Differences in Baseline Characteristics and Outcomes at 1- and 2-Year Follow-up of Cancer Survivors Accrued via Self-Referral versus Cancer Registry in the FRESH START Diet and Exercise Trial

Recruitment to research trials is challenging (1, 2). Fewer than 5% of cancer patients participate in clinical trials (3). Institutional constraints and privacy issues contribute to the costly and labor-intensive process of subject recruitment (2). Furthermore, cancer registry policies regarding patient education and physician involvement deter researchers’ ability to notify patients about research opportunities (1, 4). These barriers affect recruitment strategies, design, and cost (2).

Researchers may diversify recruitment strategies to expand the subject pool for clinical trials (5). Although recruitment through advertisement has been commonly used for clinical trials targeting diseases, such as diabetes and hypertension, which affect 20% to 30% of American adults (6, 7), to date, such means have not been frequently pursued in oncology trials primarily due to low cancer prevalence (3-4%) (8). However, the Internet now makes it possible to reach cancer survivors (newly diagnosed and long-term) for clinical trials. The differences between survivors responding to these solicitations, compared with those recruited from cancer registries, however, are not known. No studies have reported differences in characteristics or outcomes in behavioral interventions among self-referred versus registry-ascertained cancer study subjects, although such differences have been documented in other health conditions (5, 9, 10). For example, differences in motivation have been observed among people who self-referred to a weight management program versus those ascertained from clinics (11). Furthermore, self-referred problem drinkers were more likely to reduce alcohol consumption with bibliotherapy (self-help) than those identified through at-risk screening (12). Advertisement may yield cost savings by reducing recruitment duration (5); however, such strategies might yield biased samples whose characteristics and study performance are not generalizable to populations of interest (9, 10).

We compared cancer survivors accrued from two sources, self-referral and cancer registry, enrolled in a two-arm randomized behavioral lifestyle intervention trial entitled FRESH START, testing the efficacy and durability of sequentially tailored versus standardized print materials in improving diet and exercise behaviors of breast and prostate cancer survivors (13, 14). We hypothesized that, compared with participants ascertained from cancer registries, those who self-referred might differ with regard to cancer coping style (that is, manifest higher proportions of “fighting spirits” versus “fatalists”) and also have higher levels of interest, readiness, and self-efficacy to pursue lifestyle change at baseline. In addition, we speculated that self-referred participants would show greater levels of adherence once enrolled in the intervention.

The methods and main outcomes for this trial have been reported elsewhere (13, 14). Briefly, potential study participants who were within 9 months of diagnosis with early-stage female breast or prostate cancer (in situ, localized, or regional) were identified using two accrual sources: (a) cases rapidly ascertained through cancer registries with subsequent approval from their oncology care physicians and (b) self-referrals responding to study flyers, magazine articles, Internet sites, targeted list-serves (e.g., NexCura©, Inc.), support groups, national meetings, and word of mouth. Institutional review boards at all participating institutions approved the study, which complied with the Health Insurance Portability and Accountability Act guidelines.

From July 2002 to August 2004, a total of 762 survivors responded with interest (42% response rate), provided written consent, and were screened to exclude individuals with medical or physical conditions precluding unsupervised exercise or a high fruit and vegetable diet (13, 14). Individuals also were excluded if they practiced at least two of the following behaviors: (a) consumption of five or more daily servings of fruits and vegetables, (b) adherence to a diet <30% of energy from fat, and/or (c) participation in >150 min of exercise weekly. After screening, 543 participants were enrolled.

