J Clin Oncol 24: by American Society of Clinical Oncology INTRODUCTION

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1 VOLUME 24 NUMBER 25 SEPTEMBER JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Impact of a Multi-Disciplinary Patient Education Session on Accrual to a Difficult Clinical Trial: The Toronto Experience With the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial Kris Wallace, Neil Fleshner, Michael Jewett, Joan Basiuk, and Juanita Crook From the Departments of Radiation Medicine and the Division of Urology and Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Canada. Submitted March 1, 2006; accepted July 6, Authors disclosures of potential conflicts of interest and author contributions are found at the end of this article. Address reprint requests to Juanita Crook, MD, FRCPC, Princess Margaret Hospital, 610 University Ave, Toronto, Canada, M5G 2M9; juanita.crook@rmp.uhn.on.ca by American Society of Clinical Oncology X/06/ /$20.00 DOI: /JCO A B S T R A C T Purpose Random assignment to clinical trials involving different treatment modalities can be difficult. We describe our experience with the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT; ACOSOG Z0070 NCIC PR10), a randomized trial for early-stage prostate cancer comparing radical prostatectomy (RP), and brachytherapy (BT). A multidisciplinary educational session was developed to improve patient understanding of treatment options and to facilitate accrual. Patients and Methods Prostate cancer referrals were screened and men who met favorable risk criteria (T1c/T2a, prostate-specific antigen [PSA] 10 ng/ml, Gleason 6) were invited to a structured education session before a specialty consultation. Men and their partners viewed the SPIRIT informedconsent video and heard from a cancer patient who described his participation in a randomized trial. Then, a urologist and radiation oncologist together compared and contrasted RP and BT to establish the rationale for the trial. Results In May 2002, SPIRIT opened for accrual and was endorsed by the University Health Network urologists and radiation oncologists. The first 27 eligible patients were approached about SPIRIT, consulted both specialties, and viewed an educational video. No patients consented. The multidisciplinary education session was then introduced. Forty-seven education sessions with 263 patients resulted in 34 consents. Of 203 patients who were suitable for the study but declined random assignment, 62 chose surgery, 94 chose brachytherapy, three patients chose external radiotherapy, and 11 chose no treatment. Consent rates for eligible and suitable patients were one in six. Conclusion Men who understand their treatment options and trial rationale as presented jointly by representative specialists from competing treatment modalities may be better equipped to make an informed decision and are more likely to consent to random assignment. J Clin Oncol 24: by American Society of Clinical Oncology INTRODUCTION Of the 250,000 men diagnosed with prostate cancer per annum in North America, approximately 60% have early-stage favorable disease. Many make treatment decisions based on anecdotal information or unsubstantiated opinion. No randomized clinical trials have previously addressed relative efficacy or quality of life following radical prostatectomy and brachytherapy. 1-5 Therefore, SPIRIT (Surgical Prostatectomy versus Interstitial Radiation Intervention Trial; American College of Surgeons Oncology Group [ACOSOG] Z0070 National Cancer Institute of Canada [NCIC] PR10) was designed to randomly assign men with early-stage prostate cancer to one of these two options. The trial received Cancer Therapy Evaluation Program (CTEP; National Cancer Institute, Bethesda, MD) approval in 2002 and subsequently opened in 31 centers across North America. ACOSOG developed and distributed a patient education video and brochure. As initial experience with accrual was disappointing, we developed a small-group patient education session to provide the balanced information required for informed decision. Sessions were held weekly for new patients with a goal to compare radical prostatectomy and 4158

