The lawsuit industry spends many millions of dollars each year to persuade people that they are ill from the medications they use, and that lawsuit industry lawyers will enrich them for their woes. But does the lawyer advertising stimulate the reporting of adverse events by consumers’ filing of MedWatch reports in the Federal Adverse Event Reporting System (FAERS)?
The question is of some significance. Adverse event reporting is a recognized, important component of pharmacovigilence. Regulatory agencies around the world look to an increased rate of reporting of a specific adverse event as a potential signal that there may be an underlying association between medication use and the reported harm. In the last two decades, pharmacoepidemiologists have developed techniques for mining databases of adverse event reports for evidence of a disproportionate level of reporting for a particular medication – adverse event pair. Such studies can help identify “signals” of potential issues for further study with properly controlled epidemiologic studies.[1]
One of the vexing misuses of pharmacovigilance techniques in the pharmaceutical products litigation is the use of adverse events reporting, either as case reports or in the form of disproportionality analyses to claim causal inference. In some litigations, lawsuit industry lawyers have argued that case reports, in the FAERS, standing alone support their claims of causation.[2] Desperate to make their case through anecdotes, plaintiffs’ counsel will sometimes retreat to the claim that they want to introduce the MedWatch reports in support of a lesser claim that the reports put the defendant on “notice.” Typically, the notice argument leaves open exactly what the content of the notice is, but the clear intent is to argue notice that (1) there is an increased risk, and (2) the defendant was aware of the increased risk.[3]
Standard textbooks on pharmacovigilance and pharmacoepidemiology, as well as regulatory agency guidance, emphatically reject the use of FAERS anecdotes or their transmogrification into disportionality analyses (DPAs) to support causal claims. The U.S. FDA’s official guidance on good pharmacovigilance practices, for example, elaborates on DPAs as an example of data mining, and instructs us that:
“[d]ata mining is not a tool for establishing causal attributions between products and adverse events.”[4]
The FDA specifically cautions that the signals detected by data mining techniques should be acknowledged to be “inherently exploratory or hypothesis generating.”[5] The agency exercises caution when making its own comparisons of adverse events between products in the same class because of the low quality of the data themselves, and uncontrollable and unpredictable biases in how the data are collected.[6] Because of the uncertainties in DPAs, the FDA urges “extreme causation” in comparing reporting rates, and generally considers DPA and similar analyses as “exploratory or hypothesis-generating.”[7]
The European Medicines Agency offers similar advice and caution:
“Therefore, the concept of SDR [Signal of Disproportionate Reporting] is applied in this guideline to describe a ‘statistical signal’ that has originated from a statistical method. The underlying principle of this method is that a drug–event pair is reported more often than expected relative to an independence model, based on the frequency of ICSRs on the reported drug and the frequency of ICSRs of a specific adverse event. This statistical association does not imply any kind of causal relationship between the administration of the drug and the occurrence of the adverse event.”[8]
Because the lawsuit industry frequently relies upon and over-endorses DPAs in its pharmaceutical litigations, inquiring minds may want to know whether the industry itself is stimulating reporting of adverse events through its media advertising.
Recently, two investigators published a study that attempted to look at whether lawsuit industry advertising was associated with stimulation of adverse event reporting in the FAERS.[9] Tippett and Chen conducted a multivariate regression analysis of FAERS reporting with independent variables of Google searches, attorney advertising, and FDA actions that would affect reporting over the course of a single calendar year (mid-2015 to mid-2016). The authors analyzed 412,901 adverse event reports to FAERS, involving 28 groups of drugs that were the subject of solicitous advertising.
The authors reported that they found associations (statistically significant, p < 0.05) for regression coefficients for FDA safety actions and Google searches, but not for attorney advertising. Using lag periods of one, two, three, and four weeks, or one or two months, between FAERS reporting and the variables did not result in statistically significant coefficients for lawyer advertising.
The authors variably described their finding as “preliminarily” supporting a claim that FAERS reporting is not stimulated by “direct attorney submission or drug injury advertising,” or as failing to find “a statistically significant relationship between drug injury advertising and adverse event reports.”[10] The authors claim that their analyses show that litigation advertisements “do not appear to have spurred patients, providers, attorneys, or other individuals to file a FAERS report, as shown in our regression and graphical results.”[11]
There are substantial problems with this study. For most of the 28 drugs and drug groups studied, attorneys made up a very small proportion of all submitters of adverse event reports. The authors present no pre-study power analysis for this aspect of their study. The authors do not tell us how many analyses they have done before the one presented in this journal article, but they do acknowledge having done “exploratory analyses.” Contrary to the 2016 guidance of the American Statistical Association,[12] they present no actual p-values, and they provide no confidence or prediction intervals for their coefficients. The study did not include local television advertising, and so the reported statistical non-significance of attorney advertising must be qualified to show the limitations of the authors’ data.
