A SPE is a mechanism that allows for a one-time, one-patient enrollment exception to an already approved study protocol. While SPE requests are intended to be rare, little is known about the number, frequency, and the specific rationale. To better define the nature of SPE requests, this study seeks to formally characterize our institutional experience with SPEs.
All SPE requests from April 2014 to January 2015 were generated through the Committee on Human Research (CHR)-iRIS database. Clinical trials associated with the SPEs were determined to be either oncologic or non-oncologic, and were categorized based on trial type and funding sources (i.e., investigator-initiated/industry unfunded, investigator-initiated/industry funded, industry-sponsored, cooperative group, and departmental). Moreover, all SPEs were evaluated for sponsor approval letter submissions and subsequent protocol amendments. Based on the written rationale given on the proposed modifications, the SPEs were grouped by rationale type and classified as having occurred pre-trial, mid-trial, or post-trial (i.e., before subject enrollment, after subject enrollment, or after treatment respectively).
Of the 125 SPEs identified, 122 were approved (97.6%), two were withdrawn (8%), one was returned for correction (0.8%), and zero were not approved (0%). Ninety sponsor approval letters were submitted (72%), and only 15 SPEs were followed by protocol amendments (12%). With respect to the clinical trial type and funding sources associated with the SPEs, 38 were investigator-initiated/industry unfunded (30.4%), seven investigator-initiated/industry funded (5.6%), 66 industry-sponsored (52.8%), 12 cooperative group studies (9.6%), and two were departmental (1.6%). Sixty-four SPEs occurred pre-trial (51.2%), 56 mid-trial (44.8%), and five post-trial (4%). Inclusion/exclusion criteria violations regarding disease status (n=33, 26.4%) and changes in treatment monitoring (n=28, 22.4%), and treatment scheduling (n=17, 13.6%) were the three most common reasons for SPE requests. Interestingly, 25 unique studies (29.4%) accounted for 65 SPEs (52%), highlighting the frequent occurrence of multiple SPEs per study. Of the 72 cancer clinical trials (57.6%), gastrointestinal oncology (n=19, 26.4%), genitourinary oncology (n=10, 13.9%), and any solid tumor (n=10, 13.9%) represented the majority of the cancer SPE distribution. In contrast, neurology (n=14, 26.4%), gastroenterology (n=8, 15.1%), and psychiatry (n=7, 13.2%) contributed to the majority of the non-cancer SPE distribution.
Almost all SPEs at our institution are approved. The majority of SPEs from April 2014 to January 2015 occurred pre-trial and originated from industry-sponsored cancer clinical trials. Review of the necessity, administrative burden, and effect on data integrity of this practice will motivate future studies.