Science and Law
26th April 2013

Scientific Lessons from the Yaz-Yasmin Gallbladder Legal Settlement

Bayer recently agreed to settle lawsuits alleging that the company’s Yasmin and Yaz oral contraceptive products caused gallbladder injuries. In the settlement, Bayer agreed to pay up to $24 million to settle gallbladder injury claims consolidated in the U.S. District Court for the Southern District of Illinois, as well as in state courts in California, New Jersey and Pennsylvania.

Scientific Lessons from the Yaz-Yasmin Gallbladder Legal Settlement

Bayer recently agreed to settle lawsuits alleging that the company’s Yasmin and Yaz oral contraceptive products caused gallbladder injuries. In the settlement, Bayer agreed to pay up to $24 million to settle gallbladder injury claims consolidated in the U.S. District Court for the Southern District of Illinois, as well as in state courts in California, New Jersey and Pennsylvania.                                  © Deklofenak | Dreamstime Stock Photos

Combined oral contraceptive (COC) agents, first approved in 1960, contain a combination of progesterone and estradiol to inhibit female fertility. Yaz and Yasmin are COC products often referred to as “fourth generation” because they utilize the fourth class of progestin discovered as the drug’s mechanism of action. According to Bayer’s press release, each injured plaintiff would receive $2000 if she presented with injury to the gall bladder (presumably passed gall stones or some other presenting symptom) and $3000 if she required gall bladder removal surgery.

In the corporate scheme of things, the settlement does not represent a lot of money, nor does it come close to the settlement that Bayer agreed to for claims that these agents caused thromboembolic events (one settlement for these allegations has been reported at a billion dollars). However, one would assume, based on the settlement, that there is some form of reliable scientific evidence demonstrating a link between exposure to these COC agents and gallbladder disease. A small amount of scientific research reveals that this is not the case.

We provide below an overview of the science (or lack thereof) linking Yaz or Yasmin to gallbladder disease. This assessment highlights the method of review we have proposed in previous posts (see, for example, here and here) and is a nice case study demonstrating how the evidence should be evaluated and presented.

No Controlled Scientific Studies Supporting Causation

A search of PubMed for all scientific articles ever published with any mention of Yaz, Yasmin, or drosperinone in combination with the term “gallbladder” yields only two scientific articles. The first interesting finding was that there was not even a single, uncontrolled anecdotal case report published in the peer-reviewed scientific literature.

But what did the two controlled studies find?

One article, a retrospective cohort study, reports a small increased relative risk, but clearly dismisses the significance of that association:  “the small effect sizes compounded with the possibility of residual biases in this observational study make it unlikely that these differences are clinically significant.” The other study, a nested case-control analysis of the UK General Practice Research Database, found no evidence of an association.

Thus, based on an evaluation of the available controlled scientific studies of Yaz and Yasmin, there is no reliable evidence supporting an association, let alone a causal link, between these agents and gallbladder disease.

No Spontaneous Reporting Signals

Setting aside the lack of controlled evidence from protocol-driven studies (i.e., the type of studies that have been performed to date and described above), let’s look at data from more anecdotal, spontaneous reporting? We performed an informal evaluation of the FDA’s Adverse Event Reporting System (AERS) in an effort to find  disproportionate reporting of gallbladder events in women prescribed drosperinone-containing COCs compared to other drugs in the system. While this is a broad and nonspecific analysis, one would certainly expect some evidence of disproportionate reporting if a causal link existed. No such disproportions were identified.

The Bottom Line

Thus, no evidence from controlled observational studies or from anecdotal, uncontrolled, spontaneous reporting systems bolsters claims that Yaz or Yasmin cause gallbladder disease. This statement does not represent an opinion or reflect corporate spin. It is based on the available facts. As a scientific matter, it is difficult to imagine how plaintiffs could formulate a persuasive argument that Yaz or Yasmin is capable of causing gallbladder injury in general (general causation) or that Yaz or Yasmin caused gallbladder injury in an individual plaintiff (specific causation).

Bayer’s decision to settle the Yasmin-Yaz cases sets an unfortunate precedent and potentially opens the floodgates for claims with no scientific basis for causation. But scientific methods lead to powerful information that can strengthen a company’s case.

About Innovative Science Solutions

Innovative Science Solutions (ISS) is a leading scientific consulting firm for the worldwide pharmaceutical, biotechnology, and medical device industries. We are an expert team of scientists, regulatory strategists, and consultants providing a wide range of fully-integrated services to industry and counsel including:

Scientific Support to Counsel (Scientific Analysis, Scientific Strategy, Expert ID)

FDA Drug and Medical Device Advisory Committee Review Services

Regulatory Strategy Development

Dietary Supplement Claim Substantiation and Defense Services

Scientific Due Diligence

ISS’ proprietary, cloud-based platform, DataTrove®::Collaboraton Tool, is designed specifically for integrating resources, project management, and team interaction in one secure portal. Fill out the form below to be contacted to schedule your FREE demo!

  • Hidden
  • This field is for validation purposes and should be left unchanged.

From FDA Advisory Committee meetings to complex litigation support, ISS delivers specialized solutions for your business hurdles. With over 13 years of experience, let our proven blend of success and innovation work for you.

Recent Related Articles

Dr. David Schwartz’s IADC Presentation: The Use of Genetic Testing in the Courtroom [Download Slides]
15 July 2020
Dr. David Schwartz’s IADC Presentation: The Use of Genetic Testing in the Courtroom [Download Slides]

On Wednesday July 8, 2020, Dr. David Schwartz of Innovative Science Solutions presented at the IADC 2020 Virtual Annual Meeting on a panel titled The Use of Genetic Testing in the Courtroom. A complimentary copy of the panel presentation is now available for download. Read more

The Use of Genetic Testing in the Courtroom: Dr. David Schwartz will be Presenting at the IADC 2020 Virtual Annual Meeting
02 July 2020
The Use of Genetic Testing in the Courtroom: Dr. David Schwartz will be Presenting at the IADC 2020 Virtual Annual Meeting

Dr. David Schwartz of Innovative Science Solutions will be presenting at the IADC 2020 Virtual Annual Meeting on a panel titled The Use of Genetic Testing in the Courtroom. Read more

WEBINAR ANNOUNCEMENT: What’s in Those Genes?
12 June 2020
WEBINAR ANNOUNCEMENT: What’s in Those Genes?

Genetic Evidence Concerning Causation for Mesothelioma 16 June 2020 at 2pm Eastern Daylight Time. Read more

Talc and Asbestos Defendants Should Monitor and Utilize Published Studies Linking Mesothelioma to Genomic Causes
28 April 2020
Talc and Asbestos Defendants Should Monitor and Utilize Published Studies Linking Mesothelioma to Genomic Causes

Plaintiff experts having been asserting for decades that all mesotheliomas must be linked to some asbestos exposure. Indeed, this has led to the erroneous (but widespread) view that mesothelioma is a signature disease, only caused by asbestos exposure. Read more

Let’s work together

The journey to scientific and commercial success is often complex and always critical, if you are looking for an expert partner to help steer you to confident solutions, contact us today

Contact us