Patient and Physician Attitudes Toward Breast Cancer Clinical Trials: Developing Interventions Based on Understanding Barriers

original

contribution

Patient and Physician Attitudes Toward Breast Cancer Clinical Trials: Developing Interventions Based on Understanding Barriers Michelle E. Melisko,1 Fern Hassin,1 Lauren Metzroth,1 Dan H. Moore,1 Beth Brown,1 Kiran Patel,2 Hope S. Rugo,1 Debu Tripathy3 Abstract PURPOSE: Clinical trials are essential to develop and test novel therapies, yet only 2%-3% of women with breast cancer enroll. We sought to describe patient and physician barriers to trial participation and then implemented targeted interventions to increase awareness and interest in trial participation. Also, with increasing patient interest in complementary and alternative medicine (CAM) for cancer, we explored attitudes regarding CAM clinical trials. PATIENTS AND METHODS: Between 1997 and 2000, questionnaires were offered to patients with newly diagnosed or recurrent breast cancer and to physicians specializing in breast cancer. Programs aimed at patients and physicians from our geographic region to increase their support for breast cancer clinical trials were initiated in 1997. Correlation between perceived barriers and patient and physician demographics were explored. Reluctance to be randomized, extra time, and concerns about worse side effects with the experimental arm were the most significant patient barriers. Physician barriers included randomization, extra staff time, and increased costs of enrollment. Patients and physicians approved of studying CAM in clinical trials, with different scores based on age and type of practice. Physicians and patients developed more favorable views of clinical trials between 1997 and 2000. RESULTS: Although many barriers still exist, this study suggests that attitudes toward clinical trials are evolving and significantly affected by patient age and stage of disease. Because different patients and some different physicians were surveyed, it is difficult to conclude that the changes occurred as a result of the interventions. CONCLUSION: Future efforts to improve enrollment should focus on patients’ individual concerns and the uneasiness with the randomization. Clinical Breast Cancer, Vol. 6, No. 1, 45-54, 2005 Key words: Participation, Patient education, Randomization

Introduction Clinical trials are necessary to develop and understand new and more effective breast cancer prevention, diagnostic, and treatment strategies. As interventions are being tested in lower-risk cohorts of patients, larger sample sizes are required to demonstrate small incremental improvements in outcome. 1University

of California, San Francisco Palo Alto, CA 3University of Texas Southwestern Medical Center, Dallas 2Telik,

Submitted: Dec 12, 2003; Revised: Apr 7, 2004; Accepted: Apr 8, 2004 Address for correspondence: Debu Tripathy MD, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-8852 Fax: 214-648-1955; e-mail: [email protected]

In addition, increasing interest in complementary and alternative medicine (CAM) has led to the incorporation of these therapies into clinical trials to validate their efficacy. However, there has been little research exploring patients’ and physicians’ attitudes toward clinical trials involving CAM. During recent decades, the increase in incidence of breast cancer has drawn attention and increased funding to the areas of screening and treatment. Despite an increase in the overall number of new clinical research initiatives and trials open to accrual, only 2%-3% of women with breast cancer enroll in clinical trials, and an even smaller fraction enroll on adjuvant therapy studies.1 Even at academic institutions with a commitment to clinical research, only 10%-15% of patients with breast cancer are enrolled in a clinical trial.2

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Clinical Breast Cancer April 2005 • 45

