Informing breast cancer patients about clinical trials: a randomized clinical trial of an educational booklet

P. M. Ellis1,+, P. N. Butow2 and M. H. N. Tattersall3

1 Medical Oncologist Hamilton Regional Cancer Center, Hamilton, Ontario, Canada; 2 Medical Psychology Unit, 3 Department of Cancer Medicine, University of Sydney, Sydney, Australia

Received 7 January 2002; revised 4 April 2002; accepted 12 April 2002


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix 1. Hypothetical...
 References
 
Background:

To evaluate the impact of an educational booklet on women’s knowledge of and willingness to participate in a randomized clinical trial of treatment for breast cancer.

Materials and methods:

Women undergoing surgery for newly diagnosed early stage breast cancer were randomized to receive, or not, an information booklet explaining the need for and manner in which randomized trials are conducted.

Results:

Eighty-three women with newly diagnosed early stage breast cancer completed a questionnaire assessing attitudes to random clinical trials (RCTs) and were randomized to receive usual information treatment options provided from their oncologist, or the educational booklet in addition to usual information from their oncologist (42 usual information, 41 booklet). Fewer women who received the clinical trials booklet (40% versus 47%) would consider participating in the hypothetical clinical trial (P = 0.6). Mean knowledge scores increased for both groups; moreover, women who did not receive the booklet showed similar improvements to women who received the booklet [mean difference 0.09, 95% confidence interval (CI) –0.66 to 0.83]. In a multivariate analysis women who would consider participating in the clinical trial were more anxious [odds ratio (OR) 5.9, P = 0.02] had involved lymph nodes (OR 5.8, P = 0.02) and were less influenced by negative aspects of clinical trials (OR 7.7, P = 0.0001). After adjustment for these variables women who received the educational booklet were significantly less likely to consider trial participation (OR 0.22, P = 0.05).

Conclusions:

Educating women about clinical trials in this manner appears ineffective in improving recruitment to RCTs. Women appear to be more influenced by their perception of risk than understanding. This finding has ethical implications for communication of information about RCTs.

Key words: attitude to health, breast neoplasm, patient compliance, patient education, randomized controlled trials


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix 1. Hypothetical...
 References
 
Randomized clinical trials (RCTs) require the doctor to combine the traditional role of healer with that of trialist or researcher [1]. According to Pellegrino [2], society permits experimentation with human subjects because of the benefits that the whole society, as well as the experimental subject, may gain from the new medical knowledge. Therefore, a fundamental ethical issue surrounding participation in RCTs reflects a need to safeguard individual rights versus an obligation to society to facilitate research [3].

In order to safeguard individual autonomy, additional ethical requirements are imposed upon treatment received as part of a RCT [4]. There is an ethical obligation that trials be of sufficient quality to have a favorable impact on society in the future [5, 6]. Additionally, requirements for informed consent for clinical trials are often more stringent than those for treatment outside of the setting of a clinical trial [711]. The goal is to provide sufficient information about the treatments offered on the trial, the benefits, side effects and alternative treatment approaches, plus procedural information about the clinical trial for patients to make an autonomous decision.

Review of the literature suggests that the goals of informed consent for clinical trials are not always met [12]. A number of researchers have found that patients fail to recall much of the information presented to them during a consent interview [1316]. Patient information sheets for clinical trials are often too complex for many patients to read [17, 18]. Poor recall and understanding may also arise due to variation in the amount of information provided by doctors during the informed consent consultation. Williams and Zwitter [19] found considerable variation in the information that investigators state they would routinely give to patients considering entry into phase III clinical trials.

Several studies have examined ways to improve the provision of information about randomized trials. Davis et al. [20] randomized cancer patients to receive or not, the National Cancer Institute (NCI) booklet on clinical trials. Patients receiving the NCI booklet were more knowledgeable about clinical trials in general. Simes et al. [21] and Aaronson et al. [22] randomized patients considering entry into a specific clinical trial to receive more detailed information about the trial that was being discussed versus their standard practice. They found that patients who received more detailed information were more knowledgeable about the trial, but both authors observed a small (statistically insignificant) reduction in willingness to participate in the trial.

Earlier research by our group suggested that cancer patients and members of the general public have a poor understanding about the need for RCTs to establish the worth of new and existing treatments, or the manner in which this would happen [23, 24]. Many patients did not appear to understand the rationale for randomization. A number of women attending focus group interviews indicated that they would be more willing to consider participating in a clinical trial once they were better informed. The findings of a more recent larger survey suggested that women who were more knowledgeable about RCTs, in general, were more willing to consider participating in a trial themselves [25].