Participants completed two computer-assisted telephone interviews of 45 to 55 min each at baseline and at 1- and 2-year follow-up. Minutes per week of moderate, hard, and very hard exercise of at least five metabolic equivalents (MET-kcal/kg/h) were captured using the 7-day Physical Activity Recall (15). Servings per day of fruits and vegetables and percent energy from fat (total and saturated) were derived using the Diet History Questionnaire (16). Additionally, at baseline, the following additional measures were collected: sociodemographic characteristics (treatment, education, and income); cancer coping style (modified Mini-Mental Adjustment to Cancer subscale); barriers to exercise and eating a low-fat, high fruit and vegetable diet; quality-of-life (Functional Assessment of Cancer Therapy); risk for depression (Center for Epidemiologic Studies of Depression); social support (Duke Social Support Index); comorbidity; perceived health; self-efficacy and stage of readiness for exercising ≥150 min/wk, eating five or more servings of fruits and vegetables per day and consuming a low-fat diet; smoking; and weight status (12).

The interventions are described in detail elsewhere (13, 17, 18). Briefly, participants in both groups received a personalized workbook and additional information to improve diet and exercise behaviors. The intervention arm received sequentially tailored mailed materials over a 10-month period sent as a series of seven newsletters every 6 weeks for each behavior being addressed. The attention control arm received standardized print materials in the public domain on diet and exercise (13). Both groups also received a brief survey between each mailing.

Self-referred participants were compared with registry participants on variables measured at baseline, 1 year, and 2 years. The 1- and 2-year outcomes included lifestyle practices, adherence, and attrition rates. Differences between self-referred and registry participants on baseline measures, adherence, and attrition rates were tested using t tests or the χ² tests, as appropriate. Comparison of the tailored intervention and attention control study arms by self-referral versus registry patients on 1- and 2-year outcome data were tested in separate regression models, one model for each outcome variable and each time point. Logistic regression was used to test for accrual group differences in attainment of each of the three goal behaviors (yes/no); ordinal logistic regression was used to test for a group difference in number of goal behaviors achieved; and the general linear model was used to test for group differences on each of the continuous outcome variables. The following baseline variables were controlled for in all models: study arm, the outcome under study, percent energy from dietary fat, number of servings of fruits and vegetables, exercise minutes, the number of behaviors already practicing at baseline (0 or 1), gender, race, and social support. All analyses were done using SAS (version 9.1, 2003; SAS Institute).

A total of 543 individuals were accrued, including 209 self-referred and 334 registry ascertained. Self-referred subjects were more likely than registry subjects to respond with interest (80% versus 33%, respectively; P = 0.001; Fig. 1). When compared with registry participants, self-referred participants were significantly younger, more likely to have received chemotherapy (owing to more aggressive disease among women with breast cancer), more likely to identify with the “fighting spirit” cancer coping style, more likely to report greater self-efficacy for fat restriction, a greater stage of readiness to exercise and restrict fat, lower quality-of-life, fewer comorbid conditions, and lesser frequency of eating five or more daily fruits and vegetables (Table 1).

There were no significant associations between accrual source and study arm, adherence, adverse health events, or attrition (dropouts) at either follow-up time point. Means (SD) for adherence for self-referred versus registry participants were 5.6 (2.3) and 5.5 (2.3), respectively. Approximately 52% of self-referred participants compared with 55% of registry participants reported at least one health event. Ninety-five percent of participants (regardless of accrual source) completed 1 year of the study, whereas by 2 years the rate declined to 89% and 91% for self-referred and registry participants, respectively.

Table 2 presents change scores for frequencies and means (SE) from baseline to 1-year follow-up by study arm and accrual source for the 519 subjects who completed the 1-year assessment. Comparing self-referred and registry participants in the intervention arm, there were no significant differences in weekly exercise minutes, percent energy from fat, fruit and vegetable daily servings, or number of behaviors practiced at goal levels (data not shown) at 1-year follow-up. Within the control arm, self-referred participants showed significantly greater increases in exercise and fruit and vegetable consumption after 1-year follow-up (P values <0.05) and also experienced significantly more durable effects with regard to fruit and vegetable consumption after 2-year follow-up when compared with registry participants (+1.25 versus +0.38 daily servings, respectively; P = 0.007) Self-referred participants in the control arm also significantly increased the numbers of behaviors practiced at goal levels at 1-year follow-up compared with registry participants (0 goal achievement = −15.9% versus −3.6%; 1 goal achievement = −10.8% versus −9.1%; 2 goal achievement = 20.8% versus 12.1%; and 3 goal achievement = 5.9% versus 0.6%, respectively; P = 0.01).