Understanding Attitudes Toward Breast Cancer Clinical Trials Current clinical trial design is problematic in that only 20%40% of patients with cancer presenting to community or academic centers are eligible for trials.3 Patients who have received a great number of previous treatments or who have no sites of measurable disease are often excluded from clinical trials. Advanced age and poor performance status are also common reasons for trial ineligibility.4 Although patients generally accept the need for clinical trials, many women hold negative views of clinical trial research, particularly the randomization process.5 Other factors that have been previously identified as barriers to enrollment include a patient’s desire for a treatment different from that offered in a clinical trial and difficulties related to geographic distance from the cancer center where the trial was offered.6 Conversely, altruism and the desire to foster the progress of medical research have been shown to facilitate a woman’s decision to enter a breast cancer clinical trial. Furthermore, the belief that clinical trials may allow access to superior care has been found to be a motivating factor to participate.7 There is additional evidence showing that physicians’ bias against the enrollment of patients into a clinical trial is a major inhibitor to subject accrual.8 Lack of knowledge of clinical trials,9 fear of losing patients,10 and concern regarding the toxicity of regimens11 have been demonstrated to impede recruitment of patients into clinical trials. Other issues that have been identified include time constraints, liability concerns, ethics of patient care, and patient inconvenience.12 In addition, personal characteristics of medical oncologists and surgeons, including age, practice setting, and membership in a cooperative group, have also been shown to influence their support for patient enrollment in clinical trials.13 To develop future outreach and educational tools to increase clinical trial enrollment, we sought to better understand the factors that influence trial participation in these patients when they would typically be eligible for trials (when they are about to start therapy or change treatments). We also explored impediments to clinical trial enrollment created by physicians providing specialty care in breast cancer in our region. After initiating programs in our breast cancer community to increase awareness and stress the importance of clinical trials, we evaluated the changes in attitudes towards clinical trials that had occurred over a 3-year period.

Patients and Methods All patients seen at a multidisciplinary evaluation and treatment facility were tracked based on their disease status by reviewing provider notes and International Classification of Diseases–9 codes entered from clinic visits. Patients who had received a new diagnosis of breast cancer or who were experiencing a recurrence of breast cancer or progression of metastatic disease were approached to participate in this survey. This research study and the surveys used were reviewed and approved by the University of California San Francisco (UCSF) Committee on Human Research, and informed consent was received on all participants. Participants were recruited by 2 clinical research assistants at the time of

46 • Clinical Breast Cancer April 2005

their appointment and were asked to complete the questionnaire during their clinic visit. In a few cases, women completed the questionnaire over the phone or returned it by mail if they were unable to complete it in clinic. The patient questionnaire consisted of 28 items separated into domains including access to clinical trial information, safety issues, logistics (including time, cost, and travel), confidentiality, attitude toward randomization, and feelings about investigation of CAM. Patient characteristics studied included year of diagnosis, age, race, educational level, stage of disease, marital status, and family history of breast cancer. Responses were answered on a 5-point Likert scale, with 1 representing “strongly disagree with statement” and 5 representing “strongly agree with statement.” The questionnaire was initially piloted in focus groups that included patients with breast cancer and advocates. Two questions were not included in the survey distributed in 2000 because many patients completing the survey in 1997 found them confusing or did not respond to them for personal reasons (Appendix 1). Responses were entered into a database and SAS was used for statistical comparisons. Mean Likert scores and standard deviations for the 2 study years were compared using Student t tests. Linear regression and analysis of variance were used to study the effects of patient characteristics on Likert response scores. Because > 100 statistical comparisons were made, we report the overall number statistical tests with P < 0.05 and with P < 0.01 and compare these numbers with the numbers expected by chance under the assumption that patient characteristics had no effect on the response scores. Between 1997 and 2000, a number of targeted interventions were undertaken to address the impediments identified based on the survey results from 1997. Patient interventions included the Bay Area Breast Cancer Forum, which was initiated in January 1997. This monthly event hosts approximately 50 people for dinner and discussion on subjects of interest in breast cancer research. Also, brochures and a “Breast Cancer Research Awareness Poster” were displayed at mammography suites and cancer resource centers. They were also mailed to the offices of oncology surgeons, primary care physicians, and gynecologists in the Bay Area. In December 1998, a moderated panel discussion was held to address barriers to clinical trials for minority and underserved populations. This program, titled “Beating the Odds of Breast Cancer: How Can Research Help?”, was videotaped and distributed to 12 hospitals and university resource centers in the Bay Area. Further, our clinic Web site was developed and updated to include clinical trial information, a breast cancer glossary, a clinic newsletter, and links to other relevant sites. The Web site also contains minutes from the Forum meeting, topics for future meetings, and general instructions about navigating through treatment at the Breast Care Center. In addition to the patient survey, we recruited physicians specializing in the care of patients with breast cancer in the Bay Area to complete a separate 31-item survey (Appendix