Many cancer patients are approached to participate in clinical trials soon after their diagnosis when they are feeling stressed and vulnerable [26]. Discussions about RCTs at this point may add to feelings of anxiety and uncertainty. In order to overcome this Baum [27, 28] has suggested that there is a need to educate the public about the need for RCTs and the manner in which they are conducted.

Patient education booklets are one type of intervention that has been evaluated in a number of different settings to improve information exchange. Educational booklets have been shown to increase knowledge in patients with arthritis and hypertension [29, 30]. Other authors report additional benefits including improved satisfaction [31], fewer GP visits, less referrals to physiotherapy and fewer hospital admissions among patients with back pain [32]; and reduced anxiety, greater physiologic recovery and improved mood among patients undergoing coronary artery bypass graft surgery [33]. This study reports the results of a RCT evaluating the impact of an informational booklet, explaining the need for and manner in which RCTs are conducted, on women’s knowledge of and willingness to participate in a RCT of treatment for breast cancer.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix 1. Hypothetical...
 References
 
The women in this study were identified from a larger study assessing knowledge and attitudes to RCTs, which has been reported elsewhere [25]. All women undergoing a definitive surgical operation (lumpectomy and axillary dissection or mastectomy) for early stage invasive breast cancer at the Sydney Breast Cancer Institute (SBCI) during 1998 were eligible for inclusion in this study. Women with locally advanced breast cancer treated initially with chemotherapy and/or radiotherapy were not eligible for this study. In addition, women were ineligible for this study if they had metastatic disease at presentation, were unable to read English or were unable to complete a questionnaire.

Women were identified via a multidisciplinary breast cancer meeting in which all new breast cancer cases from the preceding week were discussed. Women were approached after they had received news of their own histopathology results, but prior to seeing a medical oncologist to discuss further treatment options. The purpose of the research was explained and women were given an information sheet to read. Written informed consent for this study was obtained from women who agreed to participate. Institutional ethics committee approval was obtained from Central Sydney Area Health Service.

Women were asked to complete a baseline questionnaire (see below), then randomized centrally to a usual discussion about treatment options from their doctor (including clinical trials if appropriate), or an information booklet about clinical trials in addition to usual discussion about treatment options from their doctor. No attempt was made to try to standardize the usual information provided by the doctor. The information booklet explained the need for and manner in which RCTs are conducted. This was a short booklet which discussed what clinical trials are, how treatment is decided on a RCT, potential advantages and disadvantages of participating in a clinical trial and common misunderstandings about randomized trials identified from earlier research [23, 24]. It also provided a list of questions to help women find out more information from their medical oncologist about specific clinical trials appropriate to their own situation. The booklets were printed in black and white on neutral colored paper. Women receiving the booklet who wanted additional general information about clinical trials could also receive a more detailed booklet produced by the New South Wales Cancer Council. Four to six weeks later women were mailed a follow-up questionnaire to complete and return in a reply paid envelope. Information was collected from the women’s medical oncologist concerning disease data (tumor size, nodal involvement, histological grade, hormone receptor status), eligibility for inclusion into a randomized trial of adjuvant therapy, whether clinical trials were discussed with the patient, the outcome of such discussions and the actual treatment received.

Survey instruments
The baseline questionnaire measured:

demographic details including age, marital status, education, occupation, ethnicity and medical/allied health training;
Hospital Anxiety and Depression Scale (HADS) [34, 35];
women’s preferences for the amount of information they wish to receive from their doctor (three item scale previously described by Cassileth et al.) [36] and their level of involvement in clinical decision-making (five item scale previously described by Degner and Sloan) [37];
knowledge about the need for and manner in which RCTs are conducted using a seven item scale developed for this questionnaire;
attitudes to RCTs. This was a 36 item scale assessing the impact of individual items on women’s willingness to participate in randomized trials. This scale has high internal reliability (Cronbach {alpha} 0.96) [25] and measures four factors: perception of the positive aspects of clinical trials; perception of the negative aspects of clinical trials; perception of loss of control/inconvenience on a clinical trial and views about altruism. Higher scores (range 0–7) reflect greater willingness to participate in a RCT;
general willingness to participate in RCTs.

