Sometimes, the drug makers like to skip the research required to get a drug approved for a new indication. An analsyis out of Harvard Med school and the Brigham looked at whistleblower complaints and found that “off-label marketing practices have a broad reach.” And, it’s not a good one.
Similar behaviors and strategies were linked to manufacturers of varying sizes across drugs in virtually all therapeutic classes; they extended to many aspects of the health care system; they affected a multitude of players (prescribers, pharmacies, disease advocacy groups, CME organizations, consumers); and were pursued through virtually every facet of physician-industry relationships (paid consultancies, preceptorships, and collaboration in clinical trials and research publications). The alleged tactics in our analytic sample ranged from subtly encouraging physicians to ask for information about off-label uses to providing strong financial rewards for encouraging off-label uses; they also included targeting multiple links in the prescription production chain, from company scientists and sales representatives to prescribers.
One section details allegations of effort bu some companies to promote the illegal marketing of off label uses.
Thirty-seven of the whistleblower (90%) complaints detailed particular internal manufacturer practices intended to bolster the off-label marketing (two of the four complaints where these were not mentioned were filed solely by whistleblowers positioned outside the companies). All of the practices described were reported to be company-wide, rather than the work of an individual manager or group of managers. In 73% (27/37) of these cases, the off-label marketing strategy was implemented through intramural meetings and seminars in which marketing practices were discussed; in 46% (17/37) of them, it was also implemented through development of brochures and other materials for dissemination; in 51% (19/37), employees other than the sales representatives, such as internal physicians and scientists, were involved.
Many of the complaints describing internal practices (25/37, 68%) pointed to specific efforts by drug manufacturers to conceal off-label marketing activities. Some described warnings from legal teams to avoid off-label marketing (16/25, 64%). These were generally understood by employees as providing “plausible deniability” to the company 33, and were widely undermined through strategies such as verbal orders diverging from what was declared in their company policies 31. For example, one whistleblower reported that his company purposefully designed “do not detail” labels on materials related to off-label uses that could easily be removed by a sales representative 30. A third of complaints included reports of direct orders to conceal, such as “cleaning” internal reports and memoranda of all mentions of off-label marketing (12/25, 48%).
The complaints frequently described use of financial incentives for employees to engage in off-label marketing. Forty-one percent (15/37) of the reports of internal strategies described incentives or other aspects of employees’ compensation plans that were directly tied to effectively implementing an off-label prescription strategy. In one case involving a drug approved by the FDA for a rare indication, a whistleblower reported that the company imposed sales quotas on representatives that could only be met through expanding use beyond the limited approved indication 31. Other examples included an internal sales “contest” for employees who could demonstrate greatest compliance with marketing programs encouraging off-label use 44 and direct payments to employees to encourage them not to report off-label marketing practices 35.
The conclusion
Off-label marketing has been ubiquitous in the health care system and features some behaviors and strategies that may be resistant to external regulatory approaches. Our findings suggest that no regulatory strategy will be complete and effective without physicians themselves serving as a bulwark against off-label promotion. Aside from sales representatives and other company insiders, who play important roles as whistleblowers, physicians are alone in having a full view of many of the most insidious forms of illegal marketing outlined in the complaints we reviewed. As physicians’ understanding of these practices and the consequences of inappropriate off-label promotion for public health evolves, so may their enthusiasm for shutting them down.
Free access to the full study in PLoSMedicine