Michelle E. Melisko et al 2). Physicians from private and academic centers and from the specialties of medical, surgical, and radiation oncology, pathology, and radiology were contacted by mail. Using a 5-point Likert scale, clinicians were asked to rate the significance of previously identified concerns about clinical trials including impact on clinical practice, costs to the patient, and protocol merit. Information about demographics, subspecialty, and practice setting was also collected. Between 1997 and 2000, several interventions were targeted to physicians involved in the care of patients with breast cancer. Physicians received invitations to the monthly Breast Cancer Forum and were encouraged to attend tumor board at the UCSF Breast Care Center, where they could present challenging cases and obtain updates on clinical trials and new research activities.

Table 1 Patient Characteristics Characteristic

1997

2000

52.9 Years

53.2 Years

Married

53%

56%

White

88%

81%

Family History of Breast Cancer

39%

28%

Premenopausal

45%

42%

Some high school

6%

0

High school graduate

12%

15%

Some college/technical school

19%

14%

Results

College graduate

36%

34%

Patient Responses

Graduate school

25%

36%

In situ

2%

4%

I

25%

41%

II

58%

28%

III

5%

14%

IV

7%

13%

The survey was completed by 150 patients in 1997 and another group of 147 in 2000, although not all questions were completed by all responders. The refusal rate to respond to the questionnaire was < 5%. Mean age of the respondents was 53 years. Most women completing the survey in 1997 and 2000 had stage I/II cancer (Table 1). There were no significant differences in the demographics between those who responded in 1997 and in 2000. A number of qualitative beliefs that might act as barriers to participation in clinical trials were observed among respondents in 1997 and 2000 (Figure 1). The strongest barrier was unwillingness to be randomized (mean score of 4.3 ± 1 of 5 over both years of the study). The second strongest barrier was concern about extra time related to more tests and doctor visits in a clinical trial (mean score, 3.9 ± 1.2). Other barriers included inability to choose own treatment arm in a CAM trial (3.7 ± 1.4), concern that randomized treatment might not be as good as regular treatment (3.6 ± 1.2), and the possibility of worse side effects with the new experimental drug (3.3 ± 1.1). Attitudes toward CAM were generally favorable. Patients agreed that CAM should be studied (3.5 ± 1.0) and that clinical trials can combine CAM and conventional medicines (3.4 ± 0.9). In addition, patients disagreed that clinical trials of CAM would limit their future treatment options (1.7 ± 1.0) and that a clinical trial would be a constant reminder of their breast cancer (1.8 ± 1.2). The average score including all 25 questions was 2.80 ± 0.13 in 1997 and 2.92 ± 0.13 in 2000 (P = 0.51), where a higher score represents more agreement with each statement and a more positive attitude toward clinical trials. Although some differences in responses to individual questions were observed between 1997 and 2000, none were significant at P < 0.01. Figure 2 illustrates the changes in scores between 1997 and 2000. Patients continued to have concern about the extra time involved in participating in a clinical trial (mean agreement, 3.8 in 1997 vs. 4.1 in 2000; P = 0.02 for the difference). However, respondents in 2000 were more likely than those in 1997 to agree with the statement that

