Ethical aspects of clinical trials: the attitudes of participants in two non-cancer trials

Authors


: Dr S. M. Madsen, Department of Medical Gastroenterology C, Copenhagen University Hospital at Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark (fax: +45 44 94 40 56; e-mail: smadsen@dadlnet.dk).

Abstract

Abstract. Madsen SM, Holm S, Davidsen B, Munkholm P, Schlichting P, Riis P (Copenhagen University Hospital in Herlev, Slagelse County Hospital, Slagelse, Hvidovre Hospital, University of Copenhagen, Denmark and University of Manchester, UK). Ethical aspects of clinical trials: the attitudes of participants in two non-cancer trials. J Intern Med 2000; 248: 463–474.

Objectives. To investigate attitudes to clinical trials in non-cancer trial participants.

Design. Questionnaires at entry, during, and after participation in a clinical study.

Setting. Participants in: (i) ROC: a clinical study comparing systemic interferon-α-2A treatment vs. prednisolone enemas in ulcerative colitis; and (ii) MRCRUC: a clinical study investigating low-field magnetic resonance imaging as a new modality for the evaluation of patients with inflammatory bowel disease.

Subjects. Thirty-two patients in ROC and 47 patients in MRCRUC.

Outcome measures. Attitudes towards different aspects of clinical research.

Results. The majority found scientific testing of clinical methods necessary, having positive attitudes towards both participation by themselves and others. The creation of a personal moral problem by denying participation was rejected by a large majority, and still both personal and altruistic motives for participation were highly rated. An important motive for accepting inclusion was the expectation of being ‘a special patient’ during the trial. The presence of research ethics committees controlling clinical research had a significant positive impact on decisions to participate, and drawing lots and blinding were found problematic by only a minority. Patients valued their satisfaction with participation in the trials highly, and would almost all accept a request to participate in future trials. The most important reason for this was a feeling of receiving better care and information than expected outside a trial setting, primarily determined by the patients seeing only one physician during the trials. A pronounced wish to obtain follow-up information was expressed.

Conclusion. Attitudes towards medical research are positive with both altruistic and nonaltruistic motives for participation. Expectations of being treated as ‘a special patient’ in the trial were important in accepting to participate. Seeing the same physician at control visits was an important factor for satisfaction with participation.

Introduction

A decreasing fraction of eligible patients have been recruited to clinical trials world-wide in recent years. This has been most pronounced and debated in serious diseases [1–9]. The decline in willingness to participate in clinical trials can only partly be explained by physician factors [2, 10–13], and patient factors have gained increasing importance in recent years [12–14].

There is a lack of knowledge about attitudes towards clinical research, how patients actually experience trial participation, and why patients accept or refuse to participate. To investigate attitudes amongst non-cancer research participants towards clinical research, and experiences during actual participation, we performed a questionnaire-survey amongst patients included in two clinical trials. We further wanted to compare these results with the results from a survey amongst potential trial participants in out-patient clinics and in the background population [15].

Materials and methods

Questionnaires were handed out to participants in two clinical studies (ROC and MRCRUC) performed on an out-patient basis at Copenhagen University Hospital in Herlev during 1995–98.

ROC 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.) for 12 weeks or prednisolone enemas (Predniment, Ferring Inc.) for 30 days. A total of 32 patients (19 men, 13 women) were randomized. The study was time-consuming for the patients, including several invasive and unpleasant procedures (colonoscopies) [16]. Questionnaires were given at study entry, after treatment termination, and after a follow-up period. Patients, who were secondarily excluded before full treatment had been given, only completed two questionnaires.

MRCRUC was a consecutive diagnostic study evaluating low-field magnetic resonance imaging in active inflammatory bowel disease. A total of 47 patients (25 men, 22 women) participated in the study, imposing only noninvasive procedures (three magnetic resonance imaging procedures, and a leucocyte scintigraphy), limited time consumption, and little discomfort (to be reported in a later publication). Questionnaires were given at study entry, after the second magnetic resonance imaging, and at study termination. Patients, who underwent ‘curative’ surgery after the second magnetic resonance imaging, only completed two questionnaires.

The questionnaires dealt with attitudes towards different aspects of clinical trials, including satisfaction with participation. Most questions were in a multiple-choice form, with an opportunity to add free text to some of the questions.

Comparisons between answers from ROC, MRCRUC, out-patient clinics, and public background population were only made when the questions asked were phrased identically.

Statistical analyses were performed using GraphPad Prism version 3.00 for Windows (GraphPad Software, San Diego, CA), using nonparametric statistical tests (Mann–Whitney tests and Wilcoxon–Pratt signed rank tests) with 0.05 as the level of significance. All P-values are given as two-tailed.

