by Jeanne LenzerBritish Medical Journal. 2016 355:i6098Manufacturers have told the US Food and Drug Administration [FDA] that restricting their ability to engage in “truthful and non-misleading speech” about off-label uses of drugs and devices infringes their rights to free speech. The comments were made during hearings held in Washington, DC, on 9 and 10 of November on whether to allow manufacturers to promote drugs and medical devices for uses not approved by the FDA. Public comment on the proposal to loosen off-label promotion is open until 9 January 2017. One in every five prescriptions in the US is estimated to be for off-label use. For example, the use of certain antibiotics in children, which have been tested and approved in adults, is one commonly accepted off-label use. But manufacturers are generally prohibited from promoting off-label use, with the exception of “safe harbor” activities, such as distributing reprints of peer reviewed journal articles that may discuss unapproved uses. Industry has sued the FDA in some cases where the FDA sought to limit their off-label activities and has scored some successes in court.
Approximately 60 speakers addressed the FDA. Robert Califf, commissioner of the FDA, opened the hearings by saying that the agency had historically restricted off-label promotion to ensure the efficacy and safety of vaccines, biologics, animal and human drugs, and medical devices. He said that some off-label promotions had had “devastating consequences.” As an example, he cited the case of atypical antipsychotic drugs, which were approved for the treatment of schizophrenia and bipolar disorder, but which some companies promoted to treat dementia and behavioral problems in elderly people “using tactics that obscured the absence of reliable evidence.” He said that “subsequent clinical trials showed an increased incidence of death” among elderly people when used in this off-label manner. Califf left the door open to the need for expanded off-label promotion, however, when he said that an “evidence gap” existed for information that was not available on a product label and that additional information might help healthcare providers make better decisions for patients.
About two dozen industry representatives, surrogates, insurers, and patient groups, including Pharmaceutical Research and Manufacturers of America, the Biotechnology Innovation Organization, and the Advanced Medical Technology Association, presented after Califf. They said that discussions between industry and healthcare providers, as well as payers, about emerging uses of drugs or devices not approved by the FDA were necessary for providers to plan formularies and fee schedules, to gain information about rapid developments in medicine that do not appear on product labels, and for doctors to learn about treatments for rare conditions for which randomized controlled trials were not feasible.
Advocates of off-label promotion said that the FDA needed to loosen the levels of evidence necessary to conduct discussions with healthcare providers. John Kamp, executive director of the Coalition for Healthcare Communication, said that manufacturers should not have their arms “tied behind their back” by such restrictions. He said that the FDA’s rules were vague, and he urged the agency to allow industry to use “postapproval clinical trials … post hoc analyses, subpopulation analysis, observational data, real world evidence, and physician treatment guidelines” to support claims about off-label uses. These presenters were followed by public interest groups and patients who said that they were harmed by off-label uses of drugs and devices promoted by manufacturers…
The FDA requires two well-conducted clinical trials demonstrating statistically significant results in favor of a drug for efficacy approval. While this is a permissive standard, the FDA at least adheres to one important element of analysis not strictly enforced by journal editors or in other venues – they require statistical separation in the declared a priori defined primary outcome variables for approval. On the other hand, this request for the FDA to "allow industry to use ‘postapproval clinical trials … post hoc analyses, subpopulation analysis, observational data, real world evidence, and physician treatment guidelines’ to support claims about off-label uses" is literally a listing of areas where efficacy has regularly been misreported using "outcome switching" among the many other methods of introducing bias. Given industry’s track record over the last several decades, it is the height of hubris to even suggest such changes.
br
s) n.
PhARMA may not be the only corrupting/distorting influence in the “mental health” system, but this is a chilling reminder of PhARMA’s malign influence on the whole system. In the face of profit, truth and patient welfare drop away from PhARMA’s gaze.
Instead of granting PhARMA’s requests, strict criminal, civil and regulatory controls should apply, enforced via individual and corporate liability.
I keep wondering when all individual and institutional players in the “mental health” industry will realize they are in bed with Dracula.
That’s rich… they want to use physician treatment guidelines to support claims about off-label uses. Excuse me! There is a general perception that such treatment guidelines are compromised by conflict of interest and manipulated by Pharma. Hubris indeed.
Some off the best off-label indications are for off-patent drugs. Of course there’s no financial incentive to promote them.
Why the government should make extra allowances for an industry that has had to pay roughly 20 billion dollars in fines to the US Dept of Justice for lying to and bribing doctors, and defrauding Medicaid, is completely beyond me. Shouldn’t they be under very close scrutiny, even some ‘extreme vetting’?
I’d tell them if you like freedom fine, you can promote it whatever way you want but say goodbye to your licensed monopoly, because that cuts into freedom too.
That simple statement would quickly be answered with stunned silence followed by an Emily Latella, “Never mind.”
Speaking of physician treatment guidelines, check this out for a case study in manipulation.