Pharmalotby Ed Silverman08/12/2013Over the past three years, the AIDS Healthcare Foundation waged a losing battle against Truvada, which is sold by Gilead Sciences, for AIDS prevention. The Los Angeles-based advocacy group, which also provides medical care in clinics, very vocally fought FDA approval on the grounds that prevention will unintentionally lead to riskier sexual behavior and, subsequently, more HIV infections [back story].
Last week, though, AHF won a different kind of victory against the FDA. A federal judge ruled the agency improperly withheld Truvada safety and efficacy data in response to a Freedom of Information Act requested filed by the advocacy group two years ago. The FDA had argued the data did not have to be disclosed because Gilead trade secrets and confidential information would have been compromised. As a result, the agency must provide “complete and unredacted” copies of Truvada safety and efficacy records to AHF. In her ruling, US District Court Judge Margaret Morrow wrote that the FDA failed to prove that the documents that had been withheld were “confidential” financial and commercial records or that disclosure of data summaries and analyses would cause Gilead “substantial competitive injury.”
In reaching her conclusion, Morrow noted, for instance, that the agency made unsubstantiated arguments that Gilead faced competition in the market for AIDS prevention medicines and that releasing certain information, such as statistical methods and analyses applied to third-party data that was used to obtain FDA approval for Truvada, could potentially harm Gilead [GILD] at a later date. We should note that Morrow also decided that redacted correspondence was properly withheld since the information expressed incomplete agency views not reflected in the final labeling of the product [here is the ruling]. Of course, the initial issue that prompted AHF to seek the documents is no longer on the table – the FDA approved Truvada last year for AIDS prevention. But the advocacy group did manage to score points on a larger issue by successfully arguing against FDA efforts to make blanket determinations about releasing certain data and subsequent harm to drugmakers.
The AHF, however, suggested the ruling underscores concerns that the FDA and Gilead worked surreptitiously to ensure Truvada was approved. In particular, AHF seized on statements by David Pizzuti, vp of regulatory affairs at Gilead, that the FDA and drugmaker held tlks about Truvada trials results and data submissions needed for approval. “This ruling confirms one of our deepest suspicions: the FDA colluded with Gilead to fast-track approval of Truvada as PrEP regardless of the results of clinical trials. [The ruling] suggests the FDA advised Gilead how to conceal unfavorable clinical trial results and coached them on what to say to get those unfavorable results spun in such a way that the FDA deemed them sufficient to approve the drug,” AHF president Michael Weinstein said in a statement…
- Does it statistically separate from placebo? [p]
- How strong is the effect compared to placebo? [NNT, Odds Ratio, Effect Size]
- How does its effect strength compare to other efficacious drugs?
With adverse effects, hiding negative things is more difficult, but the stakes are so high that the drug companies have been relatively creative in pulling it off. But even the most honest reporting is only on short term studies [6-8 weeks], and many side effects are more insidious and take longer to develop. So things like the sexual side effects of Prozac or the weight gain with Zyprexa are minimized when the drug is released only to be discovered in their true glory later.
The drug companies don’t want to make the results of the Clinical Trials available for two reasons. The first is that their competitors will use the truth against them. For that, they have my sympathy but their past behavior has brought them to the present. The second reason is that right-thinking scientists will keep them honest about the risk/benefit ratio of their drugs. Given what has happened in psychiatry, that is now the only acceptable way forward.
“This ruling confirms one of our deepest suspicions: the FDA colluded with Gilead to fast-track approval of Truvada as PrEP regardless of the results of clinical trials. [The ruling] suggests the FDA advised Gilead how to conceal unfavorable clinical trial results and coached them on what to say to get those unfavorable results spun in such a way that the FDA deemed them sufficient to approve the drug,” AHF president Michael Weinstein said in a statement…”- David Pizzuti
Why is this happening?
“There are two types of laws in the U.S., each designed to constrain a different type of power: constitutional law, which places limitations on government, and regulatory law, which constrains corporations. Historically, these two areas have largely remained separate, but today each group has learned how to use the other’s laws to bypass their own restrictions. The government uses corporations to get around its limits, and corporations use the government to get around their limits.”
“The Public/Private Surveillance Partnership”
Bruce Schneier August 5, 2013
http://www.schneier.com/blog/archives/2013/08/the_publicpriva_1.html
Also:
Bayh–Dole Act:
https://en.wikipedia.org/wiki/Bayh-Dole_Act
The second argument against data transparency would be “patient confidentialty” yet:
http://www.businessweek.com/articles/2013-08-08/your-medical-records-are-for-sale
But improving medical care is NOT the only point. Making money is the ONLY point, and if medical care improves, well that’s just a fortunate side effect. It’s sad, but this is the world we have created for ourselves (and our patients).
a-non, you state: the FDA colluded with Gilead to fast-track approval of Truvada as PrEP regardless of the results of clinical trials.
Nothing new. I’ve contended for more than a decade that Eli Lilly drew the roadmap . . . and others have followed. When rDNA insulin was “in the pipeline”, it’s approval was iff-y, at best. Henry I. Miller, an early biotech drug advocate within the agency circumvented the approval process. While his boss, who was hesitant to push for the approval of human insulin, was out of town, Mr. Miller successfully lobbied his boss’ boss and gained approval for this genetically-engineered product. He effectively side-stepped the checks-and-balances in place within the organization, and bragged about his role in fast-tracking an unproven, dangerous, unnecessary drug.
