not their round…

Posted on Saturday 31 January 2015

When I open a medical journal and look at an article, there’s something called a by-line under the title that lists the authors of the article, usually with some little subscripts that lead to a footnote that lists the academic institutions they represent. Sometimes there’s one name. Sometimes it looks like a small army. But until a few years ago, I assumed that those were the people who wrote the article. And it’s also my assumption that the article wouldn’t have been published in a peer-reviewed journal if it wasn’t submitted as written by a peer.

Now, we’ve arrived at a point in time where the published results from a number of these articles are being questioned, and the broad consensus is that the raw data from these articles needs to be reanalyzed by independent investigators. It’s not just an academic interest that drives this call for reanalysis. It’s because these drugs remain in wide use based on the efficacy and safety results published in those articles – often certified by the FDA in the drug approval process.

And yet when we read about the process of making this data available in articles such as the one below, nowhere are the authors on that by-line mentioned, nor the academic institutions they represent, nor the peer-reviewed journals that published the original articles – nor, for that matter, do we hear about the clinical research centers where the studies were conducted, nor the clinical research organization that oversaw the studies, nor the medical writing  companies that wrote the articles. All we hear about are the sponsoring pharmaceutical companies we know collectively as PHARMA:
Pharmalot: WSJ
By Ed Silverman
Jan 29, 2015

With considerable fanfare, the Institute of Medicine released a long-awaited report last month praising the virtues of sharing clinical trial data. This is an important, but also contentious issue because without access to such information it can be virtually impossible for independent researchers to verify results that can lead to improved treatments, better health care and lower costs. Although the report is nothing more than a set of recommendations, the IOM effort is, nonetheless, seen as a needed step toward prodding industry and academia to release detailed data. Many drug makers, in particular, have been reluctant to grant much, if any, access over concerns about relinquishing trade secrets and compromising patient privacy, among other things. But some have taken steps to do so.

There is, however, one area where some experts say the report falls short and underscores ongoing difficulties in sharing trial information. While the IOM offers specific suggestions for releasing data from future trials, the institute did not provide a framework for obtaining retrospective data. This remains an unresolved issue for the pharmaceutical industry, especially in light of various safety scandals and ensuing litigation that revealed data for some products were never fully published or disclosed. “Clinical trials underpin the approval of medicines that are in use today, so if we don’t have access to that older data, how can we verify accuracy and conduct independent analyses?” says Peter Doshi, an assistant professor of pharmaceutical health services at the University of Maryland. “It’s a basic issue surrounding data transparency.”

One IOM committee member, Ida Sim, a professor at the University of California, San Francisco, says the report does suggest sharing retrospective data, but on a case-by-case basis and for studies that may influence clinical care. Why? Informed consent must be obtained from people who participated years earlier. Often, researchers have scattered. “We have to be pragmatic and realistic.”
I’ve made my argument about "informed consent" already [a special pleading]. But as to "researchers have scattered," I presume they’re talking about the authors on the by-line. In most cases, they weren’t really involved in the first place [speaking of being "pragmatic and realistic"]:
Some say convenience and liability are also factors. “Obviously, it’s less burdensome for companies to only have to do so going forward, especially if there’s a product on the market that’s raising concerns,” says Diana Zuckerman, who heads the National Center for Health Research, a non-profit think tank. “I see it as a way to protect companies from disclosing embarrassing and expensive information.”
The "burden" has been born already by doctors and patients who have been operating on questionable information. More to the current point, the burden "going forward" will be born by those in the future taking and prescribing these medications without more accurate efficacy and safety profiles. And speaking of "embarrassing," how do they think the prescribers now feel? And, by the way, who has born the "expense" of these medications in the past or "going forward?"
Murray Stewart, however, argues progress is being made. As chief medical officer at GlaxoSmithKline, he oversees an effort to disclose data going back 15 years and has convinced nine other drug makers to similarly provide access through a jointly run website. But most will not provide retrospective data. “We’ve shown it can be done,” he says. “But it’s a long journey” getting others on board. The inconsistent approaches underscore a key issue – finding a universal gatekeeper to vet researcher requests and corporate concerns. Harlan Krumholz, a Yale University cardiologist, is trying to offer a template with the Yale Open Data Access project, which last month signed an agreement with Johnson & Johnson to provide data for diagnostic and device products, but only as of 2014. A deal that J&J signed with YODA last year covers drugs and does not have a cut-off date for data requests. So far, J&J has not refused any request, but Krumholz says any J&J refusal would be disclosed on the site. “We are open science advocates,” he says, “and are not interested in giving anyone a pass.”

Meanwhile, some say the FDA has been a hindrance. While European regulators have a policy that allows researchers to make requests, the FDA does not. An FDA spokeswoman says the agency published a notice seeking comment about ways to make trial data available. But that was nearly two years ago. She says reactions are being evaluated and next steps are being considered. “I think FDA should make as much information available as possible, as soon as possible, particularly for approved drugs, including any safety information that might not be in the primary trials,” says Steve Goodman, a Stanford University School of Medicine professor. “What we need to avoid is the situation where the FDA is in possession of information that could materially impact or alter the assessment of the relative benefits and harms of a drug, and that is not easily available to other scientists or the public.” And “information they have on ‘failed’ drugs can often have an impact on marketed drugs or on other new drugs in the same class, so such information can be quite important as well, even though currently little or no information about such drugs can be divulged.”
The fact that the FDA has colluded with industry in the past in keeping data secret is really no real concern of ours. The only real question is when are they going to set up a mechanism to right this previous wrong? That they are set in their ways or don’t want to take the time isn’t really a consideration here. The damage done trumps their torpor.
    ra·tio·nal·ize   rash-na-liz
    verb

      : to think about or describe something [such as bad behavior] in a way that explains it and makes it seem proper, more attractive, etc.

All of these arguments are rationalizations that bear little relationship to any reality worth considering. PHARMA’s reasons for not wanting us to see what they did are obvious and immaterial. It’s time to stop arguing with them and get on with the business of getting what we need. This is not their round to win…

Afterthoughts: I left out something that should’ve been included. I’m on a team that has been granted access to the raw data from a "legacy" RCT by GSK. The annonymized data is well annonymized. The issue of requiring new consent forms never came up, and it shouldn’t have. There’s no personally identifying information present. My other afterthought is simple. If they don’t want to give us access to the old Clinical Trial Data, they can just repeat the studies with the proper consent forms, reasonable oversight, and subsequent Data Transparency. There’s ample evidence to justify insisting that contested RCT reports need to be reevaluated "going forward" no matter how it happens…

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