The impact of patient, institutional, and study factors on cancer clinical trial accrual has been examined extensively, but few studies have investigated whether patient interest and participation in clinical research vary by aspects of the research consent process. In this study of patients enrolled in a cancer center tissue repository, we focused on two such potentially modifiable factors: consenter experience and timing of consent. We found that consenter experience was significantly associated with and timing of consent had a clear trend toward association with markers of patient interest in research.
We categorized consenter experience according to the number of participants enrolled in the tissue repository by an individual consenter. Among patients enrolled by first-time consenters, 76% agreed to be contacted in the future to participate in other research studies, compared with 84% of patients who were the second or third participant enrolled by an individual consenter, and 88% of patients who were the tenth or later participant (P = .002). Considered conversely, the proportion of patients declining future contact went from 24% to 12%, a 50% relative decrease.
These results build on our previous work, in which we found that participants enrolled by high-volume consenters were more likely to agree to be contacted for medical follow-up and future research studies.13
In that study, participants consented at any point by study personnel who ultimately enrolled more than the median number of participants per consenter (ie, eight) were more willing to be contacted for future research. With this earlier approach, however, many participants enrolled by an experienced consenter were enrolled at a point when that consenter was not yet experienced, suggesting that other consenter characteristics—such as interest in and enthusiasm for the study—may have contributed to participant response. By examining the specific order in which a patient was enrolled by an individual consenter, the present study provides a more clinically relevant and applicable measure of consenter experience.
Along these lines, prior research has suggested that a supportive and clear physician communication style is associated with patient and family interest in clinical research.14
It has also been shown that direct interaction between study personnel and participants is the most effective means of improving participants' understanding of information disclosed in the informed consent process.15
Other studies have demonstrated that interventions such as workshops and videos can improve research personnel communication skills16–19
and quality of informed consent20
in cancer clinical trials. In the present study, however, consenter experience more likely reflected familiarity with study-specific content and documents than it did general communication skills. First, our data do not account for consenter experience with other research protocols. For some consenters, the first participant enrolled in the tissue resource may have been the first participant he or she enrolled on any research study, whereas others may have participated in numerous prior clinical trials. Second, it is unlikely that consenters' general communication styles would have changed significantly after enrollment of a single participant in the tissue resource.
As clinical research becomes more complex, this ability of research personnel to understand and explain study-specific details and consent documents is likely to become even more important. Over time, consent forms have become longer21,22
and more difficult to comprehend.23,24
The consent form for the UT Southwestern Tissue Resource, the basis of the present study, provides a relevant example. Although study procedures are straightforward—namely, the procurement and storage of clinical information and excess tissue from a procedure performed as standard clinical care—the six-page document covers such complex concepts as compensation for injury, compensation for future commercial developments, and the definition, processing, and storage of DNA.
We also evaluated the timing between diagnosis and invitation to participate in the research study—a factor in the research consent process that has not, to our knowledge, been evaluated previously. Willingness to be contacted for medical follow-up and future research studies was greatest among those patients enrolled between 1 and 30 days after disease diagnosis. A potential explanation is that this interval features less uncertainty and anxiety than the prediagnosis period, during which patients may be more focused on the risks and results of the upcoming diagnostic procedure than on the possibility of future research participation. Furthermore, the early interval after diagnosis is established may represent the height of patients' interest in their disease and treatment, as evidenced by a consistent and significant decline in willingness to be contacted for medical follow-up and future research among patients consented after this period. This observation has particular relevance to those clinical trials, such as secondary prevention studies, that require a waiting period of several months after initial cancer diagnosis and treatment before enrollment.
In this study, patient characteristics predicted responses to a lesser degree than did factors related to the consent process. Willingness to be contacted for medical follow-up and future research was not associated with sex (P
= .19 and P
= .31, respectively) or race (P
= .83 and P
= .40, respectively). Numerous studies have demonstrated racial disparities in clinical trial accrual7–9
; our results suggest that these differences may in part reflect access to trials or reservations about specific study procedures,25
rather than a general aversion to clinical research. Consistent with previous reports,26,27
older patients in this cohort seemed less willing to be recruited for future research studies.
This study has a number of limitations. Foremost among them is the nature of the primary end point. It is not known if willingness to be contacted for future research opportunities correlates with willingness to participate in research, whether therapeutic or observational. Agreeing to be contacted for future research opportunities is clearly not equivalent to enrolling onto a clinical trial. The former entails minimal commitment or risk, whereas the latter may directly affect treatment selection, toxicities, and clinical outcomes. Nevertheless, patient willingness to consider clinical research represents a critical element of study accrual. We also believe this end point to be more interpretable than clinical trial enrollment, which depends not only on patient preference, but also on external factors such as study eligibility and availability. Although statistically significant, the different results between less and more experienced consenters may on initial consideration seem not clinically meaningful. Indeed, additional experience yielded a relative increase in “yes” responses of only 16%. This result reflects the high baseline rate of agreement to be contacted for future research, which leaves little room for improvement. However, applying the 50% relative decrease in “no” responses we observed to a hypothetical but plausible research scenario in which—perhaps because of difficulties in understanding more complex study content and procedures—a smaller proportion of potential participants agree to participate at baseline, the effects could be substantial.
In addition, aspects of the study population may limit the generalizability of our findings. In our study setting—an academic medical center—patients, staff, and clinicians may have research interests and motivations distinct from those encountered in community practices. This setting may also account for the atypically young age of the study sample (75% ≤ age 65 years), which in turn could bias our results. The 17% of participants who had either benign disease or were healthy controls may have skewed our findings, although disease status was not significantly associated with participant responses in univariate analysis. Finally, the study cohort included only those patients who agreed to participate in the UT Southwestern Tissue Resource. We have no information on those who were never approached to participate in the tissue resource and only limited information on those who were approached but declined. However, we believe our cohort is at least as representative a patient sample as those included in survey- or questionnaire-based studies, in which response rates are generally only 20% to 30%,28,29
and participants may be particularly motivated and interested in research. By contrast, because the UT Southwestern Tissue Resource entails little risk or time commitment, the overwhelming majority of those approached agree to participate. As a result of our interest in this issue, the UT Southwestern Tissue Resource recently started recording these figures; since that time, 514 (92%) of 556 individuals approached have agreed to enroll.
In conclusion, this study demonstrates that factors related to the consent process may affect patient interest in and willingness to consider participation in clinical research. To our knowledge, this is the first study to evaluate these variables quantitatively. Specifically, we found that consenter experience was significantly associated with and timing of consent had a trend toward association with markers of patient interest in research. Consenter experience may be gained as early as the first consenting effort for a particular trial. This experience seems to be study specific and likely reflects familiarity with study procedures and documents. Patients seem most open to the possibility of clinical research shortly after diagnosis, specifically within 30 days. One possible explanation is that before diagnosis, patients are preoccupied by anxiety related to the risks and results of upcoming procedures; as time elapses after diagnosis, patients' interest in their disease and treatment may wane. Patient characteristics including sex, race, and diagnosis were not associated with research interest. Importantly, in this study, the variables most strongly associated with markers of patient interest and potential participation in clinical research—namely, consenter experience and the timing of study enrollment—are readily defined and potentially modifiable. Further study of these factors may improve efforts to increase cancer clinical trial accrual.