Our readership is tuned into current events and stays up to date on significant drug and device litigation. We bet no one missed that Taylor and Travis are getting married, or that a college football game being hyped as the biggest regular season game in at least a decade (Texas v. Ohio St.) happens tomorrow. We also bet that the blog’s readers know what GLP-1 inhibitors are—medications developed for diabetes and now widely prescribed for weight loss. At least one poll estimated that 12% of the U.S. population has taken a GLP-1 medication.
About a year ago, we posted about the successful efforts of the defendants in the GLP-1 MDL to have the court, rather than permitting unfettered discovery at the outset, instead tee-up certain “cross-cutting” issues that would impact the scope of the MDL. Yesterday we posted about the MDL court’s ruling on preemption of the plaintiffs’ design defect claims. Today we address a separate decision addressing the admissibility of expert testimony on a cross-cutting issue. In re Glucagon-Like Peptide-1 Receptor Agonists Prods. Liab. Litig., MDL No. 3094, 2025 WL 2396801 (E.D. Pa. Aug. 15, 2025).
The cross-cutting issue is whether a physician can reliably diagnose a patient with gastroparesis without performing a gastric emptying study. That’s an important issue in the MDL, as approximately 95% of the claims in the MDL allege gastroparesis (“paralysis of the stomach, [which] occurs when a patient’s stomach, regardless of the underlying cause, fails to move solid foods through the digestive track.”). Id. at *2. The parties and their experts agreed that a diagnosis of all types of gastroparesis—except drug-induced gastroparesis—requires (1) the patient to exhibit upper GI symptoms, (2) confirmation that the symptoms are not caused by an obstruction or other mechanical factor, and (3) delayed gastric emptying confirmed with an objective, gastric emptying study. Id. at *3.
For drug-induced gastroparesis, plaintiffs’ experts claimed that a reliable diagnosis could be made with a differential diagnosis instead of a gastric emptying study (we’ve blogged about differential diagnoses that didn’t satisfy Rule 702, including here, here and here). Although recognized in the Third Circuit, “the mere statement by an expert that he or she applied a differential diagnosis in determining causation does not ipso facto make that application scientifically reliable or admissible.” Id. at *10 (quoting Soldo v. Sandoz Pharms. Corp., 244 F. Supp. 2d 434, 551 (W.D. Pa. 2003)). Rather, the methodology for a differential diagnosis must be properly supported in order to be reliable and admissible.
The court considered a comprehensive medical review provided by the defendants as to the established medical consensus for the diagnosis of all types of gastroparesis. Based on that review, it was clear that using a differential diagnosis instead of accepted, objective testing was “at odds with the medical consensus on what inputs are required to reliably diagnose a patient with gastroparesis, including the drug-induced gastroparesis subset.” Id. at *14. So far so good, right? Yes and no.
The court did not mention the recent amendments to Rule 702 and instead cited a number of pre-amendment cases for the proposition that Rule 702 has a “liberal standard for admissibility.” Id. at *9 (we’ve said it before and we’ll say it again: in a post-amendment Rule 702 world, “Don’t Say Daubert”). Viewing the 702 analysis with a “liberal standard for admissibility,” the court looked to whether the plaintiffs’ expert offered a “good explanation” as to why the methodology of using a differential diagnosis instead of the objective testing accepted within the medical community would be reliable. Id. at *15.
Plaintiffs’ gastroenterologist opined that, if a patient vomited undigested food hours after finishing a meal, then that was sufficient evidence of delayed gastric emptying. He identified two retrospective studies which he claimed supported his opinions. But the court’s review of those studies showed that the expert was taking the studies’ conclusions “further than the authors themselves were willing to go.” Id. at *16. At most, one of the studies indicated that the question warranted further consideration by a panel of experts in future consensus documents. The court held there was “simply too great an analytical gap between the research cited and the opinion proffered.” Id. at *17. The court similarly rejected the expert’s attempt to rely on case reports, as those were “not research studies or broadly accepted guidance documents outlining an accepted method of diagnosis.” Id. at *18.
The gastroenterologist also asserted that a differential diagnosis is appropriate to replace objective testing if a patient develops GI symptoms within three months of starting a GLP-1 medication. But the court found two problems with that opinion. One, the doctor had not conducted any testing to determine whether his assumption was correct, and he could not state the known or potential error rate of his assumption. Two, in concluding that delayed gastric emptying is the most likely cause of symptoms within three months of starting the medication, the doctor failed to rule out other potential mechanisms of action where the GLP-1 medications can cause upper GI symptoms. At best, the gastroenterologist’s theory was a “hypothesis which has not yet been subjected to the rigors of science” and was properly excluded. Id. at *23.
The defendants additionally argued that the gastroenterologist’s differential diagnosis methodology was unreliable because it didn’t exclude an alternative diagnosis of functional dyspepsia. Gastroparesis and functional dyspepsia are the two “most common sensorimotor disorders of the stomach,” and they are “usually confused” such that numerous patients are misdiagnosed with gastroparesis when the accurate diagnosis is functional dyspepsia. Id. at *23. Plaintiffs’ expert could not offer a good explanation as to how his differential diagnosis accounted for this, lending further support to the court’s holding that his differential diagnosis approach was not reliable.
Plaintiffs’ proposed radiology expert fared no better. The radiologist opined that, instead of an objective study to evaluate gastric emptying, x-rays, CT scans, MRIs, ultrasounds and barium swallows could be used. The expert could not identify any literature to support his use of these approaches, he had not tested the reliability of his methodology, he had not identified the potential error rate, he had not published his proposed methodology or sought peer review of it, and he had never diagnosed a patient with gastroparesis based on his proposed methodology. Id. at *28-29. As if that wasn’t enough, the expert’s opinions also “frequently changed between his report, his deposition testimony, and his testimony during [an] evidentiary hearing.” Id. at *30. The expert originally identified his proposed techniques as “subjective” during his deposition, but at an evidentiary hearing he changed that to “objective.” That went to the heart of the issue—as the accepted medical guidelines require objective testing. The court held that the radiologist’s opinions were unreliable and properly excluded.
The decision also addressed plaintiffs’ efforts to rely on one of the defendant’s FDA submissions for “regulatory estoppel.” Id. at *33. Plaintiffs claimed that the defendant’s FDA submission included statements that agreed with the approaches espoused by their experts (i.e., suggesting that an objective test was not required and that a differential diagnosis would be acceptable), and that the defendant should be estopped from taking a contrary position in the MDL.
The court first questioned whether “regulatory estoppel” was even a recognized doctrine, and suggested it was not. Nonetheless, it addressed plaintiffs’ arguments and held that, even if the court recognized regulatory estoppel, it would not apply. First, plaintiffs were taking statements in the FDA report out of context, as the report and accompanying literature review did not focus on the diagnosis of gastroparesis. Second, a “holistic” review of the submission showed that it was consistent with the defendants’ position that an appropriate diagnosis of gastroparesis required objective testing. Id. at *34.
This is an in-depth decision that focuses heavily on an extensive set of medical literature and testimony by the experts. Kudos to the defense team for distilling this information into clear, successful arguments. The result is that any plaintiff in the MDL claiming to have drug-induced gastroparesis must have had a gastric emptying study at the time of diagnosis. Absent that, their claims won’t survive. Although the court indicated the ruling would not have a significant impact on the overall size of the MDL since most plaintiffs were claiming permanent gastroparesis (rather than drug-induced), is is certainly a good step in trimming down the MDL.