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Journal of Clinical Oncology, Vol 24, No 12 (April 20), 2006: pp. 1860-1867 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.03.8976 Factors Associated With Participation in Breast Cancer Treatment Clinical Trials
From the Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC; RTI International, Waltham; New England Research Institutes, Watertown, MA; and The University of Texas M.D. Anderson Cancer Center, Houston, TX. Address reprint requests to Nancy E. Avis, PhD, Department of Public Health Sciences, Section on Social Sciences and Health Policy, Wake Forest University School of Medicine, Piedmont Plaza II, Winston-Salem, NC 27157-1063; e-mail: navis{at}wfubmc.edu
PURPOSE: It is well established that recruitment to clinical trials (CTs) is difficult and time consuming. This article reports on factors related to CT participation among women who were invited to participate in a CT for breast cancer. PATIENTS AND METHODS: Breast cancer patients who were eligible for a CT were identified by 16 different cancer centers. After their invitation to participate in a trial, patients who were undecided about participation in a CT were recruited into the present study at that time. After a patient made a decision about trial participation, a telephone interview was conducted to assess knowledge of CTs, perceived benefits and drawbacks of CTs, and personal factors affecting the women's decision regarding participation. RESULTS: A total of 208 patients participated in the study. Fifty-eight percent of the patients decided to participate in a trial. Logistic regression analyses showed that the factors best explaining participation were trial phase, perceived drawbacks, time and travel considerations, therapeutic benefit of trial, and physician recommendation. Participation rates were similar for both phase I and phase III trials. However, a higher percentage of women recruited to phase II trials accepted. CONCLUSION: This study suggests that reducing drawbacks of CT participation, particularly travel time, and improving physician communication of trials are needed to increase trial participation.
As with most diseases, progress in treatment of breast cancer is best accomplished through well-designed, prospective clinical trials (CTs). However, patient accrual to CTs is a difficult problem.1-9 A review of 41 randomized CTs in the United States found that 34% of trials recruited less than 75% of their planned sample.8 It is generally found that only approximately 2% to 3% of adult cancer patients are entered onto CTs,10,11 whereas approximately 5% all of women with breast cancer participate in a CT.12 Although this low rate of participation is partly a function of lack of trial availability at any given time, an evaluation of National Cancer Institute–sponsored trials at 15 sites found that patient refusal accounted for the nonenrollment of nearly 40% of patients clinically eligible for a trial.9 Patient obstacles to participation in CTs include negative attitudes towards or beliefs about CTs,6,13-16 lack of knowledge or adequate information,14,16-18 concern about random assignment or wanting a specific treatment,8,19-24 inconvenience,6,8,25-27 possible risks or discomfort,25 and lack of family support.15,21 The analyses reported here further our understanding of trial participation among breast cancer patients by examining factors related to CT participation. Although numerous studies have examined factors related to CT participation in general, only a few focus specifically on breast cancer patients.17,20,28,29 In the present article, we compare women who agreed to participate in a CT with women who declined participation on a range of variables including sociodemographics, medical factors, trial type, knowledge about CTs, perceived benefits and barriers of CTs, and factors that affected one's personal decision regarding participation. The analyses are part of a larger study that was originally undertaken to compare the effectiveness of a novel videotape with a standard brochure for increasing participation in CTs. The videotape was designed to address two of the previously mentioned patient-related factors, specifically negative attitudes toward CTs and lack of knowledge about CTs. Previous analyses found no significant differences between the two education groups in terms of knowledge or attitudes toward CTs or trial participation.
Study Overview Potential study participants included all female breast cancer patients at participating institutions who were determined eligible to participate in a treatment CT for breast cancer and were undecided about participation in the CT. The focus was necessarily on undecided women because trial participation was a primary outcome. Patients were English or Spanish speaking and at least 18 years of age. A total of 16 different sites, including major cancer centers and Community Clinical Oncology Programs, participated in the study. Immediately after the invitation to participate in a CT, at the same clinic visit, patients were recruited onto the present study. Patients were told that the study was designed to test various educational materials about CTs and that they would be given some materials to review and later contacted for a telephone interview for which they would be paid $25. After obtaining informed consent for the study, patients were randomly assigned to one of two educational groups (either a booklet or videotape group) and given the educational materials to take home and keep. Random assignment to the videotape or booklet group was performed within site. After a patient made a decision regarding trial participation, the site notified the New England Research Institutes, where three authors (N.E.A., K.W.S., and C.L.L.) were affiliated at the time of the study. A follow-up telephone interview was arranged with the study participant. The telephone interview was designed to assess knowledge of CTs, perceived benefits and drawbacks of CTs, and factors affecting the women's personal decision regarding participation.
