Easy-to-Read Informed Consent (ETRIC) Form for Hematopoietic Cell Transplantation (HCT) Clinical Trials: Results from Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1205 Study

The informed consent process, which allows potential participants to balance benefits and risks in making an informed decision about participation, is an essential aspect of conducting ethical clinical trials. Due to the complexity of HCT trial treatments, informed consent forms are often long and difficult to read, raising concern about compromise of the informed consent process. Whether enhancing the format of consent forms improves comprehension among HCT candidates participating in multicenter trials has not previously been investigated. The BMT CTN proposed a two-column ETRIC form incorporating evidence-based recommendations for health literacy, readability and plain language (Denzen et al, BBMT 2012). The BMT CTN 1205 study: (1) tested the efficacy of the ETRIC form in increasing comprehension of BMT CTN clinical trials, and (2) evaluated barriers and facilitators to its use at BMT CTN centers. The randomized study enrolled 198 patients at 25 centers participating in BMT CTN 0901, 1101, 1203, 1301 (parent) protocols (available at www.bmtctn.net). Adult patients (≥18 years) potentially eligible to participate in a parent trial, fluent in English, and providing consent were randomized to receive the ETRIC or standard consent form for that parent trial. Both forms were written at the 8^th grade or lower reading level; the ETRIC form included additional formatting enhancements intended to improve readability. The primary endpoint was objective comprehension score on the Quality of Informed Consent Part-A (QuIC-A) instrument; the study was powered to detect a 4-point difference in mean scores between the study arms assuming a 25% dropout between enrollment and assessment completion. Secondary endpoints evaluated subjective comprehension, anxiety, satisfaction, information location and consent rates. One hundred sixty-three (82%) patients completed any assessments after consent discussion for the parent trial and 152 (77%) were evaluable for the primary endpoint. Patient demographics including annual household income, education level and health literacy scores were balanced between the two arms. Mean (±SD) QuIC-A scores were comparable between the two arms (80.5±8.7 ETRIC form, 81.8±9.5 standard form, P=0.37). In regression analysis that adjusted for the effects of potential confounders, there was no significant association between the consent type and the QuIC-A score (P=0.57). There were no significant differences in subjective comprehension scores, anxiety related to consent process, satisfaction with the consent process, information location times and consent rates on parent clinical trials. There were no significant interactions between the consent type and age, household income, education level, health literacy scores or parent trial protocol. In the parallel evaluation study, two trained moderators conducted semi-structured interviews of 49 site investigators, research staff, IRB members and legal/regulatory staff at 9 BMT CTN transplant centers to understand barriers and facilitators to implementation of the ETRIC form. Sequential, transcript-based qualitative analysis was performed by two experienced coders using NVivo 10 software. Inter-coder agreement was high (kappa=0.90). Several dominant themes were identified; there was general comfort and willingness to utilize the ETRIC template and interviewees suggested that formatting and layout enhancements of the ETRIC form would offer additional value to research participants, investigators and IRBs. Several perceived barriers to local implementation were identified including center IRB/legal language preferences and requirements, length, and prior experience with alternative consent formats. A need for educational resources for researchers, staff and IRB members for implementing the ETRIC form was also identified. In conclusion, the formatting enhancements of the ETRIC form did not alter comprehension, anxiety, satisfaction, information location or consent rates for BMT CTN clinical trials. Despite local challenges to implementation, BMT CTN center investigators, research staff and IRBs generally viewed the ETRIC form favorably, were comfortable using it, were pleased to have a resource that is 'easy-to-read', and expressed a willingness to utilize ETRIC over standard consent form.