeepers, but to ensure that the data are used in a transparent way and contribute to overall scientific knowledge.”
“The medical scientific community and population at large want to have more transparency on what we do,” J&J chief scientific officer and worldwide pharmaceuticals chairman Paul Stoffels told The Wall Street Journal. “To get really credible, we took the leap” to set up an independent way to make sure people get access to the data.
Why YODA? The Yale project undertook one attempt that yielded a significant outcome. Three years ago, YODA reached a deal with Medtronic to release all the data on a device that stimulates bone production of bone. Questions had been raised about safety and conflicts of interests involving some researchers.
After dismal publicity over the episode, a new Medtronic chief executive officer agreed to release trial data for independent review, which YODA subsequently analyzed and published. One study found the device was no better than a bone graft, and might be associated with a slight increase in cancer, while the other found that the device was effective and the cancer risk inconclusive. The effort was hailed as an overdue example of how an independent body can sort out complicated and sensitive issues in an unbiased and credible fashion.
As a result, the decision by J&J to work with YODA also exposes what has been a fundamental weakness in an effort undertaken by GlaxoSmithKline, which launched its own initiative to disclose trial data last year after reaching an embarrassing $3 billion deal with U.S. authorities for bad behavior that included a failure to release Avandia trial data.
Unlike the J&J effort, the GSK program allows the drugmaker to hold sway over the procedure for approving data requests. GSK maintains its panel is independent and will essentially function like a Data Safety Monitoring Board, which reviews trial data for safety and effectiveness. But the drugmaker decides on the composition of its panel. Pfizer will do the same with its own panel. And both contain people who have worked as consultants for the drugmakers.
There are other limitations. For instance, Pfizer recently expanded its disclosure policy and created a website that will publish synopses of clinical study reports filed with regulatory agencies for approved medicines for which basic results are posted in ClinicalTrials.gov. However, these only date to September 2007. In other words, the effort is incomplete.
Similarly, Sanofi will make available trial data and related documents, including clinical study reports, for studies in humans that were submitted to the FDA and EMA and the product must have been approved by both agencies — on or after January 1, 2014. Again, the disclosure is incomplete.
Meanwhile, GSK is already being put to the test by a group of researchers who are squabbling with the drug maker over its reluctance to release certain trial data for its Paxil antidepressant, a tiff that has drawn the attention of the New York State Attorney General, which had required GSK to make certain Paxil data available as part of settlement a decade ago.
GSK, by the way, was the first drugmaker to respond to the controversy by vowing to make data available. And several others have since formally joined its initiative, including Roche, Sanofi, Boehringer Ingelheim and ViiV Healthcare, which is a joint venture between GSK, Pfizer and Shionogi in HIV/AIDS medicines.
The moves reflect a deepening realization in the pharma industry that battling regulators and researchers over access is likely to further erode trust and could result in still more regulation.
In fact, at a recent conference on trial data disclosure issues at the Harvard University School of Public Health, Hans Eichler, a senior medical officer at the EMA, remarked, “What we’ve learned from people in other industries, such as people who drill holes in the Gulf of Mexico, is that the more trust there is for their products, the more leeway they have with regulation.”
Will other drugmakers emulate J&J? Or will they join GSK? Or will some drugmakers remain on the sidelines and further encourage their trade groups to resist disclosure? These are crucial questions and the responses will be worth watching.
For now, the YODA project may well offer the best chance at improving transparency and replicating questionable results.
Drugmakers that dismiss the effort, however, do so at their own peril. The veracity of their products and reputations are at stake. Dr. Eichler is correct. Trust is a very valuable asset.
Ed Silverman
Contributing Editor
Ed Silverman is a prize-winning journalist who has covered the pharmaceutical industry for The Star-Ledger of New Jersey, one of the nation’s largest daily newspapers, for more than 12 years. Prior to joining The Star-Ledger, Ed spent six years at New York Newsday and previously worked at Investor’s Business Daily. Ed blogs about the drug industry at Pharmalot, at www.pharmalot.com. He can be reached at ed.silverman@comcast.net.
The move is potentially quite significant. By forging a go-it-alone path, the healthcare giant won points by leapfrogging its rivals, some of which have agreed — in varying degrees — to provide trial data for review and replication. Most drugmakers continue to remain silent about the issue.
“This is an extraordinary donation to society, and a reversal of the industry’s traditional tendency to treat data as an asset that would lose value if exposed to public scrutiny,” wrote Harlan Krumholz, M.D., who heads the Yale Open Data Access project, in an editorial in The New York Times. “. . . This is a breakthrough that should be replicated throughout the research world.”
Whether that happens remains to be seen. In general, the pharma industry argues that releasing patient-level data may compromise patient privacy, undermine trust in the regulatory system, increase the risk data would be misinterpreted and weaken incentives for research.
This last point refers to concerns that confidential commercial information would be handed to rivals, an issue that last year prompted two drugmakers — AbbVie and InterMune — to take the European Medicines Agency to court to prevent the release of trial data.
Meanwhile, two industry trade groups have harshly criticized an EMA proposal to proactively make data available once a decision has been made to approve a medicine. The protests by the Pharmaceutical Research & Manufacturers of America ( PhRMA ) and the European Federation of Pharmaceutical Industries Associations ( EFPIA ) have so far succeeded in forcing the agency to delay its final decision.
