I have, for years, complained about drug companies the FDA and the inherent, and dangerous, conflict of interest the industry-dominated approval board posed to the appropriate evaluation of clinical trials in, and subsequent approval of, medicine. Another area I've been concerned with is the publication bias of the studies used in evaluating medicine and the rampant "best-study forward" cheating in the industry.
In the area of "conflict of interest" the FDA routine allowed people with material ties to a drug to sit, and vote, on the advisory panel, claiming that to stop such practices would make it impossible to secure expert opinion. Well, despite the strenuous, and well coordinated, arguments from the apologists in industry and the overly-industry-compliant FDA,
last year the line of argumentation taken by the FDA was implicitly negated by the FDA's own
actions:The Food and Drug Administration said yesterday that it plans to make extensive changes in how it selects medical experts to serve on its advisory panels after years of complaints that many of them have financial ties to the companies whose products they evaluate.
...
In recent years, concern about the composition of the panels has reached a crescendo. The FDA and others have argued that overly strict rules might eliminate many -- in some cases all -- of the panel candidates with the needed expertise.
Yesterday, officials maintained that the agency's procedures have not been biased in favor of industry, but the new guidelines implicitly acknowledge what critics have long said -- that it is possible to find enough qualified experts who do not have ties to drug and device manufacturers.
The second area of concern I have is that drug companies submit studies of medications to the FDA for approval, unfortunately, they also have a long and dishonorable past of not submitting studies that are neutral to efficacy, or even contrary to efficacy. This cherry-picking of data can lead to toxic and dangerous drugs being prescribed that, frequently, have little or no benefit. Fortunately, in 2007 the Democratic lead Congress did manage to force more disclosure. However, it's not a panacea as drug companies, like the Bush administration, like to hide behind trade "secrets" to prevent full disclosure and the current regulations allow them to hide their problems:
Lack of access to data is an ongoing problem in the United States, despite passage of the Food and Drug Administration Amendments Act (FDAAA) of 2007, which was intended to make clinical trial data more transparent. The act requires most clinical trials to be registered and their results to be posted at ClinicalTrials.gov, a clinical trials registry of the National Library of Medicine. It’s an admirable first step, but the FDAAA may not reduce the likelihood of dangerous or ineffective drugs remaining on the market as much as some people might have hoped. For one thing, it fails to fully overcome the problem of publication bias, in part because some studies do not have to be registered or have their results posted (such as preclinical or toxicity trials or trials for drugs and devices that fail to win approval for any indication).
Well, at least they're incremental steps. And, over-time, we'll get some better science so we can make better decisions. But what about the past... Can we rely on the newer medicines approved under the old process? Maybe not:
Antidepressants
An untold story?
A recently published study analysing the effectiveness of some antidepressants highlights the ongoing problem of how study results may be distorted by failure to make data fully available. Jeanne Lenzer and Shannon Brownlee report
New generation antidepressants aren’t all they’re cracked up to be. That seems to be the central message in the meta-analysis published this week by Irving Kirsch and colleagues in PLoS Medicine, and it was this message that made the headlines. Kirsch’s conclusion follows on the heels of similar studies showing that statins are useful in only a small subset of patients taking the drugs2 and earlier studies finding that the safety and performance of cyclo-oxygenase-2 (COX 2) inhibitors were worse than they first seemed. All of which further reinforces previous criticisms that regulators in the United Kingdom and the United States are not doing their duty to protect the public from useless or dangerous drugs. But there’s another, deeper problem here—a problem that, ironically enough, was highlighted by GlaxoSmithKline’s news release stating that Kirsch’s conclusions are "incorrect" because he evaluated only a "small subset of the total data available." How can regulators, the public, and doctors know how useful (or how potentially dangerous) drugs really are unless outside researchers have access to all the data?
Trade secrets. What a load of crap. Except for a small amount of manufacturing data, when it comes to trade-secrets for data suppression, the exception should be absolutely abolished. I'm not interested in your bullshit press release when you considered clinical trial data, that ends up with people dead, a "trade secret." It's not. It's just data. You either fully disclose, or go to hell:
Perhaps the most daunting obstacle to full access to data—and one that the FDAAA doesn’t deal with—is the trade secrecy rules that allow the FDA and industry to prevent disclosure of critical data, regardless of what they are now required to post on ClinicalTrials.gov. This aspect of drug regulation surfaced in 2005, with the death of 19 year old Traci Johnson, who committed suicide while serving as a healthy volunteer in a trial of duloxetine for a new indication, urinary incontinence. After requesting the data on duloxetine from the FDA, one of us (Lenzer) found that Johnson’s death, in addition to those of at least four other volunteers, was not included. When questioned, the FDA cited trade secrecy laws, which permit companies to withhold all information, even deaths, about drugs that do not win approval for a new indication, even when the drug is already on the market for other indications.
People are more important than profits. At least in the minds of what I would considered to be "right-thinking" people. Libnuta and Dick Cheney's of the world be damned.
The full meta-analysis is
here. It is not exceptionally kind to the FDA or drug industry:
The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance.
When the sugar pills are as effective, for most patients, as the marginally-effective, if not ineffective, expensive drugs... And forty-million people are taking them because medical practitioners have been lead to believe these pills are "magical"... Of COURSE the manufacturer is going to deny everything, the profits are huge, and who cares if:
Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries, due to the small possibility of hepatic (liver) injury, which could lead to the need for a liver transplant, or even death.
The US Food and Drug Administration body (FDA) requires all antidepressants, including venlafaxine, to carry a black box with a generic warning about a possible suicide risk. In addition, the most recent research indicated that patients taking venlafaxine are at increased risk of suicide. A study conducted in Finland followed more than 15,000 patients for 3.4 years. Venlafaxine increased suicide risk 1.6-fold (statistically significant), as compared to no treatment. At the same time, fluoxetine (Prozac) halved the suicide risk.
With fluoxetine in addition to the less dangerous side-effects, rash or urticaria, sometimes serious, was observed in 7% patients in clinical trials; one-third of these cases resulted in discontinuation of the treatment. Postmarketing reports note several cases of complications developed in patients with rash. The symptoms included vasculitis and lupus-like syndrome. Death has been reported to occur in association with these systemic events.
December 2004 European Medicines Agency (EMEA), i.e. the Committee for Medicinal Products for Human Use (CHMP), informed patients, prescribers and parents that paroxetine should not be prescribed to children. CHMP gave a warning to prescribers recommending close monitoring of adult patients at high risk of suicidal behaviour and/or suicidal thoughts. In other words, CHMP does not prohibit use of paroxetine with adults but stresses extreme caution in actual usage. Also withdrawal reactions upon stopping treatment is mentioned and therefore it is recommended to gradually reduce the dose over several weeks or months if decision of withdrawal is made.
I don't deny these drugs have their uses. I do question the wide-spread prescription of them, however, when they have serious side-effects and there is question to whether they're any more effective for for most depressives than a placebo. I know for certain doctors will prescribe medicine to make their patients satisfied with the care they receive, even when it's not a bona-fide medical necessary.
Really, I'm an adult. Don't sugar coat it. Don't give me snake-oil cures that don't work. Don't hide the dangers, I can't make rational decisions with bad information.