W-23: Representation of Adult Obese Subjects in Pivotal Clinical Trials for Products approved by FDA in 2015
Rutgers, The State University of New Jersey United States
To determine if obese (body mass index [BMI] = 30.0 kg/m2) adult patients are adequately being represented and considered in clinical trials for recently FDA approved pharmaceutical products.
For the drugs approved by the FDA from January 1 - December 31, 2015, review and analyze the drugs' USPIs, published literature on the pivotal clinical trials, and information collected from the pharmaceutical companies’ medical information departments via medical queries.
45 drugs were approved by the FDA in 2015. Analysis was conducted for 42/45 drugs (Genvoya®, Orkambi®, and Strensiq® were excluded as they have a pediatric indication, which is out of scope for this study).
50% (21) of the drugs have USPIs that contain dosing or clinical information regarding the weight of a patient and its effect on therapy.
• Of the 21 drugs, 12 have weight-based dosing (half of these drugs had oncology indications). The other 9 drugs’ USPIs noted findings from population PK analyses that showed no clinically meaningful effects on drugs’ PK based on weight/BMI. Hence, no dose adjustments were recommended in these USPIs.
Among the other 21 drugs that didn’t contain any information related to weight in the USPIs, 8 had published literature available with information regarding the characteristics of the patient population that was studied.
• Subgroup analyses by weight or BMI were performed within the studies for 5/8 drugs along with PK analyses, which showed no notable effects of weight on the drugs’ PK. Literature for the remaining 3 drugs contained information on the patients’ median BMI in the baseline metabolic characteristics, however no information could be found on how many obese patients were enrolled in the studies or if any analyses were conducted based on BMI/weight.
• The other 13 drugs didn’t have any publicly available information on how many obese patients were enrolled in the studies or if any analyses were conducted based on BMI/weight. However, upon querying the medical information departments of their respective pharmaceutical companies, 4 drugs had information regarding the PK analyses conducted based on BMI/weight (showing no clinical significance of weight on the therapy), 4 drugs only had information regarding the enrolled patients’ median weight and/or BMI (no information on any subgroup analyses conducted based on BMI/weight or how many obese patients were enrolled), and 5 drugs had no available pertinent information.
For the majority (71.4%) of the drugs that were approved for adults in 2015, the pharmaceutical companies did conduct analyses on the effect of a patient’s weight on the pharmacotherapy. However, only 50% made that information readily available in their USPIs. This suggests that although various weight groups of adult patients (including obese patients) are studied within most of the clinical studies, the information is not always provided or communicated via publicly available sources. However, it must also be noted that this also may be due to the fact that none of the conducted analyses showed a clinically significant effect on the drugs’ pharmacokinetics and since the Code of Federal Regulations Title 21 Part 201 - Labeling by the FDA does not mandate the inclusion of obese patients within the section for “specific populations,” the sponsor companies may have chosen not to add the information to the labeling of the products. Sponsors should consider making this information available in USPIs, since over one-third of the US population is considered obese and treatment decisions require this knowledge.