All approached patients in both clinical studies gave both verbal and written informed consent before answering questionnaires. The survey fulfilled the demands of Danish law and the Helsinki Declaration II including later amendments, and was approved by the Research Ethics Committee of Copenhagen County (reg. no. KA 95059).

Results

All patients answered the questionnaire at study entry. All patients in ROC (100%) and 44 (94%) of the patients in MRCRUC answered the ‘during study’ questionnaire. Twenty-one patients in ROC (66%) and 34 (72%) patients in MRCRUC answered the ‘after study termination’ questionnaire. Three MRCRUC patients did not answer the ‘during study’ questionnaire due to secondary exclusions. The missing ‘after study termination’ questionnaires are explained by secondary exclusions in ROC and by termination of study participation after the second magnetic resonance image in MRCRUC. All patients answered all questionnaires given. A few questions were not answered by all patients.

The median age (25% and 75% percentiles in parenthesis) was 40 years in ROC [28–55], and 29 years in MRCRUC [25–42]. Thus ROC respondents were older than respondents in MRCUC (P = 0.03). Approximately half of the patients had previously taken part in clinical trials (Table 1), most of which had been related to their bowel disease.

Table 1.  Fraction of former trial participants amongst respondents and pattern of change in opinion
  Gradings/choices (percentages in brackets)
Question ROCMRCRUCROCMROPCPUB
  1. ROC: clinical study comparing two treatment regimens in ulcerative colitis; MRCRUC: clinical study investigating a new diagnostic modality; ROCMR: ROC + MRCRUC; PUB: background population; OPC: out-patient clinics.

Have you previously taken
 part in a clinical trial?
Yes
No
14 (43.8)
18 (56.3)
24 (51.1)
23 (48.9)
38 (48.1)
41 (51.9)
49 (38.3)
78 (60.9)
 54 (16.6)
268 (82.5)
Blank answers 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.8)  3 (0.9)
Did your participation in clinical
 trials change your attitude
 towards such trials?
Yes, I had a positive change in attitude
Yes, I had a negative change in attitude
No, I had no change in attitude
 9 (64.4)
 5 (35.7)
 0 (0.0)
22 (91.7)
 2 (8.3)
 0 (0.0)
31 (81.6)
 7 (18.4)
 0 (0.0)
 7 (14.3)
 1 (2.0)
40 (81.6)
 14 (25.9)
  5 (9.3)
 36 (64.8)
Blank answers 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.0)  0 (0.0)

Former trial participation – impact on attitudes towards clinical trials

Former trial participation had changed the attitude towards trials in a positive direction in 80% of respondents in the two trials (ROC + MRCRUC = ROCMR). When comparing these results with those from the survey in the public background population and out-patient clinics [15] we found a higher degree of positive changes in opinion amongst ROCMR respondents (ROCMR vs. public background population: P = 0.0003; ROCMR vs. out-patient clinics: P < 0.0001; public background population vs. out-patient clinics: P = 0.7; ROC vs. MRCRUC: P = 0.2; Table 1).

As in the survey in out-patient clinics and public background population [15], a recurrent reason for a negative change given in free text responses was the lack of feedback about results of trials they had participated in. Several respondents motivated their positive change in attitudes by having felt as ‘hand-picked’ patients, receiving better care and information than they would have expected outside a trial.

Attitudes towards clinical trials at study entry

Respondents from ROCMR had a more positive attitude than those from out-patient clinics, which again were more positive than public background population respondents (ROCMR vs. public background population: P < 0,0001; ROCMR vs. out-patient clinics: P = 0.052; public background population vs. out-patient clinics: P = 0.04; Table 2). In free text the large majority expressed altruistic reasons for their positive attitude. A few trial participants stated, that their reservations primarily stemmed from ‘trial scandals’ in the media, and some were concerned about the possible commercially driven motives for trials and/or doctors seeking personal benefits.

Table 2.  Attitudes towards medical research
  Gradings/choices (percentages in brackets)
Question ROCMRCRUCROCMROPCPUB
  1. ROC: clinical study comparing two treatment regimens in ulcerative colitis; MRCRUC: clinical study investigating a new diagnostic modality; ROCMR: ROC + MRCRUC; PUB: background population; OPC: out-patient clinics.