The follow-up questionnaire measured:

information and involvement in decision-making preferences;
knowledge about clinical trials;
attitudes to RCTs;
willingness to join a hypothetical trial of adjuvant therapy for breast cancer (see Appendix 1);
satisfaction with the amount of information in the consultation, communication skills of the doctor and the level of participation in the consultation. This scale has been extensively used by the Medical Psychology Unit to assess satisfaction in doctor–patient communication research [3840];
women’s use of the clinical trials booklet (four item scale—‘not at all’, ‘somewhat helpful’, ‘moderately helpful’, ‘very helpful’);
recollections of discussions about clinical trials (did your doctor discuss clinical trials with you?);
other sources of information.

Data analysis was undertaken using SPSS, version 6.1 (SPSS, Chicago, IL, USA) [41]. Analysis was by intention-to-treat. At the time of this study, few women were invited to participate in an actual clinical trial, therefore the main outcome of the randomized trial was willingness to join the clinical trial described in a hypothetical scenario. However, women were asked to make this decision at a salient time point (soon after making decisions about their own breast cancer treatment). Secondary outcomes included changes over time in women’s knowledge and attitudes towards randomized trials, plus women’s satisfaction. Descriptive information was collected on women’s reasons for agreeing, or not agreeing, to participate in the hypothetical trial. Differences in baseline variables between the randomized groups were assessed using {chi}2-tests or Student’s t-test. Differences in willingness to participate in the hypothetical breast cancer trial were assessed using {chi}2-test. Change scores for knowledge and attitudes to clinical trials were assessed using paired Student’s t-tests. A stepwise backward multivariate logistic regression was conducted to examine the impact of receiving the information booklet on willingness to participate in the hypothetical RCT after adjustment for the effects of confounding variables. Information on women’s use of the clinical trials booklet, other sources of information and their recollection of discussions about clinical trials will be presented in a separate paper.

Earlier research suggested that 15–20% of women with early stage breast cancer treated in the Medical Oncology Department at Royal Prince Alfred Hospital were recruited onto clinical trials [42]. A sample of 122 would be able to detect an increase from 20 to 45% with a power of 0.80 and a significance level of 0.05. An interim analysis was planned when approximately two thirds of women had been recruited. At this point 83 women had been recruited. A decision was made to close the trial at this time because of both a lack of efficacy and low salience of the intervention. Assuming a best case scenario (i.e. all the remaining women in the intervention group decided to join the trial) the difference between the groups would not have achieved statistical significance. The final study had a power of 0.60 to detect a difference of 25% and a power of 0.80 to detect a 35% difference in willingness to join the hypothetical trial.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix 1. Hypothetical...
 References
 
One hundred and one women underwent definitive surgical treatment for invasive breast cancer during the study period (Figure 1). Ninety-five women were approached about the study and 83 (87%) agreed to participate. Four women withdrew after randomization and follow-up questionnaires were returned by 67 (71%) of women. Demographic information on the 83 women randomized is shown in Table 1. Women randomized to receive the clinical trial booklet were on average 3 years older [95% confidence interval (CI) –1.5 to 7.5 years] than women in the control group, but this difference was not statistically significant. A greater proportion of women who received the booklet had received tertiary education, but again this difference was not significant (P = 0.44). Significantly more women who received the clinical trials booklet were classified as possible or definite cases of anxiety (63 versus 33%, P = 0.0008) and depression (21 versus 5%, P = 0.03) according to HADS. Disease characteristics of the 83 women are summarized in Table 2. The two groups were well matched according to tumor size, lymph node status, histological grade and hormone receptor status.



View larger version (26K):
[in this window]
[in a new window]
 
Figure 1. Flow diagram of the study population.

 

View this table:
[in this window]
[in a new window]
 
Table 1. Comparison of demographic characteristics of patients randomized to receive the clinical trials booklet or standard information
 

View this table:
[in this window]
[in a new window]
 
Table 2. Comparison of disease characteristics of women included in the evaluation of the clinical trials booklet
 
Over 95% of women wanted to receive all information whether good or bad from their doctor. These preferences remained stable over the 4–6 week study period. Short-term changes in women’s preferences for involvement in decision-making were evident. Twenty-two per cent of women would prefer to adopt a passive role in decision-making, 44% a collaborative role and 34% an active role. Preferences remained unchanged for 45 of 67 (68%) women in the follow-up questionnaire 4–6 weeks later. However, 11 (16%) women wanted a greater role in decision-making and 11 (16%) wanted the doctor to play a greater role in decision-making.

