Dissident AIDS Database

Politico-socio-economicoLobbyingHIV drugsFDA approval
How a New Policy Led to Seven Deadly Drugs
 WILLMAN DAVID
  "Seven drugs approved since 1993 have been withdrawn after reports of deaths and severe side effects. A two-year Los Angeles Times investigation has found that the FDA approved each of those drugs while disregarding danger signs or blunt warnings from its own specialists. Then, after receiving reports of significant harm to patients, the agency was slow to seek withdrawals. According to "adverse-event" reports filed with the FDA, the seven drugs were cited as suspects in 1,002 deaths. Because the deaths are reported by doctors, hospitals and others on a voluntary basis, the true number of fatalities could be far higher, according to epidemiologists. The seven drugs were not needed to save lives... In 1988, only 4% of new drugs introduced into the world market were approved first by the FDA. In 1998, the FDA's first-in-the-world approvals spiked to 66%. The drug companies' batting average in getting new drugs approved also climbed. By the end of the 1990s, the FDA was approving more than 80% of the industry's applications for new products, compared with about 60% at the beginning of the decade. The political pressure mounted, and the FDA began to bow. By 1991, agency officials told Congress they were making significant progress in speeding the approval process. The emboldened companies pushed for more... That same year a Democrat-controlled Congress approved and President Bush signed the Prescription Drug User Fee Act. It established goals that call for the FDA to review drugs within six months or a year; Elashoff and other FDA reviewers discern a powerful message. "People are aware that turning something down is going to cause problems with [officials] higher up in FDA, maybe more problems than it's worth," he said. Elashoff left the FDA four months ago. "Either you play games or you're going to be put off limits . . . a pariah," said Dr. John L. Gueriguian, a 19-year FDA medical officer... "The people in charge don't say, 'Should we approve this drug?' They say, 'Hey, how can we get this drug approved?' " Said Dr. Rudolph M. Widmark, who retired in 1997 after 11 years as a medical officer: "If you raise concern about a drug, it triggers a whole internal process that is difficult and painful. You have to defend why you are holding up the drug to your bosses... You cannot imagine how much pressure is put on the reviewer". Each new drug application is accompanied by voluminous medical data, enough at times to fill 1,000 or more phone books. The reviewers must master this material in less than six months or a year, while juggling other tasks. ...Gurston D. Turner, a veteran pharmacologist with the FDA's scientific investigations division who retired this year : "If you know you must have your report done by a certain date, you get something done. That's what they [top FDA officials] count, that's all they count..."  Dozens of officials interviewed by The Times made similar observations. "The pressure to meet deadlines is enormous," said Dr. Solomon Sobel, 65, director of the FDA's metabolic and endocrine drugs division throughout the 1990s. And the pressure is not merely to complete the reviews, he said. "The basic message is to approve." The perception of coziness with drug makers is perpetuated by potential conflicts of interest within the FDA's 18 advisory committees, the influential panels that recommend which drugs deserve approval or should remain on the market. The FDA allows some appointees to double as consultants or researchers for the same companies whose products they are evaluating on the public's behalf. Few doubt the $100-billion pharmaceutical industry's clout. Over the last decade, the drug companies have steered $44 million in contributions to the major political parties and to candidates for the White House and both houses of Congress. The FDA reviewers said they and their bosses fear that unless the new drugs are approved, companies will erupt and Congress will retaliate by refusing to renew the user fees. This would cripple FDA operations--and jeopardize jobs. The companies' money now covers about 50% of the FDA's costs for reviewing proposed drugs--and agency officials say that persuading Congress to renew the user fees into 2007 is now a top priority. Yet even if the user fees remain, the FDA is prohibited from spending the revenue for anything other than reviewing new drugs. So while the budget for pre-approval reviews has soared, the agency has gotten no similar increase of resources to evaluate the safety of the drugs after they are prescribed... the FDA has not withdrawn any drug due to a company's failure to complete a post-approval safety study. Officials conceded this week that they still do not know how often the studies are performed"