How is your general attitudeVery positive5 (15.6)8 (17.0)13 (16.5)11 (8.6)20 (6.2)
 towards clinical trials?Positive17 (53.1)25 (53.2)42 (53.2)59 (46.1)109 (33.5)
 Positive with reservations10 (31.3)13 (27.7)23 (29.1)47 (36.7)161 (49.5)
 Generally negative, realize necessity0 (0.0)1 (2.1)1 (1.3)4 (3.1)23 (7.1)
 Negative0 (0.0)0 (0.0)0 (0.0)1 (0.8)3 (0.9)
 No opinion0 (0.0)0 (0.0)0 (0.0)6 (4.7)8 (2.5)
 Blank answers0 (0.0)0 (0.0)0 (0.0)0 (0.0)1 (0.3)
 
Do you think it necessary toAlways21 (65.6)30 (63.8)51 (64.6)80 (62.5)192 (59.1)
 examine ‘new’ drugs/In most instances9 (28.1)16 (34.0)25 (31.6)36 (28.1)116 (35.7)
 investigations using scientificNot in all instances, but in some1 (3.1)1 (2.1)2 (2.5)11 (8.6)13 (4.0)
 methods before they areIn no instances1 (1.3)0 (0.0)1 (1.3)0 (0.0)1 (0.3)
 implemented in clinical practice?Blank answers0 (0.0)0 (0.0)0 (0.0)1 (0.8)3 (0.9)
 
How is your general attitudePositive24 (75.0)35 (74.5)59 (74.7)67 (52.3)118 (36.3)
 towards your own potentialHesitating8 (25.0)12 (25.5)20 (25.3)49 (38.3)167 (51.4)
 participation in a clinical trial?Negative0 (0.0)0 (0.0)0 (0.0)11 (8.6)39 (12.0)
 Blank answers0 (0.0)0 (0.0)0 (0.0)1 (0.8)1 (0.3)
 
How is your general attitudePositive24 (75.0)36 (76.6)60 (75.9)67 (52.3)143 (44.0)
 towards a person in your familyHesitating7 (21.9)10 (21.3)17 (21.5)51 (39.8)152 (46.8)
 or amongst your close friendsNegative1 (3.1)1 (2.1)2 (2.5)7 (5.5)25 (7.7)
 participating in a clinical trial?Blank answers0 (0.0)0 (0.0)0 (0.0)3 (2.3)5 (1.5)

Almost all respondents considered it necessary to test new drugs or diagnostics scientifically before implementation in clinical practice. There were no statistically significant differences between groups (Table 2). A majority of respondents stated that their primary reason for finding research necessary, was the concern of possible unknown and unwanted effects of implementing something new without testing.

Approximately 75% of respondents had a positive attitude towards personal participation in a clinical trial, whilst the rest were hesitant. ROCMR respondents had a more positive attitude towards personal participation than patients in out-patient clinics, which again were more positive than public background population respondents (ROCMR vs. public background population: P < 0.0001; ROCMR vs. out-patient clinics: P = 0.003; public background population vs. out-patient clinics: P = 0.006; Table 2). Several patients stated hopes for a personal benefit, a wish to help future patients, and a wish to make a personal contribution in the struggle against the disease, as the primary reasons for their positive attitude. As a typical example one respondent wrote:

I feel an obligation to participate, as it will bring benefits to both myself and future patients in the same situation as mine. In addition you should contribute to your own recovery.

The majority of respondents in ROCMR were positive towards family or friends participating in trials. They had a higher degree of positive attitude than found in out-patient clinics and public background population (ROCMR vs. public background population: P < 0.0001; ROCMR vs. out-patient clinics: P = 0.006; public background population vs. out-patient clinics: P = 0.1; Table 2). The same altruistic reasons as those regarding self-participation were given in free text responses.

Presence of research ethics committees – impact on decisions to participate

The majority of respondents stated that the existence of legally based public research ethics committees in Denmark had an impact on their decision to participate (ROC 71.0%; MRCRUC 53.2%; ROCMR 60.3%). Less than a third stated either that this had had no impact on their decision (ROC 22.6%, MRCRUC 31.9%, ROCMR 28.2%) or that they had no opinion on this issue (ROC 6.5%, MRCRUC 14.9%, ROCMR 11.5%). No difference between groups was found.

Declining to participate in the trial – a moral problem?

Only a minority of respondents felt that declining participation in the trial would have had created a moral problem (ROC 10.3%, MRCRUC 19.1%, ROCMR 15.8%), whereas the majority did not feel this (ROC 75.9%, MRCRUC 61.7%, ROCMR 67.1%), or had no opinion on the issue (ROC 13.8%, MRCRUC 19.1%, ROCMR 17.1%). No difference between groups was detected.

