For those litigating drug cases, the NEJM just published an open access article with a broad set of data on medical marketing. It’s online here at NEJM.  The abstract is pasted below.


“Key Points

Question  How has the marketing of prescription drugs, disease awareness, health services, and laboratory tests in the United States changed from 1997 through 2016?

Findings  From 1997 through 2016, medical marketing expanded substantially, and spending increased from $17.7 to $29.9 billion, with direct-to-consumer advertising for prescription drugs and health services accounting for the most rapid growth, and pharmaceutical marketing to health professionals accounting for most promotional spending.

Meaning  There has been marked growth in expenditures on and extent of medical marketing in the United States from 1997 through 2016.


Importance  Manufacturers, companies, and health care professionals and organizations use an array of promotional activities to sell and increase market share of their products and services. These activities seek to shape public and clinician beliefs about laboratory testing, the benefits and harms of prescription drugs, and some disease definitions.

Objective  To review the marketing of prescription drugs, disease awareness campaigns, health services, and laboratory tests and the related consequences and regulation in the United States over a 20-year period (1997-2016).

Evidence  Analysis (1997-2016) of consumer advertising (Kantar Media data for spending and number of ads); professional marketing (IQVIA Institute for Human Data Science, Open Payments Data [Centers for Medicare & Medicaid Services]); regulations and legal actions of the US Food and Drug Administration (FDA), Federal Trade Commission (FTC), state attorneys general, and US Department of Justice; and searches (1975-2018) of peer-reviewed medical literature (PubMed), business journals (Business Source Ultimate), and news media (Lexis Nexis) for articles about expenditures, content, and consequences and regulation of consumer and professional medical marketing. Spending is reported in 2016 dollars.

Findings  From 1997 through 2016, spending on medical marketing of drugs, disease awareness campaigns, health services, and laboratory testing increased from $17.7 to $29.9 billion. The most rapid increase was in direct-to-consumer (DTC) advertising, which increased from $2.1 billion (11.9%) of total spending in 1997 to $9.6 billion (32.0%) of total spending in 2016. DTC prescription drug advertising increased from $1.3 billion (79 000 ads) to $6 billion (4.6 million ads [including 663 000 TV commercials]), with a shift toward advertising high-cost biologics and cancer immunotherapies. Pharmaceutical companies increased DTC marketing about diseases treated by their drugs with increases in disease awareness campaigns from 44 to 401 and in spending from $177 million to $430 million. DTC advertising for health services increased from $542 million to $2.9 billion, with the largest spending increases by hospitals, dental centers, cancer centers, mental health and addiction clinics, and medical services (eg, home health). DTC spending on advertising for laboratory tests (such as genetic testing) increased from $75.4 million to $82.6 million, although the number of ads increased more substantially (from 14 100 to 255 300), reflecting an increase in less expensive electronic media advertising. Marketing to health care professionals by pharmaceutical companies accounted for most promotional spending and increased from $15.6 billion to $20.3 billion, including $5.6 billion for prescriber detailing, $13.5 billion for free samples, $979 million for direct physician payments (eg, speaking fees, meals) related to specific drugs, and $59 million for disease education. Manufacturers of FDA-approved laboratory tests paid $12.9 million to professionals in 2016. From 1997 through 2016, the number of consumer and professional drug promotional materials that companies submitted for FDA review increased from 34 182 to 97 252, while FDA violation letters for misleading drug marketing decreased from 156 to 11. Since 1997, 103 financial settlements between drug companies and federal and state governments resulted in more than $11 billion in fines for off-label or deceptive marketing practices. The FTC has acted against misleading marketing by a single for-profit cancer center.

Conclusions and Relevance  Medical marketing increased substantially from 1997 through 2016, especially DTC advertising for prescription drugs and health services. Pharmaceutical marketing to health professionals accounted for most spending and remains high even with new policies to limit industry influence. Despite the increase in marketing over 20 years, regulatory oversight remains limited.”

