Context Use of experimental therapies during but outside of randomized controlled
trials (RCTs) has not been studied.
Objective To determine whether initiation of an RCT leads to increased use of
the experimental therapy outside the trial.
Design and Setting Data on national apheresis use during 3 Canadian RCTs for multiple sclerosis
(1986-1988), thrombotic thrombocytopenic purpura (1982-1988), and myeloma
cast nephropathy (1998-2000) were obtained from 19 major medical centers in
Canada. The multiple sclerosis and myeloma cast nephropathy trials had data
on apheresis use for 3 years prior to and during the trials, which permitted
a time-series analysis to determine the impact of the RCTs on the use of apheresis.
The ongoing myeloma cast nephropathy trial provided data on the number of
patients inside and outside of the RCTs in trial and nontrial centers. Initial
and follow-up questionnaires were sent to 24 Canadian physicians in trial
and nontrial centers to determine if they had noted an increase in apheresis
activity during the trials and, if so, their explanation for it.
Main Outcome Measure Change in number of patients undergoing apheresis for thrombotic thrombocytopenic
purpura, multiple sclerosis, and myeloma cast nephropathy prior to and during
the respective RCTs compared with all patients undergoing apheresis during
the same periods.
Results During all 3 RCTs, there were large increases in use of apheresis. The
majority of the increased use of apheresis was outside of the trials: for
multiple sclerosis, 30 of 49 patients per year (61% of increase); thrombotic
thrombocytopenic purpura, 49 of 56 patients per year (72% of increase); and
myeloma cast nephropathy, 60 of 72 patients per year (57% of increase). The
myeloma cast nephropathy study noted that this increase occurred in both nontrial
and trial centers. Among questionnaire respondents (n = 22; 92% response rate),
most physicians noted an increase in apheresis activity during the trials
and attributed it to a "jumping-the-gun" phenomenon.
Conclusions During 3 Canadian RCTs, apheresis increased, but most of the increase
occurred outside the trials. This behavior during an RCT, in the absence of
clear efficacy, can be termed jumping the gun.