Trial technicalities – impact on attitudes towards clinical trials

Approximately half the respondents had a positive opinion towards the principle of randomization, with a trend towards ROC respondents being more positive (P = 0.06). There were no differences between ROCMR, public background population and out-patient clinics (Table 3). Almost all respondents stated in free text, that the primary reason for their attitude was that drawing lots was the most just and fair method to ensure a random distribution between groups.

Table 3.  Attitudes towards the use of drawing lots (i.e. randomization) and blinding of treatments in a clinical trial
  Gradings/choices (percentages in brackets)
Question ROCMRCRUCROCMROPCPUB
  1. ROC: clinical study comparing two treatment regimens in ulcerative colitis; MRCRUC: clinical study investigating a new diagnostic modality; ROCMR: ROC + MRCRUC; PUB: background population; OPC: out-patient clinics.

How are your opinion towardsPositive23 (71.9)21 (44.7)44 (55.7)60 (46.9)181 (55.7)
 drawing lots (i.e. randomization)Hesitating6 (18.8)22 (46.8)28 (35.4)44 (34.4)80 (24.6)
 between treatments in clinical trials?Negative3 (9.4)4 (8.5)7 (8.9)21 (16.4)61 (18.8)
 Blank answers0 (0.0)0 (0.0)0 (0.0)3 (2.3)3 (0.9)
 
How does the need for blindingPositive influence9 (28.1)21 (44.7)30 (38.0)60 (46.9)172 (52.9)
 treatments influence your attitudeNo influence12 (37.5)14 (29.8)26 (32.9)35 (27.3)83 (25.5)
 towards clinical trials?Negative influence11 (34.4)12 (25.5)23 (29.1)21 (16.4)60 (18.5)
 Blank answers0 (0.0)0 (0.0)0 (0.0)12 (9.4)10 (3.1)

The influence on attitudes of the need for blinding treatments showed no significant differences between ROC and MRCRUC, with little less than a third being negatively influenced. Public background population respondents were more positive towards blinding techniques than ROCMR respondents (ROCMR vs. public background population: P = 0.01; Table 3). Several emphasized a pronounced desire to ‘know what was done to them’.

Reasons to participate

The respondents were asked to grade the importance for their choice to be included in the trial on a four-point scale (from very important to unimportant; Table 4).

Table 4.  Different reasons for consent to participation in a clinical trial
Question: How important was the following reasons
for your decision to participate in the trial?
Gradings/choices (percentages in brackets)
ROCMRCRUCROCMR
  1. ROC: clinical study comparing two treatment regimens in ulcerative colitis; MRCRUC: clinical study investigating a new diagnostic modality; ROCMR: ROC + MRCRUC.

‘The wish to get the “new”Very important13 (40.6)18 (38.3)31 (39.2)
 drug/investigation’Important15 (46.9)21 (44.7)36 (45.6)
 Minor importance3 (9.4)7 (14.9)10 (12.7)
 Unimportant0 (0.0)1 (2.1)1 (1.3)
 Blank answers1 (3.1)0 (0.0)1 (1.3)
 
‘The wish to be more closelyVery important21 (65.6)24 (51.1)45 (57.0)
 monitored regarding my disease’Important6 (18.8)19 (40.4)25 (31.7)
 Minor importance4 (12.5)3 (6.4)7 (8.9)
 Unimportant0 (0.0)1 (2.1)1 (1.3)
 Blank answers1 (3.1)0 (0.0)1 (1.3)
 
‘The wish to get a generally goodVery important3 (9.4)6 (12.8)9 (11.4)
 relation to the treating department’Important8 (25.0)6 (12.8)14 (17.7)
 Minor importance12 (37.5)14 (29.8)26 (32.9)
 Unimportant8 (25.0)21 (44.7)29 (36.7)
 Blank answers1 (3.1)0 (0.0)1 (1.3)
 
‘The wish to help future patients byVery important10 (31.3)22 (46.8)32 (40.5)
 helping to test “new” drugs/investigations’Important14 (43.8)20 (42.6)34 (43.0)
 Minor importance5 (15.6)4 (8.5)9 (11.4)
 Unimportant2 (6.3)1 (2.1)3 (3.8)
 Blank answers1 (3.1)0 (0.0)1 (1.3)
 
‘Positive experiences from formerVery important0 (0.0)3 (12.5)3 (7.9)
 participation in trials’Important3 (21.4)6 (25.0)9 (23.7)
 Minor importance4 (28.6)10 (41.7)14 (36.8)
 Unimportant6 (42.9)4 (16.7)10 (26.3)
 Blank answers1 (7.1)1 (4.2)2 (5.3)

Large majorities of respondents felt a ‘wish to get access to the new drug or new diagnostic tool’, a ‘wish to be more closely monitored’, and a ‘wish to help future patients’ as either very important or important, whereas both the ‘wish to obtain a good relation to the department performing the study’, and the ‘importance of positive experiences from former participation in trials’ was of either minor or no importance for the majority of respondents. No significant differences between groups were detected (Table 4).