Hopefully Goldacre’s AllTrials will expand to include a (long) look back. rDNA insulin was granted approval with the caveat that Phase IV (post marketing) data would be collected and analyzed. Twenty-five years late . . . and we still don’t see comparative analysis. Meanwhile, the number of insulin-dependent diabetics who have been harmed or killed by this dangerous drug remains unknowable. After all, patient non-compliance and “it’s just the disease” remain acceptable excuses for inaction by regulators.
Two decades ago the Federal Aviation Administration (FAA) had the dual charter or ensuring air travel safety while also promoting the business of air travel. The ValuJet crash into the Florida swamps changed all that, as the public perceived the low budget ValuJet was an accident waiting to happen. Could the FAA manage both mandates? Congress decided against it, changing the FAA’s charter to focus on solely on safety. The rationale was sound, there’s a potential conflict of interest in the two mandates in that FAA might be tempted to withhold publicizing safety issues due to the potential impact on air travel. There was no evidence of this, but it was a common sense solution as the potential existed.
Flash forward fifteen years; air travel has exploded to record levels, prices are relatively inexpensive, the FAA’s reputation is sterling, and safety has improved tremendously. The Asiana crash at SFO was the first major airliner crash in the US in eleven years. Customer service is terrible, but one can‘t blame that on the FAA. Regardless, the customers continue to come.
How is this situation any different from that at the FDA? Perhaps if drugs killed people 300 at time in spectacular fashion it might get some traction but I doubt it. Forty thousand from Vioxx over five years gets little attention despite the fact it’s equivalent to a 737 crashing every six days. Something is really wrong here, the FDA can’t both oversee and serve pharma.
Is there some reason why any company (or private citizen with a lab) could not get their hands on enough of a drug to figure out how it is made in order to reproduce it, then tweak it just a little like BigPharma typically does to make something “new” and “wow”?
IMO, FDA approval should be far more demanding, and what Jeff said. New drugs should be on probation for ten years while epidemiological studies are done at the drug companies’ expense by independent researchers. Patients should be fully informed about the status of drugs, and there should be public service messages educating people so that they have at least know that their are risks and benefits to be weighed and they are taking chances when they take any drug. Visual data would also help people understand odds, too.
FYI
“August 12, 2013, 2:53 pm
A Glut of Antidepressants
By RONI CARYN RABIN
Over the past two decades, the use of antidepressants has skyrocketed. One in 10 Americans now takes an antidepressant medication; among women in their 40s and 50s, the figure is one in four.
Experts have offered numerous reasons. Depression is common, and economic struggles have added to our stress and anxiety. Television ads promote antidepressants, and insurance plans usually cover them, even while limiting talk therapy. But a recent study suggests another explanation: that the condition is being overdiagnosed on a remarkable scale.
The study, published in April in the journal Psychotherapy and Psychosomatics, found that nearly two-thirds of a sample of more than 5,000 patients who had been given a diagnosis of depression within the previous 12 months did not meet the criteria for major depressive episode as described by the psychiatrists’ bible, the Diagnostic and Statistical Manual of Mental Disorders (or D.S.M.).
The study is not the first to find that patients frequently get “false positive” diagnoses for depression. Several earlier review studies have reported that diagnostic accuracy is low in general practice offices, in large part because serious depression is so rare in that setting.””
http://well.blogs.nytimes.com/2013/08/12/a-glut-of-antidepressants/?src=recg&pagewanted=print
http://www.youtube.com/watch?v=SvpkLvxsspg
genius at work.
Diagnosing depression is an inherently subjective task, said Dr. Jeffrey Lieberman, the president of the American Psychiatric Association.
“It would be great if we could do a blood test or a lab test or do an EKG,” Dr. Lieberman said, noting that similar claims of overtreatment have been made about syndromes like attention deficit hyperactivity disorder. “A diagnosis is made by symptoms and history and observation.”
In one consultation with a little checklist. There is no way out of being subjective when evaluating a patient’s depression, but the “objective” knowledge that it’s bio-bio-biological is a given. No implicit bias, confirmation bias, or financial incentive here, nope, nuh uh.
“The only secrets being protected are that the drug’s efficacy is marginal and that its toxicity has been minimized. Those are secrets worth revealing”
Well said.
Have you ever seen the Drug labeling information for lithium carbonate?
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=84d579dd-f12b-b727-6380-fd217ec115db
No Clinical Trial information at all, no information on icidence of side effects, and to top it all off, the drug was approved for a DSM-2 diangosis considered a DSM-3 equivalent.
This drugs approval was before psychiatry declared itself ‘evidence based’ in the DSM-3, and yet children receive it for ‘childhood bipolar disorder’ in perpetual as ‘Maintenance therapy”!
Another irony (if my history is correct):
Some of the changes in FDA regulation in the early 1990’s was a result of AIDS advocates trying to get drugs on to the market faster. While I understand thier motives, the change in regualtions in that era set the stage for the many problems that have developed over the past 20 years.