Mean Age

Education Level

Disease Stage

they had sufficient information about clinical trials to decide whether to participate (mean agreement, 1.8 in 1997 vs. 2.6 in 2000; P = 0.01 for the difference). A number of correlations were apparent when responses were broken down by age, stage of cancer, level of education, ethnicity, and family history of breast cancer. Altogether, 135 statistical tests were conducted (27 questions, 5 tests per question) in this exploratory search for associations. With such a large number of associations tested, 6.75 could be found positive by chance alone at a P < 0.05 level, and 1.35 could be positive by chance alone at a P < 0.01 level. However, we found 18 associations at a P < 0.05 level and 7 associations at a P < 0.01 level. Transportation, childcare costs, and the extra loss of income represented greater impediments to a clinical trial in younger women than in older women (P = 0.01). Compared with younger patients, older patients believed that alternative therapy was still too unknown to be tested in clinical trials (P < 0.01). Compared with patients with more advanced-stage disease, those with earlier-stage disease were more concerned that participating in a clinical trial would interfere with choosing their own treatments (P = 0.002). There was also a trend for patients with earlier-stage disease to feel a loss of control over their medical decisions if enrolled in a clinical trial (P = 0.0496). Nonwhite patients and women with less education were more likely than white patients or those with more education to think that a clinical trial was not right for them if their physician did not bring it up first (P = 0.002 for edu-

Clinical Breast Cancer April 2005 • 47

Understanding Attitudes Toward Breast Cancer Clinical Trials Figure 1 Patient Attitudes Based on Mean Questionnaire Score Strongly Disagree

Neutral

Strongly Agree

Don't want to be randomized Extra time needed for trial On CAM trial, can't choose treatment Randomized treatment worse CAM should be studied Trial can test CAM Can see regular doctor Trial drug has more side effects Extra expenses on trial More side effects on trial Loss of confidentiality on trial Better QOL on trial Trial not right if doctor doesn't refer More stress on trial CAM too unknown Questions not answered on trial No control on trial Trial info available on Internet Doctor may not want trial New treatment on trial not better Treatment not delayed on trial Patient has enough info CAM trial a bad decision Trial a constant reminder of cancer CAM limits future treatment 1

2

3

4

5

Mean Likert scores and 95% confidence interval.

cation, P = 0.0005 for race). Patients with a family history of breast cancer were less likely than those with no family history to believe that participation in a clinical trial would be a constant reminder of their breast cancer (P = 0.0025). They were also less likely to think that participation in a study of alternative medicines would limit their choices for regular therapy in the future (P = 0.0016).

Physician Responses Surveys were completed by 68 of 150 physicians in 1997 and 59 of 160 physicians in 2000. Characteristics of the physicians, including age, subspecialty, and academic or Health Maintenance Organization (HMO) affiliation, are shown in Table 2. Review of responses from physicians’ surveys from 1997 and 2000 revealed several general themes (Figure 3). In

48 • Clinical Breast Cancer April 2005

contrast to the patient survey, a higher score in the physician survey indicated a barrier to clinical trial participation. Physicians from both years agreed with the statement that patients do not want to be randomized (mean agreement, 4.1 ± 1.1) and that enrolling patients in clinical trials involves extra staff time and adds cost to the practice (mean agreement, 3.8 ± 1.4). Physicians also agreed with the statement that clinical trials may be too inconvenient and time-consuming for some patients (mean agreement, 3.5 ± 1.4). Based on the findings of the 2 surveys, physicians seemed to develop more favorable views of clinical trials between 1997 and 2000 (Figure 4). The average response score to all 31 questions identifying barriers to clinical trials was 2.78 ± 0.09 in 1997, which was reduced to 2.46 ± 0.09 in 2000 (P = 0.02 for the difference). In 2000, physicians cited less con-

Michelle E. Melisko et al Figure 2 Patient Preference Score Changes Changes In Mean Score Between 1997 and 2000 More Agreement

Less Agreement

Don't want to be randomized Extra time needed for trial On CAM trial, can't choose treatment Randomized treatment worse CAM should be studied Trial can test CAM Can see regular doctor Trial drug has more side effects Extra expenses on trial More side effects on trial Loss of confidentiality on trial Better QOL on trial Trial not right if doctor doesn't refer More stress on trial CAM too unknown Questions not answered on trial No control on trial Trial info available on Internet Doctor may not want trial New treatment on trial not better Treatment not delayed on trial Patient has enough info CAM trial a bad decision Trial a constant reminder of cancer CAM limits future treatment