Perhaps the most serious problem with this observational study of attorney advertising and stimulated reporting is the way in which the authors framed their hypothesis. Advertising stimulates people to call the toll-free number to learn more how they too may hit the litigation jackpot. The point of attorney advertising is designed to persuade people to become legal clients, not to file MedWatch forms. In the following weeks and months that follow, paralegals interview the callers, collect information, and only then FAERs happen. Lag times of one to four weeks are generally irrelevant, as is the hypothesis studied and reported upon in this article.
After decades of working in this area, I have never seen an advertisement that encourages filing a MedWatch report, and the authors do not suggest otherwise. Advertising is only the initial part of a client intake mechanism that would result in the viewers’ making a telephone call, with a subsequent interview by lawfirm personnel, a review of the putative claim, and the viewers’ obtaining and signing retainer agreements and authorizations to obtain medical records. The scope of the study, which looked at FAERS filings and attorney advertisements after short lag periods could not detect an association given how long the recruitment takes.
The authors speculate, without evidence, that the lawsuit industry may discourage their clients from filing MedWatch reports and that the industry lawyers may hesitate to file the reports to avoid serving as a fact witness in their client’s case.[13] Indeed, the authors themselves adduce compelling evidence to the contrary, in the context of the multidistrict litigation over claimed harms from the use of testosterone therapies.
In their aggregate analysis of the 28 drugs and drug groups, the authors found that the lawsuit industry submitted only six percent of MedWatch reports. This low percentage would have been much lower yet but for the very high proportion (68%) of lawyer-submitted reports concerning the use of testosterone. The litigation-driven filings lagged the relevant attorney advertising by about six months, which should have caused the authors to re-evaluate their conclusions and their observational design that looked for correlations within one or two months. The testosterone data shows rather clearly that attorney advertising leads to recruitment of clients, which in turn leads to the filing of litigation-driven adverse event reports.
As the authors explain, attorney advertising and trolling for clients occurred in the summer of 2015, but FAERS reporting did not increase until an extreme burst of filings took place several months later. The authors’ graph tells the story even better:
So the correct conclusion is that attorney advertising stimulates client recruitment, which results in mass filings of MedWatch reports.
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[1] Sean Hennessy, “Disproportionality analyses of spontaneous reports,” 13 Pharmacoepidemiology & Drug Safety 503, 503 (2004). See also “Disproportionality Analyses Misused by Lawsuit Industry” (Apr. 20, 2020).
[2] See, e.g., Fred S. Longer, “The Federal Judiciary’s Super Magnet,” 45 Trial 18, 18 (July 2009) (arguing that “adverse events . . . established a causal association between Piccolomal and liver disease at statistically significant levels”).
[3] See, e.g., Paul D. Rheingold, “Drug Products Liability and Malpractice Cases,” 17 Am. Jur. 1, Trials, Cumulative Supplement (1970 & Supp. 2019) (“Adverse event reports (AERs) created by manufacturers when users of their over-the-counter pain reliever experienced adverse events or problems, were admissible to show notice” of the elevated risk.).
[4] FDA, “Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment Guidance for Industry” at 8 (2005) (emphasis added).
[5] Id. at 9.
[6] Id.
[7] Id. at 11.
[8] EUDRAVigilance Expert Working Group, European Medicines Agency, “Guideline on the Use of Statistical Signal Detection Methods in the EUDRAVigilance Data Analysis System,” at 3 (2006) (emphasis added). See also Gerald J. Dal Pan, Marie Lindquist & Kate Gelperin, “Postmarketing Spontaneous Pharmacovigilance Reporting Systems,” in Brian L. Strom & Stephen E. Kimmel and Sean Hennessy, Pharmacoepidemiology at 185 (6th ed. 2020).
[9] Elizabeth C. Tippett & Brian K. Chen, “Does Attorney Advertising Stimulate Adverse Event Reporting?” 74 Food & Drug Law J. 501 (2020) [Tippett].
[10] Id. at 502.
[11] Id.
[12] Ronald L. Wasserstein & Nicole A. Lazar, “The ASA’s Statement on p-Values: Context, Process, and Purpose,” 70 The Am. Statistician 129 (2016).
[13] Tippett at 591.