2 Toronto Experience With SPIRIT brachytherapy in a multidisciplinary setting, to establish the rationale for randomized trials in general, and to introduce SPIRIT. PATIENTS AND METHODS SPIRIT was launched in May 2002 at the Princess Margaret Hospital (Toronto, Canada). To identify eligible patients, urology and brachytherapy prostate cancer referrals were screened by the clinical research associate (CRA). Eligible patients had Gleason score 6, prostate-specific antigen (PSA) 10.0 ng/ml, prostate transrectal ultrasound (TRUS) volume 60 cc, and biopsy less than 120 days previously. The CRA met individually with each patient to introduce the concept of SPIRIT and view the informed consent video. In addition, each patient was approached by their urologist and/or radiation oncologist about the study. Over 3 months, 27 patients viewed the video but none consented to random assignment. Review of this experience in a multidisciplinary setting resulted in the institution of education sessions. The 90-minute education session was facilitated by the CRA for a maximum of 10 patients. Patients were advised to bring a companion and to attend before their individual consultations with specialists. 6 Chairs were arranged in the session in a semi-circle to encourage interactive dialogue. At the initial sessions, after screening the 25-minute SPIRIT Informed Consent Video (ACOSOG), a prostate cancer survivor and clinical trial participant shared his view of clinical trials. In later sessions, a SPIRIT participant discussed his decision-making process with the group. The intention was not to focus on anecdotal details, but to communicate the reasons for his decision and any benefits he felt he had gained. Next, the urologist and radiation oncologist joined the session. Using a PowerPoint (Microsoft Corporation, Redmond, WA) presentation as a guide, the urologist and radiation oncologist jointly compared and contrasted their modalities and introduced the concept of a randomized trial. The emphasis was on understanding surgery and brachytherapy, with randomization presented as a third option. The session addressed procedure details and recovery, urinary and erectile function, PSA response, and salvage therapy. Only if deemed equally suitable for surgery and brachytherapy, would SPIRIT be an option for the patient. The final portion of the session was interactive. Questions were encouraged, although those of a personal nature were deferred until the individual consultation sessions. Comfort with both treatment options and a willingness to undergo either treatment was necessary for consent. While attendees completed a questionnaire to evaluate the session, the CRA ensured that each attendee had a clear schedule of upcoming appointments and distributed the SPIRIT brochure (ACOSOG) and PowerPoint outline. All handouts and questionnaires received institutional ethics approval. Following closure of SPIRIT, 190 session attendees were contacted by the CRA to assess treatment satisfaction and to record demographics. RESULTS Before closure of SPIRIT by ACOSOG in April 2004, 263 patients attended 47 sessions, resulting in 34 consents and 32 random assignments. One patient who consented was deemed ineligible before random assignment, and the final consent occurred on the day of study suspension. Forty-five session attendees were assessed as unsuitable for SPIRIT, usually because of voiding dysfunction which rendered brachytherapy inadvisable, or medical comorbidities that could complicate surgery. Fifteen patients were still undecided at study closure. Of the 203 patients who were suitable but declined SPIRIT, 62 chose surgery, 94 chose brachytherapy, three chose external radiotherapy, and 11 opted for watchful waiting. The consent rate for eligible and suitable patients from the launch of the educational intervention was one in six. The questionnaire to assess the education intervention from the patient s perspective was introduced in May 2003 (Appendix). From 27 sessions, 182 questionnaires were completed. Patients ranked statements on a scale of increasing agreement from 1 to 5. The global response was very positive, with 79% agreeing or strongly agreeing that their understanding of prostate cancer (median, 5; mean, 4.15) and their treatment options (median, 5; mean, 4.09) had improved. Similarly, the information provided was deemed helpful in making a decision about treatment (median, 5; mean, 3.96). Following closure of the trial, the CRA contacted 190 attendees to assess their treatment satisfaction and demographics (SPIRIT, 34; radical prostatectomy [RP] choice, 62; brachytherapy [BT] choice, 94). There were no significant differences among the three groups concerning urban/rural residence (P.119), education level (P.155), marital status (P.75), or treatment satisfaction (P.61; Table 1). Specifically, 82% of those patients who accepted random assignments were city dwellers, 85% were married, 