- Top of page
- Materials and methods
Abstract. Madsen SM, Mirza MR, Holm S, Hilsted KL, Kampmann K, Riis P (Copenhagen University Hospital in Herlev, Herlev, Denmark; Odense University Hospital in Odense, Odense C, Denmark; University of Manchester, Manchester, UK; Copenhagen University Hospital in Herlev, Herlev, Denmark; and Odense University Hospital in Odense, Odense C, Denmark). Attitudes towards clinical research amongst participants and nonparticipants. J Intern Med 2002; 251: 156–168.
Objectives. To investigate attitudes to clinical research amongst cancer trial participants and nonparticipants, and to compare results with those from previous studies amongst participants in noncancer trials.
Design. Trial participating respondents were given three questionnaires during the clinical trials. Respondents amongst patients declining randomization answered a single questionnaire.
Setting. Participants and nonparticipants in randomized clinical cancer trials.
Subjects. Forty-one participants and 47 nonparticipants in cancer trials.
Results. Altruistic motives of physicians to conduct medical research were highly rated. Attitudes towards clinical research were positive in all groups, with nonparticipant respondents being the least positive. Eight to nine tenths found scientific testing necessary before general health service implementation. Trial participants were, as compared with nonparticipating respondents, more positive towards both participation of self and others. Both personal and altruistic motives for participation were highly rated. Primary reasons for nonparticipation were fear of ‘the unknown’ and/or unease with randomization. Only a minority felt a moral problem created by declining trial participation. Respondents amongst noncancer participants were more satisfied with the information given than both cancer participants and cancer nonparticipants. Negative experiences in cancer participants generally dealt with frustration related to seeing too many physicians at check-up appointments.
Conclusion. Attitudes towards clinical research are generally positive even in cancer nonparticipants. Both personal and altruistic motives for participation were highly rated. A fear of ‘the unknown’ and resentments towards randomization were primary reasons to renounce participation. Seeing too many physicians at check-up appointments seems to be an important factor for negative experiences in cancer trial participants.
Materials and methods
- Top of page
- Materials and methods
All patients found eligible to participate in the clinical cancer trials were also eligible to participate in the questionnaire study. Questionnaires were given at the first visit after the patient’s decision whether to be randomized or not to 41 patients accepting and 47 patients declining randomization. Only six of the approached patients declined to participate in the questionnaire study (7%). Further, questionnaires were handed out to cancer trial participants during the course and after completion of the trial. Distributions of cancer disease, sex and age are shown in Table 1. In the breast cancer group only premenopausal patients were included, as the protocol for postmenopausal patients did not include chemotherapy but endocrine therapy. The study was performed at the oncological departments in Herlev University Hospital and Odense University Hospital during 1997–1999.
Table 1. Number of respondents, sex and age distribution amongst respondents in questionnaire survey
The initial questionnaire probed attitudes towards aspects of clinical trials including reasons for participation and nonparticipation. In addition, the respondents were asked to evaluate the information they had received about the clinical cancer trial earlier. The questionnaires given during, and after the completion of the trial included questions about perceived satisfaction with participation. Most questions were on a multiple-choice form, with an additional space for free text. Comparisons between groups were only made, when questions were phrased identically.
All patients gave both verbal and written informed consent. The survey fulfilled the demands of Danish law and the Helsinki Declaration, and was approved by the Research Ethics Committee of Copenhagen County and the Scientific Ethical Committee for Vejle and Funen Counties (reg. no. KA 95059).
Previous questionnaire studies amongst noncancer trial participants  were performed amongst patients with inflammatory bowel disease (IBD) participating in one of two clinical studies (IBD-participants). One study was an open-labelled, randomized study comparing treatment of active left-sided ulcerative colitis with either self-administered subcutaneous injections of interferon-α-2a (Roceron®, Roche Inc., Hvidovre, Denmark) or prednisolone enemas (Predniment®, Ferring Inc, Hørsholm, Denmark). Thirty-two patients were randomized , and all completed the questionnaires given (Table 1). The other clinical study evaluated low-field magnetic resonance imaging (MRI) in active inflammatory bowel disease. Forty-seven patients participated , and all completed the questionnaires given (Table 1).
