Association of serious adverse events with type and sponsorship of clinical trials in patients with lymphoma

Abstract

6576 Background: Arguments have been made against early phase clinical trials (CTs) as possibly being unethical because its risk may outweigh its potential benefits. Whether this is true in the light of newer biological treatment for cancer is unknown. We therefore examined the association between the incidence of serious adverse events according to type and sponsorship of CTs in pts with lymphoma. Methods: All IRB approved CTs at the University of Nebraska Medical Center from Jan 2000-June 2005 classified as therapeutic for lymphoma involving a biological agent were included. CTs were classified in two ways: by type of CTs (phase I vs II vs III) and sponsorship (Investigator-initiated vs Industry-initiated. Multivariate logistic regression was used to evaluate the association between types/sponsorship of CTs with the incidence of IRB serious adverse events (SAE; no vs yes) and fatal adverse events (FAE; no vs yes) while adjusting for age, sex, race, lymphoma type and stage, interval from dx to tx, co-morbid conditions, and previous tx. Results: 357 pts with lymphoma enrolled in 29 CTs were included. The median age of pt was 54y (21–88). 41% of the pts had follicular lymphoma, 36% diffuse large cell, 14% mantle cell and 9% were other types. 59% had Stage IV lymphoma. 71% of the pts participated in investigator-initiated CTs, while 29% participated in industry-initiated CTs. 21% of pts were enrolled in phase I, 65% in phase II and 14% in phase III studies. SAEs were seen in 49 pts (14%), while FAEs occurred in 13 pts (4%). Multivariate analysis showed the risk of having SAE was independent of the type or sponsor of CTs. Additionally, the risk of FAEs was not associated with the type of CTs. However, the risk of having FAEs was less in investigator- iniatiated CTs than in industry-iniatiated trials (Odds Ratio: 0.13 (95% CI, 0.03–0.61, p = 0.01). Conclusions: Our study showed that in CTs involving biological treatments, the incidence of SAEs was not associated with the type or sponsor of CTs suggesting that use of biological agents in phase I studies may have similar risks to phase II/III trials. Further studies should be done in other types of malignancies to evaluate further the decrease frequency of FAEs seen in investigator-initiated trials. No significant financial relationships to disclose.