To our knowledge, this is the first trial comparing the characteristics and performance of self-referred versus registry-ascertained cancer survivors in a lifestyle intervention trial. Our findings have implications for the utility of diverse recruitment strategies in expanding the available population for cancer research studies.

Self-referral sources may be particularly useful to bolster both response rate and accrual for home-based behavioral intervention studies and may offer a cost-effective approach to recruitment. By adding self-referral sources to the standard registry-ascertained cases, we reduced the time required for sample accrual and also achieved some measure of cost savings. However, self-referral sources also introduced bias, because these participants were younger and reported lower quality-of-life and fewer comorbid conditions. Despite these differences, we were surprised to find no observed differences between accrual groups with regard to income, education, and minority status. This was a similar finding to Henrikson et al., who reported that participants who self-referred to a genetics registry were comparable in terms of demographic characteristics (except education) to an actively recruited population-based sample, whereas psychosocial differences existed between the groups (10). FRESH START, however, like many diet and exercise interventions that target cancer survivors, accrued a mostly White (83%) and upper socioeconomic sample (19). Our ability to observe a differential in socioeconomic diversity may have been limited.

Our findings also are similar to those of Scholle et al., who enrolled bipolar disorder registry members via diverse recruitment sources that included health professionals, the Internet, support groups, and general marketing (5). Their data suggest that the cost per participant accrued was substantially lower for registrants accrued via support groups and Internet sources than those ascertained via health professionals and general marketing. Unlike our study, these investigators found that both strategies yielded a more highly educated sample; however, like our study, participants accrued via the Internet were significantly younger than registrants from all other groups. Further, in a study of irritable bowel syndrome subjects, Lee et al. found that the type of recruitment method used (advertisement versus clinic referral) affected patient characteristics, including demographics, physical and psychologic symptoms, and quality-of-life (9).

Perhaps the most important finding of this secondary analysis was that whereas self-referred and registry participants performed similarly in the tailored intervention arm, self-referred participants performed significantly better than registry participants in the attention control arm (receiving standardized materials) in terms of exercise and fruit and vegetable consumption. One could intuit that individuals who actively seek enrollment into a behavioral intervention trial might be more motivated than those who are solicited from a cancer registry. Binks and O'Neil also found greater levels of motivation for weight loss among individuals who self-referred compared with individuals who were physician-referred to a weight loss program (11). However, these findings differ from FRESH START in that they found no differences in weight loss by accrual source. Indeed, our study may be similar to a meta-analysis by Apodaca and Miller, who found that self-help bibliotherapy was less effective among drinkers who were identified through at risk screening than those who were self-referred (12). Whereas self-referred populations may benefit from standardized health promotion materials that are low in cost, populations that do not actively seek health promotion opportunities (that is, cases solicited from registries and clinics) may require tailored interventions to achieve behavior change.

In conclusion, researchers must continue to devise efficient, low-cost, high-yield recruitment strategies to achieve targeted accrual. At the same time, researchers must work toward broader dissemination of lifestyle interventions to the growing population of cancer survivors. Efforts must be made to recruit representative populations and craft interventions that enable behavior modification. Although it was less costly and more efficient to enroll participants who self-referred to FRESH START, researchers should consider potential differences in characteristics and outcomes at the time of recruitment planning and study implementation.

