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J Altern Complement Med. 2011 May; 17(5): 469–472.
PMCID: PMC3155098
Copyright 2011, Mary Ann Liebert, Inc.
Recruitment of Participants to a Clinical Trial of Botanical Therapy for Benign Prostatic Hyperplasia
Jeannette Y. Lee, PhD,corresponding author1 Harris E. Foster, Jr., MD,2 Kevin T. McVary, MD,3 Sreelatha Meleth, PhD,4 Karen Stavris, MSN,2 Joe Downey, MSc,5 and John W. Kusek, PhD6
1Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR.
2Department of Surgery, Yale University School of Medicine, New Haven, CT.
3Department of Urology, Northwestern University, Fineberg School of Medicine, Chicago, IL.
4Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
5Departments of Biochemistry and Urology, Queens University, Kingston, Ontario, Canada.
6Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
corresponding authorCorresponding author.
Address correspondence to: Jeannette Y. Lee, PhD, Department of Biostatistics, University of Arkansas for Medical Sciences, 4301 West Markham, #781, Little Rock, AR 72205. E-mail:jylee/at/uams.edu
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Abstract
Objectives
The timely recruitment of study participants is a critical component of successful trials. Benign prostatic hyperplasia (BPH), a common nonmalignant urologic condition among older men, is characterized by lower urinary tract symptoms (LUTS). Successful recruitment methods for a trial of medical therapy for BPH, Medical Therapy of Prostate Symptoms (MTOPS), were mass mailing and advertising. The Complementary and Alternative Medicines Trial for Urological Symptoms (CAMUS) was designed to evaluate a botanical therapy, saw palmetto, for the treatment of BPH. The objective of this study was to evaluate recruitment strategies for CAMUS and to contrast the baseline characteristics of CAMUS participants with those recruited to a similar trial using conventional medical therapy.
Design
CAMUS is a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of saw palmetto given at escalating doses over an 18-month period on relief from LUTS.
Subjects
The target enrollment goal was 350 men with LUTS from 11 clinical centers over a 12-month period. The recruitment techniques used and participants contacted, screened, and randomized through each technique were obtained from the clinical centers. Baseline characteristics of the CAMUS participants were compared with participants in the MTOPS trial who met the CAMUS eligibility criteria for LUTS.
Results
The target enrollment goal was achieved in 11 months. The overall monthly recruitment rate per site was 3.7 and ranged from 2.4 to 8.0. The most successful recruitment methods were mass mailing and advertising, which accounted for 39% and 35% of the study participants, respectively. In comparison to MTOPS participants, CAMUS participants were younger, more highly educated, more diverse, and had less severe urinary symptoms.
Conclusions
Successful recruitment methods for CAMUS were similar to those in MTOPS. The use of botanical therapy attracted a less symptomatic and more educated study population.
Benign prostatic hyperplasia (BPH), a common nonmalignant urologic condition among older men, is characterized by lower urinary tract symptoms (LUTS). Treatment of BPH has undergone a significant change during the past decade from surgery to medical therapy. Complementary and alternative medicines are increasing in popularity in the United States,1–3 and are frequently used by patients with BP.2,4 Since recent reports demonstrated that saw palmetto (Serenoa repens (W. Bartram) Small) at a daily dose of 320 mg was not effective in reducing LUTS,5,6 the Complementary and Alternative Medicines for Urological Symptoms (CAMUS) trial was initiated by the National Institutes of Health to determine whether higher doses of this agent would be effective.
The only detailed report on BPH clinical trial enrollment was from the Medical Therapy for Prostatic Symptoms (MTOPS) trial,7 which evaluated medical therapy.8 This article reports recruitment strategies in CAMUS and compares the characteristics of the CAMUS and MTOPS study populations.
Trial design
The design of the CAMUS trial has been previously described.9 Eligible participants were male, ≥45 years of age, had an American Urological Association Symptom Index (AUA-SI)10 ≥8 and ≤24 with a peak urinary flow rate of ≥4 mL/sec and a voided volume of ≥125 mL.
The primary endpoint was change from baseline to 18 months in the AUA-SI. Study participants were randomized to placebo or escalating doses of saw palmetto at 6-month intervals (320, 640, and 960 mg daily).The overall recruitment goal for the trial was 350 men over a 12-month period at 11 clinical centers with identical recruitment targets.