Knowledge scores were calculated by summing the number of correct responses to the seven items (range 0–7). The mean knowledge score was 4.1 (SD 2.0). Baseline knowledge was slightly higher among women randomized to receive the clinical trials booklet (difference 0.9, 95% CI –0.05 to 1.7, P = 0.06). There was a small increase in knowledge between baseline and reassessment 4–6 weeks later (mean 0.6 95% CI 0.2 to 0.9, P = 0.003). However, women who received the clinical trials booklet showed no greater improvement in knowledge than women in the control group (difference 0.09, 95% CI –0.66 to 0.83, P = 0.82).

Comparison was made of the four factor scores assessing attitudes to RCTs between women randomized to receive the clinical trials booklet and the control group. Higher scores equate to greater willingness to participate in randomized trials (range 0–7). There were no differences in baseline attitudes to randomized trials. Women’s attitudes to randomized trials changed over time. At follow-up, women were less influenced by positive aspects of clinical trials (–0.22, 95% CI –0.04 to –0.4, P = 0.02) and altruistic motivations (–0.23, 95% CI –0.04 to –0.43, P = 0.02). Their was no evidence of any change in women’s perceptions of the negative aspects of clinical trials (0.03, 95% CI –0.16 to 0.22, P = 0.73) or about practical issues/loss of control (0.06, 95% CI –0.17 to 0.28, P = 0.63).

In response to the initial questionnaire, 20 women (25%) would consider participating in clinical trials, 24 women (30%) would not and 35 women (45%) were unsure. In the follow-up questionnaire a scenario describing a hypothetical woman with a node-positive breast cancer was presented (see Appendix 1). Treatment options of tamoxifen or chemotherapy were described along with a hypothetical RCT in which women may receive tamoxifen alone, chemotherapy alone or chemotherapy followed by tamoxifen. Twenty-six women (43%) indicated they would be prepared to join the clinical trial, while 34 women (57%) were not prepared to. Data were missing for the remaining seven women. Fourteen women (47%) randomized to the standard information arm were prepared to join the clinical trial, compared with 12 women (40%) randomized to receive the clinical trials booklet. Therefore slightly fewer women (7%) receiving the clinical trials booklet than women in the standard information arm were willing to join the clinical trial, but this difference was not statistically significant (95% CI –32% to 18%, P = 0.60). There was no evidence of any difference between the groups in women’s satisfaction with the consultation (P = 0.65).

A multivariate logistic regression analysis was conducted to examine the impact of the clinical trials booklet on women’s decision to join the hypothetical clinical trial of adjuvant therapy for breast cancer, after adjustment for potential confounding factors. Demographic variables (age, education, medical/allied health training), disease variables (tumor size, nodal involvement) preferences for involvement in clinical decision-making, anxiety, depression, along with the four factor scores measuring attitudes to clinical trials were entered into the model. The results are summarized in Table 3. After adjustment for other variables, women who received the clinical trials booklet were significantly less likely to join the hypothetical clinical trial (OR 0.22, 95% CI 0.04–1.0, P = 0.05). Women with possible or definite cases of anxiety were more likely to join the clinical trial (OR 5.9, 95% CI 1.2–30.1, P = 0.02), as were women with involved lymph nodes (OR 5.8, 95% CI 1.1–28.8, P = 0.02). Women who were less likely to be influenced by negative aspects of clinical trials were also significantly more likely to join the hypothetical clinical trial (OR 7.7, 95% CI 2.3–25.2, P <0.0001).


View this table:
[in this window]
[in a new window]
 
Table 3. Results of the multivariate logistic regression analysis examining the impact of the clinical trial booklet on women’s decision to join a clinical trial after adjustment for potential confounders
 
Women were asked why they would choose to join or not to join the clinical trial. The responses are summarized in Table 4. The most common reasons given for choosing to join the clinical trial were that any of the treatments appear to be helpful (n = 10), there was nothing to lose by joining the clinical trial (n = 8) and altruistic motivations—helping to advance medical knowledge (n = 8) and helping other people (n = 8). Other reasons included the possibility of receiving better treatment (n = 6) and the stage of the disease (n = 5).


View this table:
[in this window]
[in a new window]
 
Table 4. Summary of women’s reasons for joining, or not joining, the clinical trial in the hypothetical scenario
 
There were a greater number of reasons why women would choose not to join the clinical trial. There were no major differences between the randomized groups. The reasons predominantly related to dislike about treatment allocation on a clinical trial and concerns about receiving one of the treatments offered on the clinical trial.