79% had postsecondary education, and 94% would recommend their treatment to a friend. Treatment satisfaction was very high in all three groups. DISCUSSION Many factors influence clinical trial accrual. In the palliative setting, exhaustion of standard modalities may position a clinical trial as a last hope. Clearly this does not apply to early-stage curable disease, for which many options exist. To consider a randomized trial, patients must understand their options, the pros and cons of each option, and the reason for the trial. Accrual will result if the patient and their family perceive that the treatments being compared are not dissimilar, and/or if patients are equally comfortable with either option. Many patients would like to benefit others in the future, 7 if they can do so without risk to themselves. Trust in the medical team and a thorough understanding of the issues are essential Demographic characteristics that have been reported to be associated with a willingness to participate in clinical trials are older age, male sex, lower educationl level, and lower socioeconomic background. 6,12,13 Llewellyn-Thomas et al 14 reported that patients with greater knowledge about a trial were less willing to participate. In contrast, Ellis 15 found that poor understanding of the concept of clinical trials, and not the details of the trial itself, was a barrier. A cross-sectional survey of a breast cancer screening clinic showed that younger women with a better understanding of the issues, who wanted an active role in decision making, were more likely to participate. Trial endorsement by a high-profile national organization also increased participation. Our experience with SPIRIT would support the view that greater knowledge and understanding have a positive effect on accrual. None of the team members associated with the SPIRIT education sessions have a background in patient education, nor was advice sought from an educator. Our goal was to ensure consistency in the information presented by the disciplines involved. Catt et al 16 have shown that consistency of approach may be assumed among members of a health care team but might not be perceived by the patient. Patients often ask the same questions to multiple health care professionals, either because they forget, or did not understand, or are seeking reassurance. Recollection of only parts of an explanation may give a false impression. We felt it was essential that the specialty consultants be available

3 Wallace et al Table 1. Demographics and Follow-Up Satisfaction With Treatment Decision, Based on Men Having Brachytherapy (n 94), Radical Prostatectomy (n 62), and Consenting to SPIRIT (n 34) Question BT % RP % SPIRIT % P Who attended the SPIRIT education session with the patient? Someone No one No response Urban/GTA or rural address? Urban Rural Are you living in a conjugal relationship? Yes No Highest level of education Elementary Secondary Postsecondary Overall, I am satisfied with the treatment I received Very Somewhat Not at all No response % Would you recommend this treatment to a friend? Yes No Abbreviations: SPIRIT, Surgical Prostatectomy versus Interstitial Radiation Intervention Trial; BT, brachytherapy; RP, radical prostatectomy; GTA, greater Toronto area. at the sessions. Although the primary goal was patient education, the motivation was the trial. We believed that a fully informed patient would be able to appreciate the pros and cons of each modality and thus be more likely to accept random assignment. This commitment to education is time-consuming and impractical on a one-to-one basis but is feasible in a small group setting. The demographics of men consenting to SPIRIT indicate that 85% were urban residents and 79% had postsecondary education, suggesting a potential to benefit from such education measures. One of the major barriers to trial accrual is physicians attitudes toward clinical trials. 17,18 Offering a clinical trial may appear to conflict with individual decision-making and clinical judgment and requires acknowledgment of an uncertainty about the therapeutic benefit or superiority of one treatment over another, 19,20 especially in a trial like SPIRIT where competing modalities are compared. The mutual respect that was fundamental to the multidisciplinary format of our patient education sessions perhaps helped to overcome the professional reluctance to admit uncertainty. Difficult trials that have been successfully completed in the past have changed clinical practice. The National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-06 randomly assigned 2,105 women with breast cancer to total mastectomy or lumpectomy treatment modalities, with or without irradiation. After 12 years of followup, lumpectomy followed by breast irradiation was proven to be appropriate therapy for women in this cohort, thereby sparing countless women a total mastectomy. 