CAMUS participants were compared to the subset of MTOPS participants who met the CAMUS eligibility criteria for AUA-SI (8–24) with respect to baseline characteristics using Fisher's exact test or Pearson's χ2 test for categorical variables and the t test for independent samples for continuous variables at the two-sided 0.05 significance level.
Recruitment strategies
Eight (8) institutions used mass mailing. Sources of names for mass mailing included former participants in two large cancer prevention clinical trials: the Prostate, Lung, Colorectal and Ovarian (PLCO) trial11 and the Selenium and vitamin E Cancer Prevention Trial (SELECT).12 Two (2) institutions sent letters to men who met the age criteria and who had received medical services within their health systems. One (1) institution used a commercial direct mail list.
Mass e-mailing was used by four sites. Most of the e-mail mailings were targeted at university employees and physicians. One (1) institution used a database of individuals from the community who had previously expressed an interest in being considered for research studies.
Nine (9) clinics used both paid and free advertising. While all of these sites advertised in print media, primarily newspaper, several used radio and online ads for recruitment. Posters and flyers throughout the community and university were used by five centers. Six (6) centers reported identifying potential study participants through chart review of medical records of patients who had been previously treated at their urology clinics.
Recruitment began in June 2008 and ended in April 2009, ahead of schedule. The overall monthly recruitment rate was 3.7 per site and ranged from 2.4 to 8.0. The overall response rate to the initial mailing was 3.2% (Table 1). University of Colorado enrolled 83% of their participants from direct mailing, which targeted PLCO and SELECT participants. Kaiser and Yale recruited 100% and 93% of their study participants, respectively, through mailings to age-eligible male users of their health systems. University of Texas–Southwestern recruited 45% of their enrollees through mailings using a commercial list. Overall, 39% of the study participants were informed about the study through mass mailing (Table 1).
Table 1.
Table 1.
Yield from Each Recruitment Method
Electronic mass mailings were done primarily at four sites: University of Colorado, University of Iowa, University of Texas–Southwestern, and Washington University with response rates of 0.4%, 0.3%, 17%, and 10%, respectively. The proportions of participants recruited through e-mail were 17%, 30%, 15%, and 19% for these institutions, respectively. Studywide, 8% of participants learned about the study through e-mail (Table 1).
Advertising through print or radio media attracted 35% of the study participants (Table 1). Cornell, Northwestern, New York University, Queens University, and University of Maryland recruited over half of their study participants through advertisements.
The CAMUS and MTOPS studies differed in entry criteria. MTOPS included men ≥50 years of age. CAMUS expanded the age criteria to include those ≥45 years of age. In comparison to MTOPS participants, CAMUS participants were younger, more highly educated, and more diverse (Table 2). About 13% of the CAMUS participants were African-American, which reflects the proportion of African-Americans in the U.S. population.13 The proportion of participants with a 4-year college degree or technical degree or postcollege education was 66% in CAMUS and 51% in MTOPS. The difference in educational level between the two studies occurred primarily in the non-Hispanic white participants. For most uroflow measurements and the AUA-SI, CAMUS participants had less severe urinary symptoms than MTOPS participants (Table 2).
Table 2.
Table 2.
Comparison of CAMUS and MTOPS Participants with Baseline AUA-SI ≤24: Demographic Characteristics
Discussion
Recruitment strategies that were effective in the MTOPS study,7 advertising and mass mailing, were equally effective in the CAMUS study. Some of these similarities may be attributed to the fact that most (eight) of the CAMUS sites also participated in MTOPS. There are, however, differences in the study populations with respect to educational level, diversity, and severity of urinary symptoms. Educational levels are positively correlated with use of complementary and alternative medicine.1,3,14–17 There may be a greater interest in botanical therapy among those with minimal symptoms.
Conclusions
It is estimated that approximately 15 million men in the United States had LUTS in 2000, a figure that is expected to increase by 43.6% by 202518 with the aging of the population. It is likely that this population will be the target of future clinical trials.
Acknowledgments
CAMUS Study Group: Steering Committee Chair, Massachusetts General Hospital, Michael J. Barry, MD; Data Coordinating Center, University of Alabama at Birmingham, O. Dale Williams, PhD (Director), Sreeletha Meleth, PhD (Associate Director), Lisa R. Allen.