No potential conflicts of interest were disclosed.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The authors dedicate this article in memory of our esteemed and beloved colleague, Dr. Elizabeth C. Clipp. We thank Drs. Marci Campbell, Harvey Cohen, Bethany Jackson, P. Kelly Marcom, Bess Marcus, and Thomas Polascik for their guidance in areas of design and implementation; Drs. Walter Ettinger, Frank Harrell, and Thomas Scott for serving on our external data safety and monitoring board; the contributions and professionalism demonstrated by the staff of People Designs, Inc. (David Farrell, MPH; Jetze Beers; Marley Beers, MFA; and Kristin Trangsrud, MPH) who helped craft the FRESH START intervention materials, and Dr. Cecelia and Len Doak of Patient Learning Associates, Inc., who helped make them easily understandable. We also thank the following individuals who have and are continuing to contribute expertise and support: Sreenivas Algoti, MS; Teresa Baker; Rita Freeman; Sonya Goode Green, MPH; Heather MacDonald; Paige Miller; Barbara Parker; Shelley Rusincovitch; Rachel Schanberg, MS; Valeda Stull; and Russell Ward. We also are grateful to our participating institutions (Duke University Medical Center, Durham Regional Hospital, Durham VA Medical Center, Maria Parham Hospital, New Hanover Regional Medical Center, Raleigh Community Hospital, Rex Healthcare, and The University of Chicago), cancer registrars/patient care coordinators (Gloria Adams, Renee Gooch, Blanche Sellars, Dortch Smith, Donna Thompson and Cheri Willard), and participating physicians (Drs. Victor E. Abraham, Anjana Acharya, David Albala, Alex Althausen, Everett Anderson, Roger F. Anderson, Mitchell Anscher, Guillermo Arana, Carlos Arcangelli, Sucha Asbell, Ann Aspera, Michael Aspera, James N. Atkins, Cheryl Aylesworth, Margaret Barnes, Brian Bauer, Louis Baumann, Michael Beall, Gregory Bebb, Michael Beecher, John Bell, Marc Benevides, Brian C. Bennett, Robert Bennett, Robert Bennion, James Benton, Stuart Bergman, William R. Berry, Kelly Blair, Kimberly Blackwell, Gayle Blouin, Peter Blumencranz, William Bobbitt III, Daniel Borison, William Bouchelle, Elaine Bouttell, Don Boychuk, Barb Boyer, Albert Brady, Thomas Brammer, Scott Brantley, Joanna Brell, Charles Brendler, Thomas Brennan, Donald Brennan, Elizabeth Brew, Thomas Bright, Philip Brodak, Dieter Bruno, Dale Bryansmith, Niall Buckley, Walter W. Burns, W. Woodrow Burns, Thomas Buroker, Barbara Burtness, Amanullah Buzdar, David Caldwell, Elizabeth E. Campbell, Susan Campos, Sean Canale, Woodward Cannon, Dominick Carbone, Albert Casazza, George Case, Michael Cashdollar, Stanton Champion, Nitin Chandramouli, Marie Chenn, S. Chew, Stephen Chia, Warren Chin, Richard Chiulli, Elaine Chottiner, Walter Chow, Peter Clark, Kenneth Collins, Barry Conway, Suzanne Conzen, David Cook, John Corman, Shawn Cotton, D. Scott Covington, Edwin B. Cox, Jeffrey Crane, Frank Critz, Nancy J. Crowley, Sam Currin, Brian Czernieki, Brian Czito, Bruce Dalkin, John T. Daniel, John Danneberger, Leroy Darkes, Glenn Davis, Michael Davis, Walter E. Davis, Jean de Kernion, Pat DeFusco, Fletcher Derrick, Margaret Deutsch, Gayle Dilalla, Robert Diloreto, Craig