  Los Angeles Times, Wednesday, Dec. 20, 2000 2000
The trouble with nevirapine
 Brink Anthony
  Boehringer Ingelheim had a bit more trouble pushing past the medicines regulators in Canada than it did in the US and Europe. Its licensing application filed on 13 June 1996 had bombed. A second one was wallowing. The Therapeutic Products Programme of Health Canada, a division of the Health Protection Branch, couldn’t see any benefit. Only terrible toxicity. But the company wasn’t used to taking no for an answer... On 5 March 1998, a mob of Treatment Action Campaign types – the Treatment Information Project, an arm of British Colombia People with AIDS – gatecrashed a meeting attended by Health Minister Allan Rock at St Paul’s Hospital in Vancouver and began mouthing off that his drug regulators didn’t know what they were doing: they “do not understand how the drugs work”, unlike the US FDA which has a “superior understanding.” Not only stupid but too independent too – characterised, in the BCPWA’s report of the day’s fun, as “ineffective in coordinating its work both internally and internationally. Drug company representatives express enormous frustration that there is little consistency in the personnel [that Health Protection Branch] assigns to work on a given file... The trick being to file in the US first and later in the secondary markets to pressurise the latter’s regulatory authorities into conforming with the US, where just about any shit goes down – 80 per cent of all licence applications approved nowadays], restrictive regulatory provisions [slightly higher standards in Canada – drug regulators being edgy there in the wake of the thalidomide disaster, particularly bad in that country thanks to regulatory inertia and laxity at the time], and limited resources... On 22 April 1998 Rock got his next answer, confirming that a conditional approval regime was being implemented. Also that nevirapine had been approved elsewhere but not at home. The interesting bit was why: “…the review of the new drug submission for Viramune did not reveal any conclusive effects on clinical end points nor on surrogate marker end points to support the benefit of Viramune in treating patients with HIV disease [i.e. even the latter were too flimsy]. The efficacy of Viramune was not clinically significant when evaluated against internationally recognised standards of efficacy for drugs used in the treatment of HIV. There are, in addition, safety concerns associated with Viramune use in clinical trials. A condition was duly attached to the licence, being, that’s right, that Boehringer Ingelheim come back with some evidence of clinical efficacy... In the headlong rush to oblige the Germans, the Canadians hadn’t got around to writing the rules concerning the enforcement of such undertakings. Internal communications reveal the confusion: Chris Turner, Manager of the Continuing Assessment Division asked, “Who is responsible for following up the conditions? … We do not have the review staff at present to accept such an assignment…” Ann Sztuke-Fournier of the Advertising and Promotions Unit replied, “...The conditions are unknown to me and the regulatory impact as well…do we have a regulatory authority for these limitations? I am not aware of any formal commitment or agreement to conduct post-marketing surveillance for this drug or under what conditions this drug has been approved.”
  www.virusmyth.net/aids/data/abnvp.htm2002
Anti-HIV drugs and other "AIDS-related" treatments approved by the FDA through February 19 2002
 Rasnick David
  The site lists 14 drugs given accelerated approval by the FDA. With AIDS treatments, accelerated approval means a drug did not complete phase three clinical trials and its approval was based on surrogate lab markers (CD4 cell counts and "viral load" numbers) rather than on improved health or increased survival as compared to a similar group of people not taking the drug. The FDA¹s provision for accelerated drug approval requires the manufacturer to provide clinical data in follow up or the FDA can withdraw approval of the drug. Dr. David Rasnick reports that, to best of his knowledge, none of the anti-HIV drugs receiving accelerated approval in the 1990s was followed up with the clinical data required to justify continued use. Rasnick notes, however, that the post-approval clinical data provided to the FDA must be negative since these drugs now come with black box warning labels. The highest FDA warning given when severe, life-threatening, and fatal reactions to a drug have been documented.
  www.fda.gov/oashi/aids/stat_app.html2002