Nonetheless, a Solution is long overdue given that various safety scandals, as well as product-liability litigation, have revealed data for some drugs that was never fully disclosed or published. Such concerns, for instance, figured prominently in the wrenching debates over the safety of the Vioxx painkiller and Avandia diabetes Pill , among others medicines.
These points have been raised repeatedly by AllTrials, an online campaign devoted to pressuring drugmakers into greater disclosure. The effort has been backed by BMJ, the British Medical Journal, which will no longer publish studies unless anonymized patient-level data is made available.
All of which points to the fact that timing is crucial. The ability of researchers to independently verify safety and Efficacy results speaks not only to industry credibility but may also make it possible to improve patient treatments, which can Lead to improved health and lower costs. This is particularly important as cash-strapped governments look for ways to end the upward spiral of healthcare expenses.
Interestingly, the J&J deal establishes the YODA project as the type of gatekeeper that some view as a means of overcoming industry concerns. Recently, a group of academics and consultants, some of whom are affiliated with the Multi-Regional Clinical Trials Center at Harvard University, proposed an independent board to find a way through the disclosure thicket.
Essentially, the idea is to have a disinterested arbiter — or learned intermediary, as the MRCT Center calls it — to sort out researcher requests and industry objections. And this where the YODA project comes in: YODA will require proposals to identify researchers, funding and any conflicts, and also sign agreements that restrict them to the research question that is proposed.
“Most important, they must agree to share whatever they find. And we exclude applicants who seek data for commercial or legal purposes,” Dr. Krumholz wrote in his op-ed. “Our intent is not to be tough gatekeepers, but to ensure that the data are used in a transparent way and contribute to overall scientific knowledge.”
“The medical scientific community and population at large want to have more transparency on what we do,” J&J chief scientific officer and worldwide pharmaceuticals chairman Paul Stoffels told The Wall Street Journal. “To get really credible, we took the leap” to set up an independent way to make sure people get access to the data.
Why YODA? The Yale project undertook one attempt that yielded a significant outcome. Three years ago, YODA reached a deal with Medtronic to release all the data on a device that stimulates bone production of bone. Questions had been raised about safety and conflicts of interests involving some researchers.
After dismal publicity over the episode, a new Medtronic chief executive officer agreed to release trial data for independent review, which YODA subsequently analyzed and published. One study found the device was no better than a bone graft, and might be associated with a slight increase in cancer, while the other found that the device was effective and the cancer risk inconclusive. The effort was hailed as an overdue example of how an independent body can sort out complicated and sensitive issues in an unbiased and credible fashion.
As a result, the decision by J&J to work with YODA also exposes what has been a fundamental weakness in an effort undertaken by GlaxoSmithKline, which launched its own initiative to disclose trial data last year after reaching an embarrassing $3 billion deal with U.S. authorities for bad behavior that included a failure to release Avandia trial data.
Unlike the J&J effort, the GSK program allows the drugmaker to hold sway over the procedure for approving data requests. GSK maintains its panel is independent and will essentially function like a Data Safety Monitoring Board, which reviews trial data for safety and effectiveness. But the drugmaker decides on the composition of its panel. Pfizer will do the same with its own panel. And both contain people who have worked as consultants for the drugmakers.
There are other limitations. For instance, Pfizer recently expanded its disclosure policy and created a website that will publish synopses of clinical study reports filed with regulatory agencies for approved medicines for which basic results are posted in ClinicalTrials.gov. However, these only date to September 2007. In other words, the effort is incomplete.
Similarly, Sanofi will make available trial data and related documents, including clinical study reports, for studies in humans that were submitted to the FDA and EMA and the product must have been approved by both agencies — on or after January 1, 2014. Again, the disclosure is incomplete.
Meanwhile, GSK is already being put to the test by a group of researchers who are squabbling with the drug maker over its reluctance to release certain trial data for its Paxil antidepressant, a tiff that has drawn the attention of the New York State Attorney General, which had required GSK to make certain Paxil data available as part of settlement a decade ago.
GSK, by the way, was the first drugmaker to respond to the controversy by vowing to make data available. And several others have since formally joined its initiative, including Roche, Sanofi, Boehringer Ingelheim and ViiV Healthcare, which is a joint venture between GSK, Pfizer and Shionogi in HIV/AIDS medicines.
The moves reflect a deepening realization in the pharma industry that battling regulators and researchers over access is likely to further erode trust and could result in still more regulation.
In fact, at a recent conference on trial data disclosure issues at the Harvard University School of Public Health, Hans Eichler, a senior medical officer at the EMA, remarked, “What we’ve learned from people in other industries, such as people who drill holes in the Gulf of Mexico, is that the more trust there is for their products, the more leeway they have with regulation.”
Will other drugmakers emulate J&J? Or will they join GSK? Or will some drugmakers remain on the sidelines and further encourage their trade groups to resist disclosure? These are crucial questions and the responses will be worth watching.
For now, the YODA project may well offer the best chance at improving transparency and replicating questionable results.
Drugmakers that dismiss the effort, however, do so at their own peril. The veracity of their products and reputations are at stake. Dr. Eichler is correct. Trust is a very valuable asset.
Ed Silverman
Contributing Editor
Ed Silverman is a prize-winning journalist who has covered the pharmaceutical industry for The Star-Ledger of New Jersey, one of the nation’s largest daily newspapers, for more than 12 years. Prior to joining The Star-Ledger, Ed spent six years at New York Newsday and previously worked at Investor’s Business Daily. Ed blogs about the drug industry at Pharmalot, at www.pharmalot.com. He can be reached at ed.silverman@comcast.net.
