Major features of dose omissions in 87 ambulatory drug trials

Background From clinical studies whose sponsors have concurred with entering their anonymized data into a common archive, we have just finished the assembly and begun the analysis of data on15214 ambulatory patients whose dosing histories during studies of varying lengths have been electronically compiled. Methods Electronic Medication Event Monitors were used to record the times and dates of package entry during the course of 87 drug studies performed between 1990 and 2004. Chapter headings in the British National Formulary served to categorize fields of treatment. Results Study durations ranged from 30 to 1400 days. Patterns of deviation from prescribed dosing regimens varied widely, but were almost entirely markedly skewed toward longer dosing intervals than prescribed, i.e. under‐dosing, in every field of treatment. With QD[BID] regimens, 23%[45%] of doses were not taken on schedule. Drug holidays (3 or more days' lapse in dosing) occurred at least once in 21% of patients. This percentage doubled among patients followed for at least 6 months. In studies continuing beyond 6[12] months, almost 30%[40%] of trial participants had stopped taking the trial medication. Conclusions Underdosing, drug holidays, and early cessation of dosing are common features of clinical trials, and likely are frequent sources of low response and high variability in response to the protocol‐specified dosing regimen. These dosing errors are usually grossly underestimated by counting returned, untaken dosage forms. Clinical Pharmacology & Therapeutics (2005) 77 , P99–P99; doi: 10.1016/j.clpt.2005.01.006