The scale of mass tort litigation is sometimes missed. The scale of “mesh MDL litigation” is nicely captured in a February 5, 2018 post by Jim Beck at the Drug & Device blog, aptly titled “The Lawyer Full Employment Action of 2018.”

The post provides a good overview of the timeline for the MDL case, and some calculations on depositions. For example, under one set of assumptions outline by Jim, there could be over 92,000 depositions. That will never happen, but the calculations and implications deserve consideration when seeking to understand the economics and demands of the litigation industry.

Pasted below is a fascinating press release from a proteomics company known as SomaLogic. The gist is the scientists were able to predict adverse effect problems with an experimental drug using SomaLogic’s molecular tools for measuring the amounts of proteins circulating in persons who were part of a clinical trial of the drug. The entire area of proteomics is fascinating and offers great potential for, among other things, better understanding of diseases and risks. This work by SomaLogic provides an exciting example of how new “omic” knowledge will create incredible changes in civil litigation issues. The full press release is pasted below and is well worth reading.


“Protein changes in blood can provide early warning of potential harmful side effects from experimental drug candidates

In an article published “early online”in the American Heart Association journal Circulation, researchers at Pfizer, the Karolinska Institute, the University of California, San Francisco and SomaLogic describe how the measurement of blood-based protein changes in response to treatment with an experimental drug candidate may improve the efficiency and safety of clinical drug development. The published study used a nine-protein-based risk score to detect potential cardiovascular problems with a drug candidate (torcetrapib) well before significant adverse symptoms manifested themselves in patients in the drug’s clinical trial. Their analysis also identified changes in approximately 200 additional proteins that help describe the biology behind those adverse symptoms, which is applicable more broadly in cardiovascular disease management.

Pfizer’s phase three clinical trial (named “ILLUMINATE”) of torcetrapib, a drug candidate that had been shown to raise levels of “good”cholesterol and lower levels of “bad”cholesterol, was expected to confirm its blockbuster potential in reducing the risk of serious cardiovascular events such as heart failure and stroke. Instead, ILLUMINATE was halted abruptly in 2006 due to an unexpected increase in deaths and cardiovascular problems in trial subjects receiving the new drug candidate. At the time the trial was halted, Pfizer had invested 15 years and nearly a billion dollars in developing torcetrapib.
The Circulation study describes an attempt to determine if the problems from torcetrapib treatment could have been detected earlier, and thus at a lower cost. In this study, the researchers used the SOMAscan®assay to measure changes in the levels of over 1,000 proteins in blood samples from ILLUMINATE trial participants. Using a previously validated, nine-protein cardiovascular risk score, they found that they could successfully predict the harmful effects of torcetrapib in specific patients after only three months of treatment—much earlier than the point at which the ILLUMINATE trial was terminated (18 months).
In addition, a wider analysis of approximately 200 blood proteins that significantly changed in torcetrapib-treated patients revealed that the drug candidate had widespread, unexpected effects on normal immune and inflammatory processes. In addition, changes in only eight of the proteins measured were sufficient to explain the biology underlying the hypertension side effect seen in clinical trials. Beyond torcetrapib, these insights can also provide additional guidance for more personalized and targeted prescribing of currently marketed cardiovascular drugs, such as statins and ACE inhibitors.
Torcetrapib is just one member of a promising class of cardiovascular disease-prevention drugs, cholesteryl ester transferase (CETP) inhibitors, that have garnered considerable interest from the pharmaceutical industry. In addition to Pfizer, both Eli Lilly and Roche had candidate CETP inhibitors that were dropped late in development due to lack of efficacy. However, Merck recently announced that their drug candidate anacetrapib successfully completed the longest CETP clinical trial to date.

Expanding the work described in the Circulation paper to include comparative analyses from all of these drug candidate trials from different companies could provide, not only enhanced understanding of critical protein changes related to side effects, but could also reveal early signs of “positive”protein changes that would help accelerate the successful development of more promising candidates from not only this drug, but across many different classes and even disease types.