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix 1. Hypothetical...
 References
 
Earlier research by our group suggested that willingness to participate in randomized trials was associated with greater understanding of the issues involved [25]. These findings suggested that patient education about the need for and manner in which RCTs are conducted might improve patients’ understanding about randomized trials and lead to improved recruitment. However, the results of this study suggest that general education of patients about RCTs in this manner was an ineffective strategy in promoting recruitment to clinical trials.

Previous studies have demonstrated that patients receiving more detailed information about specific clinical trials have improved knowledge about those trials [21, 22]. However, women in this trial who received the clinical trial booklet showed no greater improvement in knowledge than women who received usual information about treatment options from their doctor. These findings suggest that factors other than knowledge or understanding about a trial may be more important in the decision to enter a clinical trial.

Characteristics associated with the women’s cancer were influential in the decision to join the clinical trial. We did not directly measure women’s estimate of their prognosis. However, nodal status is one of the major prognostic factors for breast cancer. Women with involved lymph nodes would be aware that this fact carries a greater risk of future relapse and death from breast cancer. These findings are supported by observations from Siminoff and others that women with early stage breast cancer who overestimate their prognosis with standard therapies are less likely to consider participating in a clinical trial [4345]. By chance, significantly more women randomized to the information booklet were classified as cases of anxiety and depression. Following adjustment for this imbalance, anxiety was still associated with increased willingness to join a clinical trial. Therefore women’s perception of the implications of their illness appears influential in their decision to join a randomized trial. The findings highlight the potential for subtle coercion when discussing both standard treatment options and clinical trials.

The results of this study suggest that women’s perceptions of the negative aspects of clinical trials (randomization, experimental aspects, greater uncertainty) are far more influential in decision-making than their perceptions about the advantages. Previous research has suggested that the main reasons patients give for joining a clinical trial are the potential to receive more effective treatments and helping future patients [46, 47]. In the follow-up questionnaire, women in this study appear less likely to be influenced by potential advantages of clinical trials. This finding may reflect a satisfaction bias with the treatment decision women made as only two women received adjuvant therapy as part of a clinical trial. However, an additional explanation is that women, having reflected on the issues over a few weeks, believed there were fewer advantages to participating in clinical trials than they originally considered.

There were a variety of reasons given by women for not agreeing to join the clinical trial of adjuvant therapy. The major reasons reflected specific concerns about the treatments offered on the trial (concern about side effects or wanting to avoid one of the treatments), or dislike about the allocation of treatment (want themselves or doctor to select treatment or dislike of random allocation). A desire by patients for a specific treatment recommendation from the doctor appears to be an important obstacle to recruitment to clinical trials [48], although a recent study by Fallowfield et al. [49] demonstrated that clearer explanations about randomization increased patients’ willingness to participate in trials in general.

Common reasons given by women for agreeing to join the clinical trial included ‘any of the treatments appear to be helpful’ and ‘there did not appear to be anything to lose by joining the trial’. These responses suggest an understanding of issues relating to equipoise. Equipoise exists when either individually or collectively, doctors are uncertain about the comparative merits of different treatment approaches. It is a crucial issue for doctors when deciding whether to participate in RCTs [3, 5, 50]. These findings support those of Fallowfield et al. [49, 51], that greater understanding of this issue by patients may also be an important factor in their decision to enter a randomized trial.

Unlike previous interventions [21, 22], we were unable to document any effect from the clinical trial booklet in this study in improving knowledge about clinical trials among women with breast cancer. Despite the lack of effectiveness on women’s knowledge, receiving the clinical trial booklet was associated with reduced willingness to participate in a clinical trial of adjuvant therapy for breast cancer. Patient education booklets have been shown to have a number of improved outcomes in a number of different settings [29, 32, 33, 52, 53]. In general, the information contained in these educational interventions was immediately relevant to the problem with which the patient presented. Few women in this trial were presented the option of participating in an actual clinical trial. The clinical trial booklet may have been ineffective because the information contained in it was not particularly salient to decision-making for the majority of women in this study. If so, the results highlight the importance of physician reinforcement of information about clinical trials.

There are some limitations to this study. The number of women included in the study was relatively small and approximately 25% of women did not complete the follow-up assessment. However, there were no major differences in baseline characteristics of those women not completing the follow-up assessment and those included in the analysis (data not shown). This study was conducted among women with early stage breast cancer. It is not clear whether these findings can be generalised to patients with other cancers considering entry into a clinical trial. Additionally, the motivation to participate in a clinical trial for patients with advanced or metastatic cancer may be quite different from those of patients with early stage disease.