–0.6

–0.4

–0.2

cern that clinical trials may have an experimental arm with a worse outcome or more toxicity (mean agreement, 3.0 in 1997 vs. 2.4 in 2000; P = 0.017). There was less agreement that clinical trials were too stressful for their patients (mean agreement, 2.7 in 1997 vs. 2.3 in 2000; P = 0.03), and that clinical trials involving CAM would interfere with other aspects of the patient’s care (mean agreement, 2.9 in 1997 vs. 2.3 in 2000; P = 0.04). Also, physicians completing the survey in 2000 were less likely to agree with the statement that dissemination of information on clinical trials was inadequate (mean agreement, 2.4 in 1997 vs. 1.9 in 2000; P = 0.02). We also explored associations between physician responses and their age, specialty, and practice setting. We found 22 at a P < 0.05 level (4.6 expected by chance), including 10 at a P < 0.01 level (0.9 expected by chance). Older physicians

0

0.2

0.4

0.6

0.8

1

were more likely than younger ones to agree that the standard or control arm in clinical trials may offer inadequate therapy (mean score, 2.8 for age < 50 years vs. 3.5 for age > 50 years; P = 0.005 for the difference). Older physicians were more concerned than younger ones about short- and long-term side effects of a clinical trial (mean score, 1.9 for age < 50 years vs. 2.6 for age > 50 years; P = 0.04) and were more likely to believe that a clinical trial might interfere with other aspects of care (mean score, 2.0 for age < 50 years vs. 2.8 for age > 50 years; P = 0.02), particularly if the trial involved CAM (mean score, 2.1 for age < 50 years vs. 2.9 for age > 50 years; P = 0.01). In contrast, younger physicians were much more likely than older ones to want alternative therapies to be studied in a clinical trial (mean score, 3.2 for age < 50 years vs. 2.4 for age > 50 years; P = 0.0005).

Clinical Breast Cancer April 2005 • 49

Understanding Attitudes Toward Breast Cancer Clinical Trials Table 2 Physician Demographics Demographic

1997

2000

30-39 Years

11.8%

11.9%

40-49 Years

42.7%

30.5%

50-59 Years

30.9%

40.7%

> 60 Years

14.7%

17%

Medical oncology

67.7%

42.4%

Surgery

14.7%

23.7%

Radiation oncology

11.8%

11.9%

Other

5.9%

22%

Health maintenance organization

14.9%

8.8%

Academic

26.9%

50.9%

Hospital

13.4%

8.8%

Private

44.8%

31.6%

Age

Practice Type

Practice Setting

Compared with other physicians surveyed, medical oncologists were more likely to think that eligibility criteria were too strict (P = 0.0001) and that the clinical trial process was too slow to answer questions as new treatment options emerge (P = 0.0226). Medical oncologists also expressed concern that some patients’ beliefs in CAM were too strong for them to participate in a clinical trial evaluating these therapies (P = 0.0015). Interestingly, although surgeons were most likely to believe that alternative therapies should be studied (P = 0.006), they also were also most likely to say that they did not have enough information readily available on clinical trials to offer them to all eligible patients (P = 0.0022). Medical oncologists and radiation oncologists agreed that enrolling patients in clinical trials involved extra staff time and cost (P = 0.0008). Differences were also noted based on physicians’ practice setting. Private physicians were more likely to think that clinical trials might be too stressful for their patients (P = 0.0058) and that clinical trials might delay therapy for breast cancer (P = 0.0080).