In the survey in out-patient clinics and the public background population [15], we asked the respondents to grade the importance of the same reasons to participate on the same four-point scale, imagining a hypothetical situation where they had accepted participation in a clinical trial. The same distribution of answers was found as amongst ROCMR patients, relating to actual trial participation.

We further asked respondents to mention possible other factors influencing their decision to participate. Approximately a quarter of respondents stated a wish to become better as the primary reason, or that they had ‘a hope to get better care than if not participating’. A few also mentioned ‘possible benefits to future patients’ as a reason to participate.

Evaluation of information given prior to inclusion in clinical trial

We asked the patients to evaluate the oral and written information given prior to study entry on a 5-point scale. Answers were uniform with a high degree of satisfaction with the oral and written information given. The results for the scale for oral information were as follows: (1) too detailed and extensive: ROC 3.1%, MRCRUC 2.1%; (2) satisfactory, answered all my questions: ROC 90.6%, MRCRUC 93.6%; (3) excellent, but questions of doubt remained: ROC 6.3%, MRCRUC 4.3% (4) imperfect and not good enough: ROC 0.0%, MRCRUC 0.0%; (5) totally inadequate: ROC 0.0%, MRCRUC 0.0%. The result for written information were (1) too detailed and extensive: ROC 3.1%, MRCRUC 2.2%; (2) satisfactory, answered all my questions: ROC 81.3%, MRCRUC 78.3%; (3) excellent, but questions of doubt remained: ROC 9.4%, MRCRUC 17.4%; (4) imperfect and not good enough: ROC 6.3%, MRCRUC 2.2%; (5) totally inadequate: ROC 0.0%, MRCRUC 0.0%.

Experiences in trial

In the second and third questionnaire, patients were asked to judge the information given in response to questions asked during the trial. With no differences between groups, a large majority was very satisfied with the information given, which was also seen in responses regarding whether patients had had any unasked questions during the trial (Table 5).

Table 5.  Patient evaluation of participation in trial
  ROCMRCRUCROCMR
QuestionGradings/choices
(percentages in brackets)
During
study
After study
termination
During
study
After study
termination
During
study
After study
termination
  1. ROC: clinical study comparing two treatment regimens in ulcerative colitis; MRCRUC: clinical study investigating a new diagnostic modality; ROCMR: ROC + MRCRUC.

How do you value the informationFully satisfactorily, answered all my questions29 (90.6)19 (59.4)36 (76.6)28 (59.6)65 (82.3)47 (59.5)
 given from the doctors to you inExcellent, but some questions of doubt remained3 (9.4)2 (6.3)8 (17.0)6 (12.8)11 (13.9)8 (10.1)
 response to your questions askedImperfect, but yet acceptable0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)
 during the trial?Inadequate0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)
 Totally inadequate0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)
 Blank answers0 (0.0)11 (34.4)3 (6.4)13 (27.7)3 (3.8)24 (30.4)
 
Did you during the trial have anyYes, many questions0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)
 questions, you would have likedYes, single questions4 (12.5)1 (3.1)11 (23.4)6 (12.8)15 (19.0)7 (8.9)
 to ask, but did not ask?No, no questions28 (87.5)20 (62.5)33 (70.2)28 (59.6)61 (77.2)48 (60.8)
 Blank answers0 (0.0)11 (34.4)3 (6.4)13 (27.7)3 (3.8)24 (30.4)
 
How do you value the amountToo time-consuming1 (3.1)0 (0.0)3 (6.4)3 (6.4)4 (5.1)3 (3.8)
 of time spent in the studyOK31 (96.9)21 (65.6)40 (85.1)31 (66.0)71 (89.9)52 (65.8)
 I could have used more time0 (0.0)0 (0.0)1 (2.1)0 (0.0)1 (1.3)0 (0.0)
 Blank answers0 (0.0)11 (34.4)3 (6.4)13 (27.7)3 (3.8)24 (30.4)
 