Intervention Materials
Measures Sociodemographic factors. Sociodemographic factors included age, level of education, race/ethnicity, employment status, income, health insurance, and insurance coverage of the CT. Medical factors. Medical factors included self-report of time since diagnosis, stage of breast cancer, type of surgery, type of treatment, and self-assessed health. Knowledge of CTs. A list of 22 items was developed to assess knowledge of CTs. Respondents rated each item on a 4-point scale (definitely true, probably true, probably false, or definitely false). Items were derived from information presented in the educational materials and were designed to assess a wide range of aspects of CTs. The items covered such topics as the purpose of CTs, random assignment, eligibility, participant rights, and informed consent. Items were pretested in an earlier phase of the study. A reliability analysis of the pretest data identified poorly performing items that were subsequently reworded or omitted. Attitudes toward CTs. Attitudes toward CTs were assessed with two separate scales. One scale asked about beliefs about the benefits of CTs, and the other scale asked about drawbacks. For both scales, respondents indicated how much each item was a benefit (or drawback) on a 5-point scale from "not at all a benefit" (or drawback) to "very much a benefit" (or drawback). Items were derived from the literature and an earlier pilot phase of the study of focus groups with breast cancer patients. The benefits scale consisted of seven statements that covered issues such as helping others, the opportunity for new treatments, and getting better medical care. The drawbacks scale consisted of 15 statements covering items related to privacy and confidentiality, adverse effects of treatment, feeling like a "guinea pig," time and inconvenience, and lack of trust in medical research. Factors in personal decision. Women rated how much each of nine items influenced their personal decision to participate in a CT. For each factor, women rated whether it was a factor strongly against their participation, somewhat against their participation, neither against nor in favor of their participation, somewhat in favor of their participation, or strongly in favor of their participation. Factors included items such as potential adverse effects of treatment, attitude toward random assignment, trust in medical research, amount of time and travel required, and recommendation of others (physician, family, and friends). Feelings about knowing about CTs. Davis et al30 previously evaluated the booklet by asking questions related to how knowing about CTs makes a person feel. Respondents were asked whether their understanding of CTs was clear or confusing and whether knowing about CTs made them feel upset or relieved and hopeful or doubtful. Davis et al30 found that, compared with a control group, the booklet group was more likely to feel clear in their understanding of CTs and more likely to feel relieved. These questions were also included in our interview.
Statistical Analyses Participation decision analysis. The influence of factors hypothesized to affect the decision to participate in the CT was estimated using logistic regression. The explanatory variables in the model consisted of variables of particular interest including scale scores for benefits, drawbacks, and knowledge; ratings of personal decision factors, race, intervention group status (video v booklet); and factors significant in bivariate analyses (clinical site and trial type).
Sample Characteristics Sites reported identifying 211 eligible patients and recruited a total of 208 patients to participate in the study. Of these patients, we were able to interview 191 women. Reasons for not obtaining a completed interview included deceased (n = 2), refused (n = 3), too ill (n = 2), ineligible (n = 1), unable to complete interview (n = 2), and unable to reach (n = 7). Of those women who were interviewed, eight were excluded from analyses because the trial was no longer available before they made a decision, thus producing an analytic sample of 183 women. Women were interviewed between 1 and 50 days after their decision (median, 13 days). Sociodemographic and medical characteristics of the patients are listed in Table 1. Women ranged in age from 30 to 83 years, with a mean age of 51.5 years (median, 51 years). The majority of women were white (77.1%) and worked full or part time (57.8%). Approximately half had a household income more than $50,000 per year, with 13% having an income of less than $20,000.
Time since diagnosis ranged from within the past month to 14 years (mean, 8 months; median, 1.7 months). The majority of respondents had stage II cancer, but 27.3% of patients did not know their stage. More than half of the patients (52.4%) reported having a mastectomy. The majority of women (82.5%) had had chemotherapy by the time they were interviewed, whereas fewer had radiation (10.4%) or hormone therapy (8.2%). Most women (78%) were being recruited for phase III trials. The majority of the respondents (68%) were from a single site (M.D. Anderson Cancer Center, Houston, TX).
Scale Reliability
Trial Participation: Bivariate Associations
As seen in Table 3, women who agreed to participate had significantly higher benefit scores (P = .0003) and lower drawback scores (P < .0001). They were also more likely to report that knowing about CTs made them feel relieved (P = .002) and hopeful (P = .005). There were no significant differences in age, time since diagnosis, or knowledge.
Beliefs About benefits and Drawbacks and Personal Decision
Figure 1 shows the mean response to the individual drawbacks. Ratings on most of the items were significantly different between accepters and decliners. The biggest drawbacks for both groups were undesirable adverse effects of treatment, potential for less effective treatment, experimental treatment too risky, and not knowing what to expect, although all of these factors were significantly greater for decliners. Factors that most differentiated accepters from decliners were transportation problems, disruption of daily routine, too much time, and don't know what to expect. Other significant factors were too much blood drawn, too many injections, lack of privacy, and possible change in relationship with health care provider.
The individual personal decision items show clear differences between accepters and decliners (Table 5). Accepters were more likely to rate benefit to others, potential therapeutic benefits, physician and family recommendation, and trust in medical research as factors in favor of their own decision to participate in the CT. Decliners were likely to report amount of time and travel, potential adverse effects, and attitude toward random assignment as the biggest factors against their own participation. For all personal decision factors, there were significant differences between accepters and decliners. Subsequent analyses by trial type showed that women recruited to phase III trials were more likely than women recruited to phase II trials to say that concern about potential adverse effects and amount of time and travel were factors against participation.