Discussion This study confirms that patients with breast cancer and their care providers have many of the same attitudes toward clinical trial participation that have been described in general oncology populations. The randomization process stands out as the most dramatic obstacle to participation in clinical trials. Similarly, this study also verified that patients have significant concerns about the potential for more toxicity related to treatment in a clinical trial. Loss of income and the

50 • Clinical Breast Cancer April 2005

extra time required for tests and doctor visits negatively affect a woman’s decision to participate in a clinical trial, especially among younger patients. Previous studies have suggested that poor women and women of racial minorities are hesitant to participate in clinical trials because of concerns over efficacy of the experimental agent.14 In contrast, this survey revealed only minor differences in beliefs regarding clinical trials between white and nonwhite patients. Patients completing this questionnaire tended to have a high level of education, and the knowledge barriers that have been previously identified for nonwhite patients may not have played a significant role in the attitudes of our patients. Similar findings have also been reported by Advani et al, who noted that education and income, rather than race, were the major barriers to clinical trial participation.15 An intriguing finding of this trial was that a patient’s stage of disease impacted feelings regarding clinical trials, and patients with earlier-stage disease were more concerned by loss of control. One explanation could be that patients with advanced or metastatic disease have fewer options and therefore are willing to consider an experimental therapy. Alternatively, they may have more experience with the medical system and may have previously participated in a trial. Another survey has shown that patients with previous clinical trial experience are more likely to agree to participate in randomized trials.16 Conversely, women with an actual diagnosis of breast cancer have been found to be less willing to participate in a clinical trial than women who are undergoing screening mammography or diagnostic assessment.17 This survey indicated that breast cancer specialists face similar barriers to trial enrollment as general medical and surgical oncologists.18 Increased availability and simplification of protocols may be necessary to improve accrual among private physicians and physicians who work in HMOs. Because the majority of patients with breast cancer (especially those with early-stage disease receiving straightforward adjuvant therapy) are treated in the community and not at academic centers, it will be increasingly important to involve these practice sites in clinical trials. This study represents one of the first explorations into patient and physician attitudes toward clinical trials that involve CAM. Obstacles to recruitment into a breast cancer CAM trial have been previously reported,19 but our study adds new information. Most women and physicians believed that CAM should be studied, but older and nonwhite patients believed that these treatments were still too unknown. This may reflect a lack of exposure to information about these types of therapies, which are often publicized on the Internet or through word of mouth. A previous survey of medical oncologists in Japan reported a high level of skepticism toward the efficacy of CAM products against cancer.20 A significant number of these oncologists lacked reliable information on CAM therapies and were concerned about the possibility of drug interactions between standard and CAM therapies. In the future, with increased knowl-

Michelle E. Melisko et al Figure 3 Physician Attitudes Based on Mean Questionnaire Score Strongly Disagree

Neutral

Strongly Agree

Don't want to be randomized Extra time needed for trial On CAM trial, can't choose treatment Randomized treatment worse CAM should be studied Trial can test CAM Can see regular doctor Trial drug has more side effects Extra expenses on trial More side effects on trial Loss of confidentiality on trial Better QOL on trial Trial not right if doctor doesn't refer More stress on trial CAM too unknown Questions not answered on trial No control on trial Trial info available on Internet Doctor may not want trial New treatment on trial not better Treatment not delayed on trial Patient has enough info CAM trial a bad decision Trial a constant reminder of cancer CAM limits future treatment 1

2

3

4

5

Mean Likert scores and 95% confidence interval.

edge of CAM therapies and their use in conjunction with more traditional treatments, patients and physicians will have more confidence in participating in trials studying these therapies. One very promising aspect of this study was that certain attitudes toward clinical trials seemed to improve for patients and physicians between 1997 and 2000. Patients and physicians reported improved access to information about clinical trials in 2000 compared with 1997. In addition, physicians had less concern that trials would be stressful, limit patients’ treatment options, and interfere with other aspects of patient care. However, there are still challenges to be met because certain groups of physicians still believed they might not have enough information about eligibility and the specifics of clinical trials to enroll their patients.