How was the amount of timeMuch larger than I expected0 (0.0)0 (0.0)0 (0.0)1 (2.1)0 (0.0)1 (1.3)
 used in the study compared to theLarger than I expected6 (18.8)2 (6.3)6 (12.8)8 (17.0)12 (15.2)10 (12.7)
 expectation you got from theAs I expected26 (81.3)17 (53.1)35 (74.5)24 (51.1)61 (77.2)41 (51.9)
 information before the study started?Less than I expected0 (0.0)2 (6.3)3 (6.4)1 (2.1)3 (3.8)3 (3.8)
 Much less than I expected0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)
 Blank answers0 (0.0)11 (34.4)3 (5.4)13 (27.7)3 (3.8)24 (30.4)
 
How is your general impressionVery positive8 (25.0)5 (15.6)11 (23.4)6 (12.8)19 (24.1)11 (13.9)
 of participating in the trial?Positive19 (59.4)13 (40.6)30 (63.8)22 (46.8)49 (62.0)35 (44.3)
 Both positive and negative4 (12.5)3 (9.4)2 (4.3)6 (12.8)6 (7.6)9 (11.4)
 Negative0 (0.0)0 (0.0)1 (2.1)0 (0.0)1 (1.3)0 (0.0)
 Very negative0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)
 Blank answers1 (3.1)11 (34.4)3 (6.4)13 (27.7)4 (5.1)24 (30.4)
 
Did your experiences during the trialYes, in a positive direction8 (25.0)3 (9.4)9 (19.1)10 (21.3)17 (21.5)13 (16.5)
 change your general attitude towardsYes, in a negative direction0 (0.00)0 (0.00)0 (0.00)0 (0.00)0 (0.00)0 (0.00)
 clinical trials?No change24 (75.0)18 (56.3)35 (74.5)24 (51.1)59 (74.7)42 (53.2)
 Blank answers0 (0.0)11 (34.4)3 (6.4)13 (27.7)3 (3.8)24 (30.4)

Only a few respondents stated, that the trial had been too time-consuming; the time needed for the trial was in agreement with the expectations in a large majority (Table 5).

The general impression of trial participation was by a large majority regarded either very positive or positive. There were no differences between groups (Table 5).

We further asked the respondents to describe both positive and negative experiences from the trials in free text. The most frequent theme concerning positive experiences, given by a majority of patients, was an extra confidence created by the feeling of being a ‘special, hand-picked’ patient. These participants believed that they had received better care, more extensive information, more extensive insight into their disease, and closer control, than they would have experienced outside a trial setting. An important determining factor was the importance of seeing the same physician at each control visit, in contrast to the routine course of outpatient based controls, where the patients had been used to seeing a number of different physicians. Other recurrent themes for a positive experience included the feeling of helping future patients, helping science in general, and a feeling of doing something active for themselves. Statements from two patients largely cover the typical substance in the free text responses:

I have had a positive experience participating in this trial. I believe the main reason for this is that I saw the same doctor at each visit. I was confident with him and felt that I received a lot more information than I supposedly would have if I had not participated in the trial. Normally, when I come to the out-patient clinic with a relapse in my disease, I usually see a new doctor almost each time.

It is a nice feeling to know that I have helped both myself and future patients by my participation in this trial. I'm glad that I have done something active to contribute.

Only a few respondents stated reasons for negative experiences, most of which underlined unpleasant experiences during trial-associated investigations (endoscopies, ingestion of contrast fluid, etc.), and too much time spent during the trial.

The patients were further asked whether their experiences had changed their general attitude towards clinical trials. The majority stated no change in attitude, whilst a quarter stated a change in attitude in a positive direction. None stated a change in a negative direction. No differences were seen between groups (Table 5). In free text responses about their positive changes in attitudes the most important factor was that they – for some, surprisingly – had not been treated as ‘just another number in the row’ but as an individual, important human being, given all the necessary information with no apparent time limits. Three respondents wrote:

The doctor always took good time to inform me, and he always answered my questions very thoroughly. This has been a surprise for me, albeit a positive one, as I at ‘normal’ control visits usually am not receiving this quality of information. I didn't feel like just another guinea-pig.

I didn't feel like just another experimental person, but as a human being with a disease taken seriously. You are not just a number in a row.

I've felt, that good time was taken – more than expected. I have felt confident about things, and have not just been trial participant B7.

The patients were asked whether they would participate in a clinical trial again. Only one ROC respondent did not want to participate again. Whether patients would advise family members or close friends to participate followed the same pattern of responses (Table 6).

Table 6.  Attitudes during and after actual study towards possible future participation in a clinical trial
  ROCMRCRUCROCMR
QuestionGradings/choices
(percentages in brackets)
During
study
After study
termination
During
study
After study
termination
During
study
After study
termination
  1. ROC: clinical study comparing two treatment regimens in ulcerative colitis; MRCRUC: clinical study investigating a new diagnostic modality; ROCMR: ROC + MRCRUC.