Nonparametric statistical tests (Kruskall–Wallis tests, Mann–Whitney tests) with a significance level of 0.05 were performed using the GraphPad Prism program version 3.00 for Windows (GraphPad Software, San Diego, CA, USA). All P-values are given as two-tailed. To examine a possible influence of sex and age of respondents on results a multinominal logistic regression analysis was performed using the SPSS statistical package version 10.1 for Windows (SPSS Inc., Chicago, IL, USA). For each dependent variable the analysis was performed with group, sex and age as independent variables. In performing the regression analysis age was categorized into three age-groups, age 0–35 years, 36–50 years, and older than 50 (Table 1).
- Top of page
- Materials and methods
The response rate of the initial questionnaire was very high, whereas the second and third questionnaires in the group of cancer trial participants were only answered by less than half of the respondents. The results concerning the latter two must therefore be interpreted with caution, as a considerable risk of bias is present.
In a previous questionnaire study in the healthy Danish background population exploring the same issues  we found women younger than 46 years having a less positive general attitude towards trials [95% CI’s of scores (same scale as in Table 3): age ≤ 46 years, 2.67–2.96; age > 46 years, 2.45–2.65; P=0.008). The younger women rated both a wish to get access to the new drug (95% CI’s of scores: age ≤ 46 years, 1.88–2.67; age > 46 years, 1.72–1.91; P=0.03) and a wish to obtain a good relation to the department performing the study (95% CI’s of scores: age ≤ 46 years, 2.81–3.24; age > 46 years, 2.34–2.64; P=0.0004) less important than the remaining respondents as motives to trial participation. Because of the inclusion bias introduced by only including premenopausal breast cancer patients, the present study in particular solicited the opinions of younger women, who thus could be expected to have a relatively critical approach towards clinical research. However, the multinominal regression analysis performed showed only very few items being influenced by age and none by sex, when one controls for which group the respondent belongs to. These results must be interpreted cautiously as our samples are relatively small. They, however, seem to indicate that other factors than age and sex are the main determinants for a person’s attitude towards research.
In grading importance of physician’s motives to conduct medical research altruistic motives were highly rated by a large proportion in all groups, with cancer trial nonparticipants rating these motives the highest. This could seem inconsistent with the large proportion of respondents that regarded the motive of promoting doctors’ own careers as either important or very important. This apparently self-contradictory high importance gradings of both altruism and ‘self-interest’ as motives for doctors merely reflect the area’s complexity. In the light of large-scale public health system retrenchment programmes in Denmark in recent decades it is interesting, that the wish to minimize total expenses via research was regarded to have only minor or no importance by approximately two-thirds in all groups. The finding that the group of respondents with ages between 35 and 50 years rated the motive of getting access to a new drug or new diagnostic tool less important than both younger and older respondents is difficult to interpret, but the difference is small.
It is not surprising, that the chronically diseased IBD-participants with a regular contact to research active university departments had a higher proportion of former trial participants than the cancer patients. It is however, surprising, that the majority of previous trial participants amongst both groups of cancer patients had had their attitudes changed in a negative direction, whilst the majority of IBD-participants had changed their attitudes in a positive direction. The difference is statistically significant but must be interpreted cautiously as the number of respondents amongst cancer trial participants and cancer trial nonparticipants is small. That IBD-participants, whose former trial participation in a majority had been related to their bowel disease, had had their attitudes changed positively is maybe explained by our department having a long tradition for a special concern for ethical problems in research and patient care. This probably have had an impact on the experiences of the patients attending the department.
It is an important finding, that large majorities of respondents a priori had a positive attitude towards clinical trials in general. This is in agreement with previous findings [25–28]. It was expected that respondents in the group of cancer trial nonparticipants would have a less positive a priori attitude. It is, however, surprising that even these respondents stated such high degrees of positive attitudes towards clinical trials.
As expected answers revealed a significantly more positive attitude towards both personal participation and participation of others amongst both groups of trial participants, as compared with cancer trial nonparticipating respondents. At the same time considering trial participation as a moral obligation was rejected by the majority amongst both cancer trial participants, cancer trial nonparticipants, IBD-participants, outpatients, and the public . As argued by Rossel this way of thinking implies ethical problems, as a person willing to accept a certain good (i.e. the new treatment) procured by a social activity (clinical trial), but who is not willing to contribute to the social activity being a prerequisite for the availability of the good can be characterized as a ‘free rider’ . The results are probably another expression of an apparent conflict between rights and duties in modern societies with an increasing tendency to focus on individual benefits.