It is not clear whether our interventions and outreach played a role in this improvement or whether the general public’s awareness of the importance of clinical trials has independently increased over time. Several groups have recently reported the effect of their interventions to improve clinical trial enrollment. One study randomized patients with breast cancer to receive usual information from their oncologists regarding treatment options or usual information plus an educational booklet explaining the need for and the conduct of clinical trials to determine whether increased information would increase participation.21 Interestingly, they reported that patients who received the booklet were significantly less likely to consider clinical trial participation. In another community based program in eastern North Carolina, outreach efforts similar to those employed in our study

Clinical Breast Cancer April 2005 • 51

Understanding Attitudes Toward Breast Cancer Clinical Trials Figure 4 Physician Preference Score Changes Changes In Mean Score Between 1997 and 2000 Less Agreement

Don't want to be randomized

More Agreement

Extra time needed for trial On CAM trial, can't choose treatment Randomized treatment worse CAM should be studied Trial can test CAM Can see regular doctor Trial drug has more side effects No Change

Extra expenses on trial More side effects on trial Loss of confidentiality on trial

No Change

Better QOL on trial Trial not right if doctor doesn't refer More stress on trial CAM too unknown Questions not answered on trial

No Change

No control on trial Trial info available on Internet Doctor may not want trial New treatment on trial not better Treatment not delayed on trial Patient has enough info CAM trial a bad decision Trial a constant reminder of cancer CAM limits future treatment –0.8

–0.6

–0.4

did not lead to significant changes in awareness of clinical trial opportunities or to increased clinical trial participation among rural patients over a 3-year period.22 This lends further support to our belief that a better understanding of barriers to participation, which may be unique to a specific population, may lead to more successful interventions. Increased participation in clinical trials in breast cancer is crucial to the advancement of new therapies. This study helps elucidate the barriers to participation and suggests that interventions and outreach can influence patients’ attitudes, albeit in modest ways. This survey also suggests that the decision to participate is strongly influenced by factors related to a patient’s age and life circumstances. Future interventions should be directed toward simplifying participation in clinical trials by limiting additional costs, physician visits, and time. Because the randomization process remains a fundamental barrier, it is crucial

52 • Clinical Breast Cancer April 2005

–0.2

0

0.2

0.4

0.6

that physicians discuss trials thoroughly with their patients and assure them that the control arm is carefully chosen to represent the best available standard of care. Furthermore, it will be the challenge of the medical research community to devise strategies other than randomization that will preserve the scientific principle of a controlled trial.

Acknowledgements This research was supported in part by DOD–USAMRMC DAMD17-96-1-6260 and the UCSF Breast Cancer Spore (NCI P50 CA 58207).

Appendix 1: Patient Questionnaire 1.

I have enough information about clinical trials to make a good decision about being in a trial.

Michelle E. Melisko et al 2.

3. 4. 5. 6. 7. 8. 9. 10.

11.

12.

13. 14.

15.

16.

17. 18.

19.

20. 21. 22.

Clinical trial information is available on the Internet, and I would use it to find out more about available trials. Being in a clinical trial would not limit my choices for future treatment.* I will get my needed treatment as soon as possible if I am in a trial. In a clinical trial, I am able to see my regular doctors. If my doctor does not suggest looking into clinical trials, they are probably not right for me. My doctor may not want me to participate in a trial. I may not have all my questions answered if I am in a trial. If I am in a trial, I may have to spend extra time having more tests and doctor visits. I may have to spend more time and money on transportation and childcare and may lose income due to time away from work if I participate in a clinical trial. If I am in a clinical trial, my insurance company would cover the cost of my treatment and I would not have to pay more money myself.* I may have more harmful side effects, or become sicker, if I am in a clinical trial than I would with standard treatment. Being in a clinical trial would cause me more mental stress. I would not want to participate in a clinical trial because it would be a constant reminder that I have breast cancer. If I am in a trial, other parts of my overall wellbeing and quality of life (QOL) would not be addressed as well as they would be with standard treatment. New drugs and treatments for breast cancer may not be better than older, standard drugs and treatments. If I am in a trial that looks at a new drug, I might have worse side effects. If I participate in a randomized study, where I am assigned to one of 2 or more treatments by chance, my treatment would not be as good as regular treatment. I would like to know what treatment I am signing up for and therefore would not want to be randomized, or assigned to one of two treatments by chance. I would have no control over my medical decisions if I participated in a clinical trial. Participating in a clinical trial would make my medical records less confidential. The area of alternative medicine (such as wholistic, homeopathic or herbal medicines) should be studied in clinical trials.

