Since the 2004 literature review assessing clinical trial subjects’ understanding of informed consent (Flory & Emanuel, 2004
), little has been published to rigorously test interventions to improve actual understanding of the eight basic elements of informed consent stated in the U.S. federal regulations (DHHS, 2009
). While the AACTG and other HIV clinical trial networks do incorporate assessments of understanding in their informed consent procedures, this pilot study is a first step in helping to improve actual informed consent understanding of the eight basic elements of informed consent among AACTG enrollees. Several contributions can be noted.
First, the study developed and evaluated an adapted version of the QuIC instrument (Joffe et al., 2001
) to assess the eight basic elements of informed consent, rather than developing an original instrument that assesses rote memorization of specifics on any given AACTG protocol. This not only facilitates cross-trial site comparisons within the AACTG, but also can help AACTG researchers within a trial site identify aspects of the informed consent that their enrollees are not understanding, and educate enrollees on those particular elements. For example, our findings demonstrated that items measuring purpose and subjects expected participation, risks, alternatives to participation, confidentiality of data, injuries associated with greater than minimal risk research, and voluntariness of consent to research may not have been discussed with, or were confusing to AACTG enrollees at the time of the baseline assessment. With targeted education, the intervention group improved their understanding of these elements of informed consent. Two of the items measured—The treatment being researched in my clinical trial has been proven to be the best treatment
, and Compared with standard treatments, my clinical trial does not carry any additional risks or discomforts
—are related to the therapeutic misconception often associated in clinical trials where subjects misunderstand the clinical trial as being therapeutic (Miller, 2008
). Indeed, these two items also were incorrectly answered in the original QuIC study (Joffe et al., 2001
), demonstrating that these items may be difficult to understand across clinical trials regardless of the disease.
Lastly, the pilot study used a randomized controlled study design to test a targeted, educational intervention to improve actual understanding of the basic elements of informed consent. This contribution responds to Flory’s and Emanuel’s (2004)
recommendations to employ rigorous methods to test an intervention, and to focus on interventions that emphasize in-person discussions since other informed consent interventions (e.g., focus on simplifying or shortening the consent form, and/or video/multi-media interventions) did not demonstrate effectiveness to improve informed consent understanding (actual or perceived). This study demonstrated a statistically significant intervention effect, with a 3-point difference for follow-up versus baseline of the intervention and control groups. The targeted educational intervention also has the advantage of being brief, and along with administering the adapted QuIC instrument, could be feasible to do as part of any informed consent process undertaken by an AACTG trial site. This would be our recommendation to AACTG sites that would be interested in implementing initial informed consent education and assessment to their recruitment process, and/or periodic monitoring to ensure comprehension throughout the course of a clinical trial.
This pilot study does have some limitations that should be noted. The primary limitations have to do with sample size and recruitment. We did not meet our intended sample size goal, mainly because our subjects represented only 3 of 5 AACTG protocols from which we were allowed to recruit, and at the time of our study, these protocols’ recruitment efforts were either winding down, or these protocols were recruiting 1–2 individuals per month. Second, we also were concerned with the possibility of selection bias, given that we were dependent on the AACTG site’s study coordinators letting us know which subjects we could ask to participate in our study. We expect this is the reason why all of the subjects who we were allowed to approach agreed to participate in our pilot study. To minimize selection bias, the ideal recruitment scenario for our study would have been that we could ask all newly enrolled AACTG subjects to participate in our study to assess both refusal and participation rates, and to possibly collect demographics data for the refusals. Despite not being able to meet our intended sample size, and problems with our recruitment process, we were able to minimize selection bias with very low loss to follow-up, as well as demonstrate effectiveness of the targeted educational intervention. A third limitation is that our pilot study subjects represented one U.S. AACTG site, HIV-infected adults, and enrollees in therapeutic
HIV/AIDS trials, thus decreasing generalizability to pediatric AIDS clinical trials, international AACTG sites and possibly other U.S. AACTG sites, and HIV prevention trials that may include non HIV-infected individuals. One final limitation relates to whether using forced-choice checklists, like our adapted QuIC instrument, really measures actual understanding of informed consent, based on a 2006 published study that compared methods of assessing actual understanding of informed consent in HIV vaccine trials (Lindegger et al., 2006
). Based on our findings, we do agree with the authors that forced-choice checklists may overestimate actual understanding, and used alone, will not help study participants understand the basic concepts of informed consent. While our targeted educational intervention did not use open-ended narratives and vignettes, as the Lindegger et al. (2006)
study recommended, we do believe that targeted education does allow for open-ended discussion of the basic elements of informed consent, and is a more feasible option for AACTGs to incorporate into their informed consent process since it would not require additional resources to collect and analyze the open-ended (qualitative) data.
In conclusion, the informed consent process in AIDS clinical trials has not always been successful in communicating to new enrollees the eight basic elements of informed consent stated in the U.S. federal regulations. Learning these elements could be useful to enrollees to better understand the clinical trial itself and their expected participation. Monitoring consent in such a manner would ensure not only a signed agreement between researchers and subjects, but also uphold the underlying assumption that subjects understand the content of the consent form throughout the course of an AIDS clinical trial.