21 Another difficult trial was the prospective, multicenter North American Asymptomatic Carotid Artery Stenosis (ACAS) Study in which 1,659 patients with carotid artery stenosis were randomly assigned to either endarterectomy or medical therapy. The relative risk reduction of 53% in the surgical arm changed the standard of care. 22 These trials illustrate major challenges in accrual with comparison of options that from a patient s perspective are very dissimilar. Successful completion has profoundly affected the standard of practice. The urologists and radiation oncologists involved in SPIRIT put aside their biases and professional rivalries to address fundamental questions concerning radical prostatectomy and brachytherapy. Despite their commitment, it became clear after only a few weeks of presenting this trial in a standard fashion to eligible patients that a different approach was necessary. This education intervention was the result. It began as a free-form education session to inform a small group of men and their family members about early-stage prostate cancer, to compare and contrast surgery and brachytherapy, and to explain the reason for the randomized trial. Over the ensuing weeks, a PowerPoint framework was developed, incorporating responses to frequently asked questions, and to the reasons frequently cited for selecting one modality over the other. We tried to ensure that the session was worthwhile for all attendees, regardless of their final treatment decision. When patients were invited to the education session, they were encouraged to bring a relative or friend. This tactic encourages further discussion and is key to assimilating and understanding information. 11,23 Patient feedback was very positive; a tribute to the specialists efforts to maintain a neutral tone. Attendees should feel that they are being informed of their treatment options, that randomization is one option, but that there is no pressure to enter the trial JOURNAL OF CLINICAL ONCOLOGY

4 Toronto Experience With SPIRIT The medical literature reveals clinical equipoise between radical prostatectomy and brachytherapy, but establishing that balance for the individual patient is vital to the success of trials such as SPIRIT. This balance was evident in the joint multidisciplinary presentation; the presence of the urologist and radiation oncologist together spoke volumes to the attendees. Even men who came to the session with their minds made up about their treatment decisions, often went home to reconsider. The interactive nature of the session worked in favor of the trialasmenwoulddiscussamongthemselvesthereasonsfortheirchoices. We acknowledge the differences in health care systems between countries, and in individual settings. The education intervention should be tailored to the needs of the community and the institution. Practice in a multidisciplinary environment may lend itself more readily to the establishment of a multidisciplinary session. Time spent in the small group setting expedites the subsequent consultation, allowing the specialist to focus on matters specific to that particular patient. SPIRIT did not meet accrual expectations and was closed by the American College of Surgeons Oncology Group in April 2004, having randomly assigned only 56 patients in a 2-year period, 15 patients from American centers and 41 from Canada. The disparity between the successful accrual with the education session and that seen elsewhere led to many discussions on the implementation of this approach elsewhere. The PowerPoint presentation was shared with interested centers. Internet access to a video-taped session was also considered. One American and one other Canadian center instituted a similar session and achieved improved accrual with six consents each. Admittedly, a randomized trial comparing radical prostatectomy and brachytherapy is an ambitious undertaking. The lesson learned is that difficult clinical trials may need a different approach. Evidencebased medicine demands evidence-based answers, and so do patients. The Toronto experience with SPIRIT suggests that men who are fully informed and understand their treatment options as presented jointly in an unbiased manner by