Nevertheless, the findings of this study suggest that the decision to enter clinical trials in oncology is a complex interaction of patients’ pre-existing beliefs, the perception of the seriousness of their disease and endorsement of the trial by the physician. Strategies designed to educate patients about trials in general, or about specific clinical trials, have not proven effective in improving recruitment. Further research should examine more closely the exchange of information that takes place during the informed consent interview(s). In the interim it is important that patients’ concerns about the negative aspects of randomized trials be aired in consultation to ensure patient understanding and avoid undue coercion.


    Acknowledgements
 
Dr Peter Ellis was supported by a postgraduate scholarship from the National Health & Medical Research Council of Australia from 1997 to 1999.


    Appendix 1. Hypothetical clinical trial scenario
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix 1. Hypothetical...
 References
 
Now that you have made decisions about your own treatment we would like you to consider a hypothetical situation about a women called Sheila. Remember, while some of the details may appear similar to yours, the details refer to Sheila.

Sheila is a 56-year-old woman who has recently had a mastectomy for breast cancer. The cancer spread to several of her lymph glands. Radiotherapy was not recommended for Sheila. She has gone to talk to a medical oncologist who recommended that she have some additional treatment to reduce the chances of the cancer returning. In Sheila’s situation, both tamoxifen and chemotherapy, have been shown to be beneficial.

Tamoxifen is a hormonal tablet taken once per day for 5 years. The major side effects include hot flushes, vaginal dryness or itching, weight gain, mood changes and occasionally some nausea. Not all patients experience these side effects. Chemotherapy is given as a combination of injections and tablets over 6 months. The major side effects include nausea and vomiting, hair loss, sore mouth and eyes and diarrhea. There may also be an increased risk of infection. Not every patient experiences side effects and many of these side effects can be managed with medication.

Sheila’s doctor explained that either tamoxifen or chemotherapy would be beneficial to her. She (or Sheila’s doctor) could choose to have either one of these treatments. However, it is not known whether tamoxifen is better than chemotherapy, or whether combining tamoxifen and chemotherapy is better than either one on its own. Sheila’s doctor invites her to participate in an international clinical trial comparing these treatments. If she were to agree, she would either receive tamoxifen on its own, chemotherapy on its own, or tamoxifen plus chemotherapy. Her treatment would be chosen at random (neither Sheila nor her doctor would pick her treatment).

Sheila has the option of choosing either chemotherapy or tamoxifen, or joining the clinical trial comparing these treatments. Given the experience you have gained making decisions about breast cancer treatments, if you were Sheila, would you agree to participate in the clinical trial?


    Footnotes
 
+ Correspondence to: Dr P. M. Ellis, Hamilton Regional Cancer Center, 699 Concession St, Hamilton, Ontario, L8V 5C2, Canada. Tel: +1-905-387-9495; Fax: +1-905-575-6326; E-mail: peter.ellis{at}hrcc.on.ca Back


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Appendix 1. Hypothetical...
 References
 
1. Scoles L, Silagy C. Are clinical trials in general practice ethical? Aust Fam Physician 1993; 22: 182–183.[Medline]

2. Pellegrino ED. Beneficence, scientific autonomy, and self-interest: ethical dilemmas in clinical research. Camb Q Healthc Ethics 1992; 4: 361–369.

3. Lilford RJ, Jackson J. Equipoise and the ethics of randomization. J R Soc Med 1995; 88: 552–559.[ISI][Medline]

4. Beauchamp TL, Childress JF. Principles of biomedical ethics. New York: Oxford University Press 1994.

5. Lilford RJ. The substantive ethics of clinical trials. Clin Obstet Gynecol 1992; 35: 837–845.[ISI][Medline]

6. Palter SF. Ethics of clinical trials. Semin Reprod Endocrinol 1996; 14: 85–92.[ISI][Medline]

7. Miller C, Searight HR, Grable D et al. Comprehension and recall of the informational content of the informed consent document: an evaluation of 168 patients in a controlled clinical trial. J Clin Res Drug Dev 1994; 8: 237–248.

8. Rimer B, Jones WL, Keintz MK et al. Informed consent: a crucial step in cancer patient education. Health Educ Q 1984; 10 (Suppl): 30–42.