Would you, if you in the future wereYes17 (53.1)12 (37.5)21 (44.7)13 (27.7)38 (48.1)25 (31.7)
 asked, participate in a clinicalMaybe14 (43.8)9 (28.1)23 (48.9)21 (44.7)37 (46.8)30 (38.0)
 trial again?No1 (3.1)0 (0.0)0 (0.0)0 (0.0)1 (1.3)0 (0.0)
 Blank answers0 (0.0)11 (34.4)3 (6.4)13 (27.7)3 (3.8)24 (30.4)
 
If a person amongst your familyNo, under no circumstances1 (3.1)1 (3.1)2 (4.3)1 (2.1)3 (3.8)2 (2.5)
 or close friends was asked aboutProbably not, but yet maybe2 (6.3)1 (3.1)2 (4.3)4 (8.5)4 (5.1)5 (6.3)
 participating in a trial, and he/sheMaybe, but it would depend on many things13 (40.6)9 (28.1)21 (44.7)17 (36.2)34 (43.0)26 (32.9)
 asked you for advice, would youYes, probably16 (50.0)10 (31.1)19 (40.4)12 (25.5)35 (44.3)22 (27.9)
 advise him/her to participate?Blank answers0 (0.0)11 (34.4)3 (6.4)13 (27.7)3 (3.8)24 (30.4)

The majority of respondents gave free text answers stating reasons for willingness to participate and advise close kindred to do the same. Almost uniform reasons were wanting to help future patients, the respondents themselves, and/or science in general. Additionally, a few respondents stated a moral obligation to participate. It was emphasized, however, by most responses, that decisions by relatives or friends on whether or not to participate were highly personal, and that any decision, positive or negative, should be accepted and supported.

General comments about the trial in free text showed that several patients strongly wished to get a post-trial feedback about the results.

Discussion

Response rates in this survey were very high. The three secondarily excluded MRCRUC patients who answered the primary questionnaire were kept within the present study material, as they were full participants in the clinical study. The proportion of respondents answering the second and third questionnaire was high enough to consider the answers representative for the whole group.

It was not surprising that approximately half the respondents had formerly participated in trials, considering their relation to a research-active university department with a primary interest in inflammatory bowel disease. A rather large majority had changed their attitudes towards clinical trials in a positive direction as a result of this former experience. The reason given was the feeling of receiving better care and information than outside a trial-setting. This finding contrasts with repeated media statements in recent years, implicating trial participation as a traumatic experience for many patients [17].

As in the out-patient clinics and public background population studies [15], a common reason for a negative change in attitude after former trial participation was the lack of follow-up information regarding results. It is understandable that patients with such experiences are disappointed. Such information should be an obligatory and a natural part of a research project.

It is significant that a large majority of respondents a priori had a positive attitude towards clinical trials, based on primarily altruistic motives. This result is in agreement with findings of others [18, 19], and was also found in our survey in the public background population and out-patient clinics studies [15]. It is, however, interesting that the respondents in the present survey – who in contrast to those in public background population and out-patient clinics had faced an actual choice of whether to participate or not – had a more positive attitude than patients in out-patient clinics. This was again more positive than the healthy public background population respondents. These findings show that the closer a person comes to an actual trial, the more a positive attitude to trials is reported.

The a priori positive attitudes towards clinical trials were strengthened by almost all respondents finding scientific testing necessary before general implementation. The positive attitudes probably reflect the same phenomenon of ‘closeness’ to actual trials, with a closer relationship to the treating physicians/researchers, and a personal need for access to better treatments/diagnostics.

A majority stated that the presence of public research ethics committees had an impact on their decision to participate. Prior to their consent, all participants were informed both orally and in writing about the presence and structure of the ethics committee (including the majority of lay persons), and that the trial in question had been reviewed and approved. At least for some participants this was probably new information, as a telephone survey in the general public in 1995 showed that only 30% of respondents were aware of the existence of such an official control system in Denmark [20]. The result emphasizes the importance of such information.

The high percentages of acceptance of randomization amongst respondents are surprising considering that this issue has often been discussed as problematic for patients. In addition, others have found randomization procedures to affect attitudes negatively in a relatively high proportion of patients. A study by Llewellyn-Thomas et al., comparing trial entry decisions in a hypothetical cancer trial of 60 women with breast cancer vs. 60 women with benign breast disease, found the primary reason for refusing the hypothetical trial entry to be aversion to the process of randomization in both groups [21]. It is thought-provoking, remembering that only ROC was a randomized study, that ROC respondents had a tendency towards being more positive in attitude than MRCRUC respondents, who had not actually experienced the randomization procedure. With this context in mind, it is also significant that an almost uniform statement in free text responses was the acknowledgement of randomization as the most just and fair way to distribute patients between test interventions.

