Clinical Trials Need Greater Representation of Obese Patients, Experts Say
Obesity’s impact on drug pharmacokinetics and the prevalence of the disorder and its associated comorbidities warrant greater inclusion of obese patients in clinical trials, experts say in a recent opinion piece, yet this group too often goes unconsidered and unevaluated.
The literature shows that lipophilicity, or fat solubleness, plays a part in how drugs move through the human body; this means that fat soluble drugs may distribute themselves differently in patients with excess body fat (obesity) compared to drugs that are not fat soluble, Christina Chow, head of research at Emerald Lake Safety, David Greenblatt, professor at Tufts University School of Medicine, and William Dietz, director of the STOP Obesity Alliance, write in Health Affairs.
On top of this, the increased absorption of lipophilic drugs by body fat extends their half-life due to the drug’s ongoing release from fat tissue after the drug’s discontinuation, raising risks of unintended drug-drug interactions, such as excessive drug effects and adverse reactions, they say.
There are no FDA requirements to assess drugs specifically in obese patients, Chow, Greenblatt and Dietz say, despite increased body fat’s potential to alter the effects of drugs frequently used for treating obesity comorbidities and a lack of testing on obese patients for a number of lipophilic drugs commonly prescribed for obesity-associated comorbidities.
“Pharmaceutical companies are not required to include people with obesity in clinical studies, and the FDA has recognized that people with obesity are often excluded in an effort to reduce the variability in the effects of a drug,” they wrote. “Understanding such variability is critical to assessing drug safety and effectiveness in people with obesity. More broadly, the safety and effectiveness of treatment for the comorbidities of obesity have been understudied or ignored.”
The authors call on the FDA to take a number of actions to address this issue:
- Require drug companies to update the dosing instructions for certain drugs to avoid underdosing in obese patients, including atorvastatin, metoprolol, omeprazole, sertraline, alprazolam and ibuprofen, among others;
- Update clinical trial guidances and GCP regulations to direct sponsors to identify drugs that may have altered pharmacokinetics in obese patients, with language that specifically advises on how/when to include obese patients in trials and how to analyze and report the need for differences in drug dosages; and
- Establish a reporting system for drug metabolism-related adverse events in obese patients.
“Because many commonly prescribed drugs such as statins, beta blockers, antidepressants and atypical antipsychotics are highly lipophilic and commonly used in patients with obesity, studies must be done in people with obesity to assess the drugs’ clinical impact. The lack of such information reflects a failure of related regulatory and policy programs,” they say. “Regulators and policymakers can and should act now to address those failures, reduce uncertainty, protect patients and improve health.”
Read the full opinion piece here.