Clinical Sites: New York University—Andrew McCullough, MD (PI), Brianne Goodwin, BSN, RN (Study Coordinator), Laurie Mantor (Study Coordinator), Artrit Butuci (Research Data Associate); Northern California Kaiser Permanente—Andrew L. Avins, MD, MPH (PI), Harley Goldberg, DO (Co-I), Luisa Hamilton (Study Coordinator); Northwestern University Finberg School of Medicine—Kevin T. McVary, MD (PI), Robert Brannigan, MD (Co-I), Brian Helfand, MD, PhD (Consultant), Maria Velez (Study Coordinator), Nancy Schoenecker, RN, CCRC (Clinical Research Coordinator); Queens University—J. Curtis Nickel, MD (PI), Alvaro Morales (Co-I), D. Robert Siemens, MD (Co-I), Joe Downey, MSc, CCRP (Study Coordinator), Janet Clark-Pereira, CCRP (Study Coordinator); University of Colorado Denver—E. David Crawford, MD (PI), Shandra S. Wilson, MD (Co-I), Paul D. Maroni, MD (Co-I), Patricia DeVore, BS (Clinical Research Coordinator), Cliff Jones (Clinical Research Coordinator); University of Iowa—Karl J. Kreder, MD, MBA (PI), Victoria Sharp, MD, MBA (Co-I), Diane Meyerholz, RN, BSN (Study Coordinator), Mary Eno, RN (Study Coordinator); University of Maryland—Michael J. Naslund, MD (PI), Ganine Markowitz-Chrystal, MS, CCRC (Study Coordinator); University of Texas, Southwestern Medical Center—Claus G. Roehrborn, MD (PI), Brad Hornberger, PA-C (Co-I), Allison Beaver, RN (Study Coordinator), Suzie Carter (Data Manager); Washington University School of Medicine—Gerald L. Andriole, MD (PI), Vivien Gardner, RN, BSN (Study Coordinator), Karen Whitmore (Supervisor Patient Services); Weill Cornell Medical College—Steven A. Kaplan, MD (PI), Alexis E. Te, MD (Co-I), Noreen Buckley, NP, CCRC (Study Coordinator), Maritza Rodriquez (Medical Assistant); Yale University School of Medicine—Harris E. Foster, Jr., MD (PI), John W. Colberg, MD (Co-I), Karen Stavris, RN MSN, CCRC (Study Coordinator).
Biostatistics Consultant: University of Arkansas for Medical Sciences, Jeannette Y. Lee, PhD.
Data Safety Monitoring Board: University of Minnesota VA Medical Center, Timothy J. Wilt, MD, MPH (Chair); University of Illinois at Chicago, Harry H.S. Fong, PhD; University of Chicago, Glenn S. Gerber, MD; University of Virginia, Mikel Gray, RN, PhD, CUNP, FAAN; HeteroGeneity LLC, Freddie Ann Hoffman, MD; University of North Carolina, Gary Koch, PhD; University of California at Los Angeles, Mark Litwin, MD, MPH; US Environmental Protection Agency, Warren E. Lux, MD; Harvard Medical School, Michael P. O'Leary, MD, MPH; Alliance for Prevention of Prostate Cancer, Col (Ret.) James E. Williams, Jr.; Hines VA Hospital CSPCC, Domenic Reda, PhD.
Sponsor, supplier of Saw palmetto fruit extract: Rottapharm/Madaus, Joseph J. Veilleux, RPH, MBA.
Sponsors: National Institutes of Health (NIH); National Institute of Diabetes, Digestive & Kidney Diseases, John W. Kusek, PhD; National Center for Complementary and Alternative Medicine, Catherine M. Meyers, MD, Sheila Caldwell, PhD; Office of Dietary Supplements, Joseph M. Betz, PhD, Paul M. Coates, PhD.
MTOPS Database: The MTOPS study was conducted by the MTOPS investigator and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The manuscript was not prepared in collaboration with the MTOPS investigators and does not necessarily reflect the opinions or view of the MTOPS study of the NIDDK.
Support: CAMUS is funded by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases: U01 DK63795, U01 DK63797, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63831, U01 DK63825, U01 DK 63883, U01 DK63778, and U01 DK63788. Support was provided by the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements, NIH. Saw palmetto fruit extract and matching placebo was supplied by Rottapharm/Madaus.
Disclosure Statement
Kevin McVary has received grant support for or served as a consultant or speaker for Lilly/ICOS, Sanofi-Aventis, Allergan, NIDDK, Advanced Health Medical, Watson Pharmaceuticals, Neotract, and Ferring.
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