Reference: Williams, SA et al. (2017) “Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib” Circulation (published early online October 3, 2017).
Fintan R. Steele, Ph.D.
Chief Communications Officer
T: 720-214-3080
C: 617-816-9834

About SomaLogic

SomaLogic is committed to helping people worldwide receive timely, accurate, trustworthy and actionable information that helps them manage their personal health and wellness. To realize this vision, we are creating and delivering the ”SOMAscan Platform,”a clinically useful and affordable health information system based on comprehensive and personalized protein measurement, delivered broadly through a global ecosystem of partners and users.

The good news for drug companies is that a federal judge in New York agrees there is a 1st Amendment right to provide information to consumers about off label uses of FDA approved drugs. The not so good news is that various defense oriented lawyers think those actions will take away FDA preemption arguments that drug companies depend on in many cases. For example, consider this quote from an August 10, 2015 article at LAW360:

In theory, this ruling frees companies to promote their drugs more broadly for uses not approved by the FDA, so long as what they say is truthful and not misleading,” Jennifer Bragg of Skadden Arps Slate Meagher & Flom LLP said.

“But any arguments that companies might have previously had that their statements were consistent with FDA’s approval will not be available, to the extent that cases pertain to alleged injuries from off-label uses of their products,” she said.

Be careful what you wish for ….

Manufacturers increasingly need to think about "cradle to grave" expenses for products. A new example arises from drugs. Some people link drugs in water to various diseases. Therefore, some want better disposal of unused drugs – some of the facts are outlined in a brief article from Harvard online.

Now, in a next step, a federal judge this week upheld a statute requiring drug manufacturers to bear the expense of "take back" programs intended to replace sloppy disposal. The opinion is online, courtesy of AmLaw. An article from the Recorder explains: 

"SAN FRANCISCO — Ruling over industry objections, U.S. District Judge Richard Seeborg is allowing Alameda County to move forward with a program that compels pharmaceutical companies to pay for the safe disposal of unused prescription drugs.

Last summer, the Alameda Board of Supervisors passed an ordinance — believed to be the first of its kind in the country — that requires companies that manufacture prescription drugs sold or distributed in the region to fund "take-back programs," sparing the county the expense.

A coalition of industry associations filed suit in U.S. District Court for the Northern District of California in December, arguing that the law burdened interstate commerce.

Drug companies would likely raise prices to fund the county initiative, forcing consumers nationwide to bankroll a program that only benefits Alameda County residents, lawyers at Jones Day had argued in a motion for summary judgment on behalf of the trade groups in Pharmaceutical Research and Manufacturers of America v. County of Alameda, 12-6203."


Read more:

Thalidomide claims are back in the popular press after a newly announced settlement  in a class action case pending in Australia; the case was filed by Australia’s Peter Gordon. The claims are significant for several reasons, including the fact that they involve new claims involving old drugs, and modern science can now further explain such injuries.  The case apparently involves a new settlement for several million dollars, as described in an article from the Washington Post.

Over 50 years ago, thalidomide was marketed for pregnant women as a drug said to reduce morning sickness.  As it turned out, the drugs consumed by the mothers resulted in extensive birth defects in over 10,000 children in many countries. Accordingly, a relatively small amount of litigation went mainly through the UK after the world learned that pregnant mothers who took thalidomide sometimes gave birth to children without arms or legs on either side of their bodies, a condition known as phocomelia.  Later, a modest compensation UK fund was established, and then occasionally “topped up.”

Today, new thalidomide claims are being brought in courts around the world as plaintiffs seek compensation for injuries now better understood due to new work in molecular biology.  For example, plaintiff’s lawyers now can and do point for support to a 2009 study published in the Proceedings of the National Academy of Sciences. The study provided insights into the molecular biology of how, why and when thalidomide blocks blood vessel formation. More recently, Japanese scientists used zebrafish and chicks to find further specifics about the workings of thalidomide. They then published a 2010 paper which identifies the protein to which thalidomide binds, thereby disrupting normal bodily processes. Thus, today, scientists appear to have found and provided a pretty thorough explanation of a bodily harm process that was a mystery fifty years ago.