9. Dal Re R. Elements of informed consent in clinical research with drugs: a survey of Spanish clinical investigators. J Intern Med 1992; 231: 375–379.[ISI][Medline]

10. Tattersall MHN, Simes RJ. Issues in informed consent. In Williams CJ (ed.): Introducing New Treatments for Cancer: Practical, Ethical and Legal Problems. Chichester, UK: John Wiley & Sons 1992; 79–90.

11. Feldman-Stewart D, Chammas S, Hayter C et al. An empirical approach to informed consent in ovarian cancer. J Clin Epidemiol 1996; 49: 1259–1269.[ISI][Medline]

12. Cassileth BR, Zupkis RB, Sutton-Smith K et al. Informed consent: why are its goals imperfectly realized. N Engl J Med 1980; 302: 896–900.[Abstract]

13. Harth SC, Thong YH. Parental perceptions and attitudes about informed consent in clinical research involving children. Soc Sci Med 1995; 41: 1647–1651.[ISI][Medline]

14. Olver IN, Buchanan L, Laidlaw C et al. The adequacy of consent forms for informing patients entering oncological clinical trials. Ann Oncol 1995; 6: 867–870.[Abstract]

15. Sutherland HJ, Lockwood GA, Till JE. Are we getting informed consent from patients with cancer? J R Soc Med 1990; 83: 439–443.[Abstract]

16. Dunn SM, Butow PN, Tattersall MHN et al. General information tapes inhibit recall of the cancer consultation. J Clin Oncol 1993; 11: 2279–2286.[Abstract]

17. Grossman SA, Piantadosi S, Covahey C. Are informed consent forms that describe clinical oncology research protocols readable by most patients and their families? J Clin Oncol 1994; 12: 2211–2215.[Abstract]

18. Taylor KM, Bezjak A, Hunter R et al. Informed consent for clinical trials: Is simpler better? J Natl Cancer Inst 1998; 90: 644–645.[Free Full Text]

19. Williams CJ, Zwitter M. Informed consent in European multicentre randomised clinical trials—are patients really informed? Eur J Cancer 1994; 30A: 907–910.

20. Davis SW, Nealon EO, Stone JC. Evaluation of the National Cancer Institute’s clinical trials booklet. J Natl Cancer Inst Monogr 1993; 14: 139–145.[Medline]

21. Simes RJ, Tattersall MHN, Coates AS et al. Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment of cancer. Br Med J 1986; 293: 1065–1068.[ISI][Medline]

22. Aaronson NK, Visser-Pol E, Leenhouts GHMW et al. Telephone-based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials. J Clin Oncol 1996; 14: 984–996.[Abstract]

23. Ellis PM, Butow PN. Focus group interviews examining attitudes to randomised trials among breast cancer patients and the general community. Aust N Z J Public Health 1998; 22: 528–531.[ISI][Medline]

24. Ellis PM, Dowsett SM, Butow PN et al. Attitudes to randomised clinical trials among outpatients attending a medical oncology clinic. Health Expectations 1999; 2: 33–43.[Medline]

25. Ellis PM, Butow PN, Tattersall MHN et al. Randomised clinical trials in oncology: understanding and attitudes predict willingness to participate. J Clin Oncol 2001; 19: 3554–3561.[Abstract/Free Full Text]

26. Thornton H. Clinical trials: a brave new partnership? J Med Ethics 1994; 20: 19–22.[Abstract]

27. Baum M. New approach for recruitment into randomised controlled trials. Lancet 1993; 341: 812–813.[ISI]

28. Baum M. Clinical trials: a brave new partnership: a response to Mrs Thornton. J Med Ethics 1994; 20: 23–25.[ISI][Medline]

29. Maggs FM, Jubb RW, Kemm JR. Single-blind randomized controlled trial of an educational booklet for patients with chronic arthritis. Br J Rheumatol 1996; 35: 775–777.[ISI][Medline]

30. Watkins CJ, Papacosta AO, Chinn S et al. A randomized controlled trial of an information booklet for hypertensive patients in general practice. J R Coll Gen Pract 1987; 37: 548–550.[ISI][Medline]

31. O’Neill P, Humphries GM, Field EA. The use of an information leaflet for patients undergoing wisdom tooth removal. Br J Oral Maxillofac Surg 1996; 34: 331–334.[ISI][Medline]

32. Roland M, Dixon M. Randomized controlled trial of an educational booklet for patients presenting with back pain in general practice. J R Coll Gen Pract 1989; 39: 244–246.[ISI][Medline]