The results showing the public to be more positively influenced in attitudes by the need for blinding treatments than actual trial participants (ROCMR) is interesting. The healthy nonhospitalized respondents in the public background population – at some distance to an actual trial setting – related to this issue in a purely hypothetical manner, whereas ROCMR respondents possibly considered the issue more concretely. Therefore, although neither of the actual studies were blinded, both groups of respondents wanted to ‘know what was done to them’.

It must be emphasized, that patients included in a combined blinded and randomized study may see problems not relevant for the patients included in the two trials in the present study.

It is interesting that the two groups of patients (ROC and MRCRUC) gave almost identical answers to most questions, in spite of the considerable difference in discomfort during their respective trials. This indicates that the attitudes are independent of the burdens of the trials.

Trial participation being considered a moral obligation towards society and/or future patients was rejected by the majority. This is probably another expression of an apparent conflict between rights and duties in modern societies, with an increasing tendency towards bringing the ‘self’ in the centre.

In grading the importance of different motives for actual participation in the trials, both self-centred and altruistic motives were highly rated by a large majority of respondents. These findings are in accordance with findings in other studies [12, 18, 22–27]. The findings of Cassileth and coworkers, that patients stated altruistic reasons for others to participate in trials, whilst they, when regarding self-participation, stated self-centred motives [24], were not seen in the present study.

The importance of the phenomenon of being ‘specially handpicked patients’ was also shown in a questionnaire study by Slevin and coworkers, who examined which aspects of research trials were considered appealing or unappealing for 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 [28]. The impact on satisfaction of an experience of receiving extra benefits by participating in a trial has also been dealt with by Verheggen et al., who showed that if patients expected to be treated as a special kind of patients during the trial, they proved to be highly satisfied with the personal benefit experienced [29].

It is not surprising that the most important factor in achieving the high satisfaction scores in the present study was the single physician design of the trials. It is, however, a very important message, because settings in many trials are often based upon a shifting panorama of passing doctors in the out-patient clinic on days of control visits, leaving an impression amongst trial participants of being ‘just a number in a row’. We regard the single physician design as being the most significant factor in having achieved the result that almost all respondents were willing to participate in a future trial and to advise family or friends to do the same. Further, this result has an additional, important perspective for all clinical work, whether in a research setting or not.

An important result of the present study is the differences expected and actually felt by patients between being ‘in a trial’ and being ‘outside a trial’. These differences are expressed by several patients and are grounded in the general experiences that the patients have had in being chronically diseased with a need to be seen regularly both on an out-patient basis and during hospitalization periods. Several patients had hopes about being treated as ‘special, handpicked patients’ if they participated in the trial, and they were not disappointed. This, however, puts the general daily level of patient care and information outside trials – at least in our centre – in perspective. It cannot be satisfactory for the patients or the health system, if the only way that patients can get a satisfactory treatment – not only relating to ‘the golden standard’ in the technical sense – is by reaching out for a clinical trial, where resources are often larger. The result shows the need for creating equity in patient care, both inside and outside the trial setting, thereby avoiding a trial-nobility. This equity must, however, be secured by lifting the level of daily patient care and information, and not by tempering our demands inside trials.

Our results show a surprisingly high level of positive attitudes towards many different aspects of clinical research amongst patients attending our department. However, this department has a long tradition for a special concern about ethical problems in research and daily patient care, which has probably had an impact on the experiences and attitudes of the patients attending the department. Whether this level of positiveness is representative for Danish non-cancer patients participating in clinical research in general is unknown. However, our results are, at least, expressive of what can be achieved when major efforts are directed towards securing patient ethics.

Acknowledgements

The implementation of the studies was made possible by grants from (alphabetically): Aage Louis-Hansen's Foundation; Anna og Jakob Jakobsen's Foundation; Astra Denmark; Beckett-Foundation; Danish Hospital Foundation for Medical Research. Region of Copenhagen, the Faroe Islands and Greenland; Danish Medical Research Council; Danish Research Council for the Humanities; Hede Nielsen's Foundation; Ole Trock-Jansen and Spouse Foundations; Ove Villiam Buhl Olesen og Edith Buhl Olesen's Foundation; Roche A/S; Sigrid Rigmor Moran's Foundation, and Vibeke Binder & Povl Riis' Foundation.

Received 18 February 2000; revision received 24 May 2000; accepted 10 June 2000.

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