representative specialists from competing modalities are better equipped to make an informed decision. And in our experience, for one man in six, that informed decision was consent to random assignment. REFERENCES 1. Davis JW, Kuban DA, Lynch DF, et al: Quality of life after treatment for localized prostate cancer: Differences based on treatment modality. J Urol 166: , Stone NN, Stock RG: Practical considerations in permanent brachytherapy for localized adenocarcinoma of the prostate. Urol Clin North Am 30: , Bacon CG, Giovannucci E, Testa M, et al: The impact of cancer treatment on quality of life outcomes for patients with localized prostate cancer. J Urol 166: , Lee WR, Hall MC, McQuellan RP, et al: A prospective quality-of-life study in men with clinically localized prostate carcinoma treated with radical prostatectomy, external beam radiotherapy, or interstitial brachytherapy. Int J Radiat Oncol Biol Phys 51: , Wei JT, Dunn RL, Sandler HM, et al: Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer. J Clin Oncol 20: , 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 35: , Jenkins V, Fallowfield L: Reasons for accepting or declining to participate in randomized clinical trials for cancer therapy. Br J Cancer 82: , Chard JA, Lilford RJ: The use of equipoise in clinical trials. Soc Sci Med 47: , Mills N, et al: Perceptions of equipoise are crucial to trial participation: A qualitative study of men in the ProtecT study. Control Clin Trials 24: , Movsas B, Moughan J, Owen J, et al: Who enrolls onto clinical oncology trials? A patterns of care study analysis. Int J Radiat Oncol Biol Phys 57:S214, 2003 (suppl 2) 11. Sanchez S, Salazar G, Tijero M, et al.: Informed consent procedures: Responsibilities of researchers in developing countries. Bioethics 15: , Henzlova MJ, Blackburn GH, Bradley EJ, et al: Patient perception of a long-term clinical trial: Experience using a close-out questionnaire in the Studies of Left Ventricular Dysfunction (SOLVD) Trial SOLVD Close-Out Working Group. Control Clin Trials 15: , Bevan EG, Chee LC, McGhee SM, et al: Patients attitudes to participation in clinical trials. Br J Clin Pharmacol 35: , Llewellyn-Thomas HA, Thiel EC, Sem FW, et al: Presenting clinical trial information: A comparison of methods. Patient Educ Couns 25:97-107, Ellis PM: Attitudes towards and participation in randomised clinical trials in oncology: A review of the literature. Ann Oncol 11: , Catt S, Fallowfield L, Jenkins V, et al: The informational roles and psychological health of members of 10 oncology multidisciplinary teams in the UK. Br J Cancer 93: , Hunter CP, Frelick RW, Feldman AR, et al: Selection factors in clinical trials: Results from the Community Clinical Oncology Program Physician s Patient Log. Cancer Treat Rep 71: , Ellis PM, Butow PN, Tattersall MH, et al: Randomized clinical trials in oncology: Understanding and attitudes predict willingness to participate. J Clin Oncol 19: , Fallowfield L: Can we improve the professional and personal fulfillment of doctors in cancer medicine? Br J Cancer 71: , Benson AB 3rd, Pregler JP, Bean JA, et al: Oncologists reluctance to accrue patients onto clinical trials: An Illinois Cancer Center study. J Clin Oncol 9: , Fisher B: Clinical trials for the evaluation of cancer therapy. Cancer 54: , 1984 (suppl 11) 22. Mast H, Chambless LE, Mohr JP, et al: Indications for endarterectomy in asymptomatic stenoses of the internal or common carotid artery: Results of the North American ACAS Study [in German]. Zentralbl Chir 121: , Gorelick PB, Harris Y, Burnett B, et al: The recruitment triangle: Reasons why African Americans enroll, refuse to enroll, or voluntarily withdraw from a clinical trial: An interim report from the African-American Antiplatelet Stroke Prevention Study (AAASPS). J Natl Med Assoc 90: , 1998 Appendix The Appendix is included in the full-text version of this article, available online at It is not included in the PDF version (via Adobe Reader ). Authors Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest

5 Wallace et al Author Contributions Conception and design: Neil Fleshner, Juanita Crook Administrative support: Joan Basiuk Provision of study materials or patients: Kris Wallace, Neil Fleshner, Michael Jewett, Joan Basiuk, Juanita Crook Collection and assembly of data: Kris Wallace Data analysis and interpretation: Neil Fleshner, Juanita Crook Manuscript writing: Kris Wallace, Juanita Crook Final approval of manuscript: Kris Wallace, Neil Fleshner, Michael Jewett, Joan Basiuk, Juanita Crook 4162 JOURNAL OF CLINICAL ONCOLOGY