[We are pleased to present this guest article by Dr. McMenamin, who was a practicing emergency physician before turning his sights to the practice of law. He is currently a partner at McGuireWoods LLP specializing in health-related litigation.]
By: Joseph McMenamin, MD, JD
Before a pharmaceutical company may lawfully sell a new drug in the US, the FDA requires a showing of safety and efficacy. Assembling sufficient data is costly in dollars and time. Even then, relatively few humans are actually exposed to new drugs in pre-marketing clinical trials. Typically no more than a few thousand subjects, sometimes fewer are exposed compared to the hundreds of thousands or even millions that are exposed when drugs go on the market.
Hence, rare side effects may go unrecognized pre-launch.
As iMedicalApps readers well know, patients are using social media for a dizzying and ever-expanding array of medically-related reasons: discussing health conditions on PatientsLikeMe, looking up symptoms on Wikipedia, blogging about illnesses, and offering one another moral support. The unanswered question is to what extent, if any, should companies monitor the Internet for chatter about adverse events regarding drugs and medical devices ?
Federal law requires pharmacy companies to report adverse effects arising from post-approval use of their products. This is primarily done using the Adverse Event Reporting System (“AERS”).
The definition of adverse drug experience is quite broad:
Any adverse event associated with the use of a drug in humans, whether or not considered drug related, including the following: An adverse event occurring in the course of the use of a drug product in professional practice…and any failure of expected pharmacological action. [21 CFR 314.80 (a), emphasis added]
The reporting obligation is also broad:
Each applicant…shall promptly review all adverse drug experience information obtained or otherwise received by the applicant from any source, foreign or domestic, including information derived from commercial marketing experience, postmarketing clinical investigations, postmarketing epidemiological/surveillance studies, reports in the scientific literature, and unpublished scientific papers [21 CFR 314.80 (b), emphasis added].
The consequences of non-compliance can be dire. The FDA may withdraw approval of the application and, thus, prohibit continued marketing of the drug product. Once the company reports, it has ongoing responsibilities to investigate. Moreover, once the applicant learns of an adverse drug experience, there is a requirement to maintain records respecting the event for 10 years.
Often, patients make remarks critical of medicines and devices used in their care, or suggest that these products have harmed them. In all probability, many, if not most of these complaints are unfounded. Given the regulations above, however, implausibility of a complaint does not appear to relieve industry of its reporting duties.
Once a company learns of a complaint on, say, Twitter, what is it to do with that information? Critics will damn them for invading privacy; critics will do the same if companies miss real adverse effects that surveillance might have detected. Despite promises it would do so, the FDA still has not answered questions such as these. A couple of years ago, it did furnish some insights in a different context. FDA, “Guidance for Industry: Postmarketing Adverse Event Reporting for Nonprescription Human Drug Products Marketed Without an Approved Application,” (July 2009), indicates that a report is not required unless four criteria are met: there must be an identifiable patient, an identifiable reporter, a suspect drug, and an adverse event.
As the FDA emphasizes, a guidance document represents the agency’s current thinking, but does not create or confer any rights and does not operate to bind the FDA or the public. Absent a more current, social media-specific document, however, this may be the best clue to the FDA’s current thinking on the subject.
The reporting mechanism is designed to advance safety objectives, and some evidence suggests it has succeeded. See, e.g., D.K. Wysowski and L. Swartz, 2005. In other respects, however, regulatory law has not kept up with technology.
The FDA’s reticence notwithstanding, some companies (Astra Zeneca, Roche, e.g.) have addressed these matters with thoughtful, formal writings. The Association of the British Pharmaceutical Industry (ABPI) – a British trade association roughly comparable to the Pharmaceutical Research and Manufacturers of America (PhRMA), has issued a white paper, “Pharmacovigilance and the Internet: A Call for Change” and another document, “Guidance Notes on the Management of Adverse Events and Product Complaints from Pharmaceutical Sponsored Websites”. These provide some assistance, though of course are not law.
In December 2011 the FDA published “Responding to Unsolicited Requests for Off-Label Information about Prescription Drugs and Medical Devices.” As the title suggests, this Guidance focuses on request for off-label information, and so does not fill the prescription. It does acknowledge the rise of social media, which FDA sees as public fora, limiting how a company may reply to inquiries. What is needed, and the sooner the better, is clear Guidance on point.