Abstract
Background and Purpose:
Clinical trials on HSCT differ from those on conventional chemotherapy, which focus on a single drug, with regard to the inevitable combined use of multiple anticancer drugs in preparative regimens, and the variety of medications required for intensive supportive therapies. This makes the collection and analysis of data regarding adverse events and concomitant drugs, quite labor- and cost-intensive. Moreover, quality assurance and quality control practices to assure the reliability of the obtained data can be very difficult. Nevertheless, safety data handling procedures have not yet been validated in the field of HSCT. Thus, we examined the feasibility of current maneuvers in correlation with the clinical outcome in an autologous setting.
Methods:
In 41 patients with NHL who had bone marrow infiltration and who received autologous HSCT in 12 institutes between 1999 and 2002, all adverse events and information regarding concomitantly used drugs were analyzed.
Results:
Over a median follow-up of 90 days, 1,506 adverse events (37 events/person) were observed, and 3,426 concomitant drugs (84 drugs/person) were used. Ninety-one percent of the adverse events occurred in the early phase of transplantation (< day 30), with 80% caused by regimen-related toxicities (RRT), which was considered to be a characteristic of HSCT compared to conventional chemotherapy. The severity scores of adverse events were 46%, 23%, 17%, and 13%, for NCI-CTC grade I, II, III, and IV, respectively. No particular procedure or treatment was required for 65% of the grade I adverse events, and none progressed to more severe problems or patient death. Moreover, we found that the decision to report or not totally depended upon the widely variable individualized assessment by physicians, which makes reliable statistical analysis meaningless. Sixty-four percent of the concomitantly used drugs (2,204 of 3,426) were related to the treatment of RRT, and 51% (1,121 of 2,204) were used for prophylaxis of RRT. Moreover, 59% (2,007 of 3,426) were used in patients who had no adverse events: 20% of these (402/2,007) were over-the-counter drugs, and 16% (322/2,007) were inactive, such as injection solvents and iv solutions used simply to keep the line open, etc. These findings highlight the characteristics of HSCT compared to conventional chemotherapy.
Conclusion:
These findings clearly show the urgent need for a more efficient yet reliable data collection system in clinical trials of HSCT. We suggest that this can be accomplished by excluding the handling of grade I adverse events without the need of treatment and the less-significant information about concomitant drugs. In this study, we estimated that such modification would reduce the number of reported adverse events to 70% (1,055/1,506) and that of concomitant drugs to 78% (2,702/3,426). Hence, substantial reductions in cost and labor can be expected in clinical trials, with a greater focus on reliable safety assessment.
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