33. Cupples SA. Effects of timing and reinforcement of preoperative education on knowledge and recovery of patients having coronary artery bypass graft surgery. Heart Lung 1991; 20: 654–660.[ISI][Medline]

34. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67: 361–370.[ISI][Medline]

35. Moorey S, Greer S, Watson M et al. The factor structure of the Hospital Anxiety and Depression Scale in patients with cancer. Br J Psych 1991; 158: 255–259.[Abstract]

36. Cassileth BR, Zupkis RV, Sutton-Smith K et al. Information and participation preferences among cancer patients. Ann Intern Med 1980; 92: 832–836.[ISI][Medline]

37. Degner LF, Sloan JA. Decision making during serious illness: what role do patients really want to play? J Clin Epidemiol 1992; 45: 941–950.[ISI][Medline]

38. Butow PN, Dunn SM, Tattersall MHN et al. Patient participation in the cancer consultation: evaluation of a question prompt sheet. Ann Oncol 1994; 5: 199–204.[Abstract]

39. Brown R, Butow PN, Boyer MJ et al. Prompting patient participation in the cancer consultation: evaluation of a question prompt sheet and coaching in question asking. Br J Cancer 1999; 80: 242–248.[ISI][Medline]

40. Dunn SM, Patterson PU, Butow PN et al. Cancer by another name: a randomized trial of the effects of euphemism and uncertainty in communicating with cancer patients. J Clin Oncol 1993; 11: 989–996.[Abstract]

41. SPSS for Windows: Base system user’s guide, Release 6.1. Chicago, IL: SPSS 1994; 828.

42. Ellis PM, Butow PN, Tattersall MHN et al. Accrual to clinical trials in breast cancer. Ann Sci Meeting Clin Oncol Soc Aust 1996: A12 (Abstr).

43. Siminoff LA, Fetting JH. Effects of outcome framing on treatment decisions in the real world: impact of framing on adjuvant breast cancer decisions. Med Decis Making 1989; 9: 262–271.[ISI][Medline]

44. Sheldon JM, Fetting JH, Siminoff LA. Offering the option of randomized clinical trials to cancer patients who overestimate their prognoses with standard therapies. Cancer Invest 1993; 11: 57–62.[ISI][Medline]

45. Fetting JH, Siminoff LA, Piantadosi S et al. Effect of patients’ expectations of benefit with standard breast cancer adjuvant chemotherapy on participation in a randomized clinical trial: a clinical vignette study. J Clin Oncol 1990; 8: 1476–1482.[Abstract]

46. Verheggen FW, Nieman F, Jonkers R. Determinants of patient participation in clinical studies requiring informed consent: Why patients enter a clinical trial. Patient Educ Couns 1998; 35: 111–125.[ISI][Medline]

47. Edwards SL, Lilford RJ, Hewison J. The ethics of randomised controlled trials from the perspectives of patients, the public and healthcare professionals. Br Med J 1998; 317: 1209–1212.[Free Full Text]

48. Johnson JD, Roberts CS, Cox CE et al. Breast cancer patients’ personality style, age, and treatment decision making. J Surg Oncol 1996; 63: 183–186.[ISI][Medline]

49. Fallowfield LJ, Jenkins V, Brennan C et al. Attitudes of patients to randomised clinical trials of cancer therapy. Eur J Cancer 1998; 34: 1554–1559.[ISI][Medline]

50. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987; 317: 141–145.[Abstract]

51. Fleissig A, Jenkins V, Fallowfield L. Results of an intervention to improve communication about randomised clinical trials of cancer therapy. Eur J Cancer 2001; 37: 322–331.[ISI][Medline]

52. Fender GRK, Prentice A, Gorst T et al. Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia Menorrhagia Education Study. Br Med J 1999; 318: 1246–1250.[Abstract/Free Full Text]

53. Brandberg Y, Bergenmar M, Michelson H et al. Six-month follow-up of effects of an information programme for patients with malignant melanoma. Patient Educ Couns 1996; 28: 201–208.[ISI][Medline]





This Article
Abstract
Full Text (PDF)
E-letters: Submit a response
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (6)
Disclaimer
Request Permissions
Google Scholar
Articles by Ellis, P. M.
Articles by Tattersall, M. H. N.
PubMed
PubMed Citation
Articles by Ellis, P. M.
Articles by Tattersall, M. H. N.