The learned intermediary doctrine after FDA's drug watch and PhRMA's clinical study results database: shifting the focus of failure-to-warn claims.

• Author: Scheve, Stephen E.
• Position: Pharmaceutical Researchers and Manufacturers Association

THE learned intermediary doctrine is the cornerstone of almost every pharmaceutical and medical device products liability claim. Recognizing that information about a drug's risks can be conveyed outside a package insert provides fertile ground for debate over the implications of the Drug Watch Web site and Clinical Study Results Database in the context of failure-to-warn claims.

In an attempt "to develop and disseminate important emerging drug safety information concerning marketed drug products to healthcare professionals and patients,"(1) FDA published a draft document on May 4, 2005, entitled "FDA's 'Drug Watch' for Emerging Drug Safety Information," which included plans to create a Web page that would communicate this drug safety information. Seven months prior, the Pharmaceutical Researchers and Manufacturers Association ("PhRMA") launched a database with similar goals. PhRMA's plan, "Clinical Study Results Database," had the twin goals of providing a central, easily accessible database and "making clinical study results for U.S.-marketed pharmaceuticals more transparent." (2) These two sites are not the only sources of such information available on the Web. Both GlaxoSmithKline and Forrest Laboratories have posted clinical trial results on Web sites as a result of agreements with the Attorney General of the State of New York. (3) Other companies have made information available on their own Web sites, as well; (4) however, due to competitive concerns, some companies have been reluctant to post this information. Some companies have been particularly leery of publishing information related to Phase I and Phase II studies of clinical trials. (5) Despite the number of individual sites, FDA's Drug Watch and PhRMA's Clinical Study Results Database sites present two bases for comparison and inquiry with respect to how this medium will impact pharmaceutical products liability litigation. Although dissimilar in many significant respects, the proposed Drug Watch Web site and Clinical Study Results Database sites present a host of similar challenges, pitfalls, and opportunities in pharmaceutical products liability litigation for claimants, defendants (including manufacturers and prescribing physicians), and courts.

The Drug Watch Web site and Clinical Study Results Database are almost certain to impact pharmaceutical products liability litigation by impacting the learned intermediary doctrine. Despite PhRMA's stated intent not to impact prescribing decisions, the information provided on the Drug Watch Web site and Clinical Study Results Database can conceivably either supplement or undermine the warnings provided in the package insert and even create a viable common knowledge defense. In this regard, the Drug Watch program and Clinical Study Results Database present a challenge to traditional reliance on the package insert as the source of warnings in a way not contemplated by the American Law Institute ("ALI") in either the Restatement (Second) or Restatement (Third). Although both FDA and PhRMA caution against excessive reliance on their sites (albeit for different reasons), manufacturers may be able to find safe harbor in these media with respect to products liability suits because they provide warnings to prescribing physicians and patients in a manner that has greater flexibility, increased timeliness, and wider availability than the physician package insert. Claimants will no doubt point to the information on these sites not only to juxtapose it with perceived omissions in the package insert, Physician's Desk Reference, and marketing materials, but also to establish actual or constructive knowledge of certain risks and general causation. These sources pose important questions with respect to a prescribing physician's duty to consult them. In short, the proposed Drug Watch Web site and Clinical Study Results Database present a strong possibility of shifting the focus of failure-to-warn claims away from the physician package insert.

1. Background: Involuntary & Voluntary Reporting

   1. FDA's Drug Watch

      As currently proposed, the purpose of FDA's Drug Watch Web site is to provide information regarding early signals of drug risk while FDA assesses how to react to this information. (6) The Web site is intended to provide information during the "period of uncertainty" before FDA and a drug's sponsor evaluate the emerging risk information. In this respect, Drug Watch differs from the Clinical Study Results Database as the former's content is driven entirely by FDA and is based on adverse experience reports. As FDA has noted, however, manufacturers are the ultimate sources of the information for Drug Watch. The aggregation and communication of this information as an emerging risk, however, are decisions made by FDA.

      FDA considers Drug Watch as a source of information for healthcare professionals. Importantly, with respect to the "unlearned," Drug Watch recognizes and is meant to serve the increasingly active role that consumers are taking in their healthcare. The information that will be posted generally revolves around three nonexclusive categories: (1) serious adverse events associated with the use of a drug that have been reported to FDA; (2) emerging risks associated with a drug "that might be avoided by appropriate patient selection, monitoring, or use of concomitant therapy"; and (3) new information regarding prescribing, dispensing, and use recommendations. (8) Manufacturers' adverse experience reports will be the source of this information which, although previously available through FOIA requests, will be in a readily-accessible medium through the Drug Watch Web site. The quantum of data required for a drug to be posted on Drug Watch is currently unknown, but FDA has indicated that listing drugs on the Drug Watch Web site will take place "only when we believe that the data are significant enough to warrant further consideration to determine whether an actual safety problem exists." (9) The uncertainty of this standard is likely to be a source of contention with respect to how Drug Watch will impact products liability issues.

      The information upon which this decision is based will fall short of FDA's standard of "adequate and well controlled studies" required, for example, with respect to claims of effectiveness. (10) The standard for adequate and well-controlled studies requires, inter alia, that the studies be randomized and double blind. Even when adverse drug experience reports (11) are taken in the aggregate, they represent little more than random case reports which lack details and procedures necessary to permit scientific evaluation. (12) Similar issues are present with respect to GlaxoSmithKline's and Forest Labs' Web sites, which these companies were required to create and maintain under their respective settlement agreements with the New York Attorney General. Under the settlements, these companies are required to post information regarding clinical studies which were "not limited to a research study that is randomized, controlled, or blinded." (13)

      Similar questions are present with respect to removal from the Drug Watch Web site. There is a threshold question with respect to the appropriate standards that must be met to support removal of a drug from Drug Watch. These standards will likely impact how a drug's removal from Drug Watch is treated in litigation. The basis for removal is also important: Does removal from the site mean that the once-supposed risk no longer exists or that the risk is no longer "emerging" and the manufacturer has provided a warning of the risk? If the former, what is the effect of this finding and what weight should it bear? If the latter, there is a legitimate question as to whether the warning provided is entitled to any additional consideration beyond the minimal deference normally afforded to FDA-approved warnings. (14)

      Perhaps because of these concerns, FDA has emphasized that "the information posted on the Drug Watch is information about which FDA has made no regulatory judgment" and "does not mean that FDA has concluded there is a causal relationship between the drug product and the risks or adverse events described." (15) In connection with this position, competing manufacturers are put on notice that promotional comparisons risk violation of the prohibition on false and misleading promotional claims. None of these admonitions or qualifications, however, will insure that this information stays outside the courtroom.

   2. PhRMA's Clinical Study Results Database

      The express goal of the Clinical Study (16) Results Database...