23. There is not enough known about alternative medicine for me to participate in a trial testing alternative medicine. 24. I would not want to be in a study of alternative medicine where I would not be able to choose my own treatment. 25. A clinical trial can test the negative effects of alternative medicine combined with regular medicine. 26. A study of alternative medicine would not limit my choices for regular therapy in the future. 27. If I was in a study of alternative medicine, my doctors, friends and family may think it was a bad decision. 28. I would like to participate in a clinical trial but would not be able to because English is not my native language. * Omitted from questionnaire in 2000 because of incomplete number of responses in 1997 survey.

Appendix 2: Physician Questionnaire 1. The control, or standard, arm on a controlled trial may offer inadequate therapy in some patients. 2. Eligibility criteria are too restrictive. 3. Controlled trials may contain an experimental arm that is likely to produce a worse outcome or have worse toxicity without any benefit. 4. Important areas of uncertainty in breast cancer treatment are not addressed by clinical trials. 5. New approaches being studied in clinical trials are not fundamentally different from current standard of care and are not likely to show clinical improvements in breast cancer. 6. The clinical trial process is too slow to answer questions as treatment options and new agents emerge. 7. New agents may have unacceptable short and long term side effects and clinical trials are not designed to properly assess these side effects. 8. New agents may be found to have very small benefit at costs that neither patients nor the health care system in general can afford. 9. Clinical trials do not study cost-effectiveness. 10. Patients may already want treatment with 1 of the arms and would not want to be randomized. 11. Clinical trials may be too inconvenient and time consuming for certain patients. 12. The clinical trial process is too stressful for the patient. 13. Clinical trials cost too much for the patient. 14. Enrolling a patient on a trial can interfere with other aspects of medical care. 15. Enrolling a patient on trial may delay needed therapy for breast cancer.

Clinical Breast Cancer April 2005 • 53

Understanding Attitudes Toward Breast Cancer Clinical Trials 16. Participation in a clinical trial may cause the patient to lose follow-up with or change from the referring specialist and primary care providers. 17. A patient’s QOL may not reliably be measured in a clinical trial. 18. Participation in a clinical trial assessing a new agent may limit future treatment options. 19. Patients participating in clinical trials may not directly benefit from them. 20. Consent forms and protocols may be difficult for many patients to understand. 21. Consent forms may be misleading to patients and may not discuss standard treatment options. 22. Many patients want to participate, but are not eligible for any clinical trials. 23. Enrolling a patient on a trial can take extra staff time and cost to the practice. 24. I do not have enough information on clinical trials readily available to offer trials to all eligible patients. 25. The area of alternative medicine (such as wholistic, homeopathic, or herbal medicines) should be studied in clinical trials. 26. Not enough is known about alternative medicine to yet justify clinical trials in this area. 27. Some people’s beliefs in alternative medicine are too strong for them to participate in clinical trials examining this approach. 28. Clinical trials may not be able to test standard approaches in conjunction with alternative medicine. 29. Clinical trials in alternative medicine may interfere with other aspects of patient treatment and care. 30. Participation in a clinical trial with alternative medicine may cause a loss of credibility to the patient and patient’s caregivers. 31. Dissemination of information on clinical trials is inadequate.

54 • Clinical Breast Cancer April 2005

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