Sources and handling of losses to follow-up in parallel-group randomized clinical trials in dogs and cats: 63 trials (2000-2005).

Abstract

OBJECTIVE: To determine the sources and handlingof losses to follow-up (LTF) in parallel-group randomized clinical trials (RCTs). SAMPLE POPULATION: 63 parallel-group RCTs of > 24 hours' duration published from January 2000 through December 2005. PROCEDURES: Journals were hand searched for eligible reports. Details concerning the presence, cause, and amount of LTF; statistical handlingof data missingbecause of LTF; type of analyses performed; number of animals randomly allocated and analyzed; and the acknowledgement of the potential impact of LTF were recorded. RESULTS In 81% (51/63) of trials, LTF were reported. In 80% (41/51) of those studies, losses in the analysis were ignored, and in only 18% (9/51) was the potential impact of LTF on study results acknowledged. Of the 47 studies in which sources of LTF were reported, 72% had loss of subjects because of investigator withdrawals, 30% because of deaths, and 26% because of owner withdrawals. Median loss of subjects for those studies was 12% because of investigator withdrawal (range, 2% to 52%), 8% because of death (1% to 28%), and 4% because of owner withdrawal (2% to 33%). CONCLUSIONS AND CLINICAL RELEVANCE: Most RCTs had LTF, most of which were attributable to investigators removing randomly allocated animals from the study. In most studies, data from animal LTF were ignored and, therefore, only a subgroup of randomly allocated subjects was included in the data analysis. Most reports did not address the potential for a postrandomization selection bias associated with ignoring LTF and did not acknowledge the potential impact of the missingdata on their results.