A majority amongst both cancer trial participants and IBD-participants stated that the presence of public research ethics committees had an impact on their decisions. That a clinical study has been reviewed and approved by an ethics committee apparently gives a sense of security and probably increases willingness to participate, which emphasizes the importance of such information. It must, however, be noted that at least some respondents probably were not a priori aware of the existence of this official control system .
In contrast to trial participants, a majority of cancer trial nonparticipants had a negative or a hesitating opinion of the principle of randomization, and several expressed a resentment towards this principle in free text responses. The importance of these aspects has also been found by others [4, 20, 31–34]. It is significant, that a major reason for a critical attitude towards ‘the drawing of lots’ was the fact, that the disease was a potential life-threatening condition. However, as found in the study by Fallowfield et al. further information can increase willingness to participate in trials, although a certain proportion of patients probably do not wish to participate, whatever information is provided .
Trial participants amongst both cancer patients and patients with inflammatory bowel disease gave almost identical answers concerning a priori attitudes towards clinical trials, the necessity of testing, attitudes towards both participation of self and others, importance of research ethics committees, and finally the issue of a possible moral obligation to participate. These similarities in answering indicates that the attitudes – at least concerning these issues – are to a large extent independent of age, gender, disease and potential burdens that are part of the trials.
In contrast to the overall positive attitudes found amongst actual trial participants, the attitudes amongst cancer trial nonparticipating respondents towards the same issues in general were considerably more critical, although a surprisingly high proportion stated positive a priori attitudes towards trials, and almost all recognized the necessity of testing. It is furthermore interesting that only some cancer trial nonparticipants were frankly negative towards potential self-participation and/or participation of others.
In grading the importance of different motives for participation both self-centred and altruistic motives were highly rated by a large proportion in both groups of trial participants. These findings are in accordance with findings in other studies [13, 24, 25, 27, 28, 32, 35–37]. It is significant, that a majority in both groups of trial participants rated the possibility of closer monitoring either important or very important. In addition the majority of IBD-participants expressed a high grade of satisfaction by participating in the trials, primarily because of the feeling of being ‘specially handpicked patients’ . The importance of this phenomenon was also shown in a questionnaire study by Slevin and coworkers, who examined the aspects of research trials which were considered appealing or unappealing by patients. The most appealing aspects were expectations of being more closely monitored, receiving more extensive information and being treated by a doctor with a special interest in their disease .
High satisfaction scores were recorded by trial participants concerning the initial oral and written information, although a rather large minority of cancer trial participants were not fully satisfied. In contrast, the information was only rated fully satisfactory by little more than half of cancer trial nonparticipating respondents. An important prerequisite for patients giving meaningful consent to participate is sufficient information. This is probably particularly important in patients with serious diseases, where consequences of choices can seem decisive. In fact, some cancer trial nonparticipants stated that the primary reason for not giving consent was the lack of sufficient information.
Although the data concerning experiences during the trials must be interpreted with caution – due to the failure of answering from more than half the respondents – it is reassuring, that a majority of respondents were relatively content with the total information given, and that the general impression of participating in the trial was either very positive or positive in a majority.
In the group of IBD-participants the most important factor in achieving high satisfaction scores and willingness of almost all respondents to participate in a future trial and to advise family or friends to do the same was the fact that these patients only saw one physician at control visits . In contrast, the most frequent theme related to negative experiences amongst cancer trial participants was a strong discontent about seeing too many physicians at check-up appointments who were not always perceived competent. This experience of a shifting panorama of passing doctors in the out-patient clinic on days of check-up appointments, leaves an impression amongst patients of being ‘just a number in a row’. Although more than half of the respondents did not answer the second and third questionnaires, the statements from the remaining respondents were almost uniform.
Because a large majority of the remaining respondents in fact stated their concerns about this, it is a message of paramount importance not only in research but also with a perspective for all clinical work, that patients have a right to be taken seriously as human fellow-beings. The importance of a confident partnership between patient and physician/researcher should not be underestimated. The possibility of recruiting larger proportions of eligible patients in the future than today is maybe realistic, if researchers remember and acknowledge this, as high levels of positive attitudes towards many different aspects of clinical research are found in the public, amongst out-patients , amongst participants in noncancer trials , amongst participants in cancer trials, and even amongst patients renouncing participation in cancer trials.