Logistic Regression of Trial Participation The logistic regression model included variables of theoretical interest in our model (knowledge, benefits, drawbacks, factors in personal decision, race, and educational group), as well as variables significant in bivariate analyses (trial type, site, feeling relieved, and feeling hopeful). The only significant variables were trial type (odds ratio [OR] = 6.44), drawbacks score (OR = 0.37), and two personal decision factors, time/travel (OR = 2.64) and physician recommendation (OR = 2.00; Table 6). Women recruited to phase II trials were more likely to participate, as were women with lower perceived drawbacks, women who saw physician recommendation as a factor in favor, and women for whom time/travel was less a factor against participation.
We next used backwards elimination to obtain a parsimonious model containing only statistically significant variables (model 2). Results are similar to model 1, with the addition of potential therapeutic benefits as a significant positive factor in trial participation.
It is well recognized that many oncology patients do not participate in CTs, and trial recruitment is often difficult and slow. In this study of patients being recruited to breast cancer treatment trials, we found that trial type, perceived drawbacks, time and travel, and physician recommendation best explained trial participation. Women recruited for phase II trials were much more likely to accept participation than women recruited for phase I or III trials. Potential adverse effects and amount of time and travel were greater factors against participation for women recruited to phase III trials. Random assignment may also be a major drawback for phase III trials,19,24,22 and phase II trials may also be seen as more cutting edge than phase III trials. Drawbacks, such as concerns about the treatment and time and travel, were also important factors. These factors have previously been found to be major barriers to trial participation.4,20,22,23,26,31-35 On the basis of the multivariate model, drawbacks were more important than benefits, which is consistent with another study that found that negative aspects of trial participation were more influential than perceptions about advantages.29 Although all physicians had invited women to participate in a trial, decliners were significantly less likely to view their physician recommendation as a factor in favor of participation. Either physician recommendation was less important to decliners or they viewed their physicians as less strongly in favor of participation. Other studies have also shown that physician willingness to refer a patient to a trial is one of the major factors affecting a patient's decision19,36 and that a patient's intentions are significantly related to the type of information physicians provide about CTs.37 Physicians have views about the value of particular trials for individual patients and may convey these either directly or indirectly to patients. Although several studies have focused on the physician's role in recruitment,28,37-40 more work is needed on how physicians and other health care professionals communicate CTs to patients. Knowledge about CTs was not related to participation. However, all study women received educational materials, and knowledge for both groups was high. This finding is consistent with the findings of Davis et al,30 who found that a booklet improved cancer patients' knowledge about CTs but did not affect recruitment. It is also consistent with research showing that knowledge is not sufficient to affect behavior29,41-43 and that interventions need to go beyond imparting knowledge. There are several implications of this study for the clinical oncologist and those who design CTs. First, to improve trial recruitment, trial logistics need to be easier for patients. Greater participation by community oncologists in CTs could help increase participation by reducing patient travel time. Reducing clinic visits, protocol burden, and other potential drawbacks may also help. Second, physicians may be unaware of how they present trial information to patients and need to be cognizant of their biases and how these influence patients. Third, future research on CT recruitment might focus primarily on phase III trials. There are several limitations of the present study. First, women who declined trial participation at the time of trial recruitment were not included in the study. Although this group was small (n = 5), their decision may be influenced by different factors compared with women more open to participation. Second, although the percentage of nonwhite women was higher than most other studies of breast cancer patients,20,28,44 the sample consisted of young, predominantly white women of higher education seeking treatment at a major cancer center. Thus, results cannot be generalized to all women being recruited for CTs. Despite this limitation, however, our results are remarkably consistent with those of other studies. In conclusion, this study suggests that additional interventions and strategies beyond imparting knowledge are needed to reduce trial drawbacks and increase participation. Physician recommendation is an important factor related to participation, and greater attention to this is needed in the recruitment process.
The authors indicated no potential conflicts of interest.
We would like to acknowledge the following cancer sites for their help in recruiting study participants: Central Illinois Community Clinical Oncology Program (CCOP) –Decatur Memorial Hospital, Dana-Farber Cancer Institute, Dayton Clinical Oncology Program, Greater Phoenix CCOP, Johns Hopkins University, Harbor View Cancer Center, M.D. Anderson Cancer Center, Merit Care Hospital CCOP, Montana Cancer Consortium CCOP, Northern New Jersey Cancer Center CCOP, Northwest CCOP, San Juan City Minority-Based CCOP, Southern Nevada Cancer Research Foundation CCOP, Sylvester Comprehensive Cancer Center, Union Memorial, University of Michigan Research Base, Upstate Carolina CCOP, and Washington Cancer Institute at Washington Hospital Center.
Supported by Grant No. R44 CA62793 from the National Cancer Institute. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
was computed as a measure of scale reliability. Scale scores were computed as the mean of the individual item scores; the knowledge score was a count of the number of items answered correctly (definitely or probably). 
2 = 13.93; P = .0009), with women being recruited to phase II trials being more likely to accept participation than women recruited to phase I or III trials. Site was significantly associated with participation, with women from M.D. Anderson Cancer Center more likely to decline (
