Post-approval drug problems could be due to poor adherence in trials, study finds

MCLEAN, Va. — Unexpected toxicities from prescription drugs that emerge years after regulatory approval may be due to poor medication adherence in clinical trials, according to a new study.

While much attention on medication adherence has focused on patients not taking the already approved drugs prescribed to them or not taking them properly, the new study, released Tuesday by Consumer Health Information, found problems with adherence in clinical trials as well.

"Patient adherence in clinical trials must always be higher than that of the general population," Consumer Health Information president and CEO Dorothy Smith said. "Our challenge is to get patient adherence in clinical trials up to 95% so patients can be assured it is safe to take the FDA-approved dose."

According to the study, which looked at data from over the past 20 years, patient adherence wasn't monitored between 1997 and 1999 in 53% of clinical trials of drugs that are still on the market today. Meanwhile, up to 30% of study patents did not take the full dosage, and patients could not understand 35% to 94% of informed consent documents. At least half of patients didn't tell the study team that they had missed doses, and many did not realize that missing doses could endanger the lives of millions of people after a drug's approval because undetected poor adherence could result in inaccurate dosing.

Smith recommended that clinical trial investigators develop adherence strategies and integrate behavior modification; determine how many doses of each drug can be missed without jeopardizing the therapeutic outcome; include patient adherence results as an outcome of the clinical trial and publish it in the package insert; create informed consent and patient-friendly programs that patients will understand; and gain patient trust so they provide honest feedback about any problems they have.

Unexpected toxicities have resulted in the FDA cutting drug dosages and withdrawing approval for others, but may be occurring because patients in the general population are more adherent than those in the clinical trials.

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