Donatucci, Michael Donovan, John Doster, Bradford Drury, Paul Dudrick, William Dunlap, Edward Eigner, Maha Elkordy, Matthew Ellis, Richard Evans, Jerry Fain, Anne Favret, Ira Fenton, Dirk Fisher, James Foster, Wyatt Fowler, Jeffrey Freeland, Daniel Frenning, Ralf Freter, Michael Frontiera, Michele Gadd, Anthony Galanos, Ronald Garcia, Antonio Gargurevich, Helen Garson, Richard Gavigan, Morris Geffen, Gregory Georgiade, Ward Gillett, Paul Gilman, Jeffrey Gingrich, Deborah Glassman, John Gockerman, Richard Goodjoin, J. Phillip Goodson, Joel Goodwin, Teong Gooi, Jeffrey Gordon, Narender Gorukanit, James Gottesman, Lav Goyal, William Graber, Margaret Gradison, Gordon Grado, Mark Graham, Michael Grant, Stephen Greco, Carl Greene, Peter Grimm, Nima Grissom, Irina Gurevich, Carol Hahn, Alex Haick, Craig Hall, Edward Halperin, Sabah Hamad, R. Erik Hartvigsen, Harold Harvey, Paul Hatcher, James Hathorn, Robert Hathorn, Carolyn Hendricks, David Hesse, Martin Hightower, Peter Ho, Leroy Hoffman, Frankie Ann Holmes, Sidney Hopkins, Samuel Huang, Robert Huben, Cliff Hudis, Thelma Hurd, Sally Ingram, Philip Israel, Naresh Jain, Nora Jaskowiak, Jean Joseph, Jacqueline Joyce, Walton Joyner, Ray Joyner, Scott Kahn, Sachin Kamath, Carsten Kampe, Michael Kane, Richard Kane, Michael Kasper, Uday Kavde, Thomas Keeler, Douglas Kelly, Michael Kent, Kevin Kerlin, Kenneth Kern, Huathin Khaw, Jay Kim, Houston Kimbrough, Charmaine Kim-Sing, John Kishell, Petras Kisielius, Arthur Klose, George Kmetz, Lawrence Knott, Ronald Konchanin, Cyrus Kotwall, Kenneth Kotz, Charles Kraus, Bruce Kressel, Alan Kritz, John Lacey, Susan Laing, David Larson, John Lasater, Barry Lee, W. Robert Lee, Douglas Leet, Natasha Leighl, George Leight, Paul LeMarbre, Herbert Lepor, Seth Lerner, Margaret Levy, Lori Lilley, Steve Limentani, Robert Lineberger, Lenis Livesay, Walter Loehr, Fred J. Long, Richard Love, Mark Lucas, James Lugg, Charles Lusch, H. Kim Lyerly, Janet Macheledt, Thomas Maddox, Patrick Maguire, Mark Makhuli, Rajeev Malik, Mary Manascalco-Theberge, P. Kelly Marcom, Manfred Marcus, Neal Mariados, Lawrence Marks, Shona Martin, Eric Matayoshi, Gordon Mathes, Mark McClure, Scott McGinnis, David McLeod, Warren McMurry, William McNulty, Robert McWilliams, Cynthia Menard, Mani Menon, Richard Michaelson, Michael Mikolajczyk, David Miles, Dixie Mills, Jesse Mills, David Mintzer, David Molthorp, Allen Mondzac, Gustavo Montana, Angelica Montesano, Leslie Montgomery, Joseph O. Moore, William Morgan, Patricia Morrison, Michael A. Morse, Jacek Mostwin, Judd Moul, Ziyad Mugharbil, Brian Murphy, William Muuse, J. William Myers, Richard S. Myers, Richard Mynatt, Gene Naftulin, Vishwanath Nagale, Niam Nazha, Charles Neal, James Neidhart, Joseph D. Neighbors, Philip Newhall, Robert Nichols, William Niedrach, Peter Oh, John Oh, John A. Olson, Robert Ornitz, David Ornstein, Alexander Panutich, Maria Papaspyrou, Steven Papish, Dhaval Parikh, James Parsons, George Paschal, Robert Paterson, Dev Paul, David F. Paulson, Samuel Peretsman, Jorge Perez, Mark Perman, Thomas Phillips, Thomas Polascik, Klaus Porzig, David C. Powell, Kenneth Prebil, Glenn Preminger, Adele Preto, Leonard Prosnitz, Robert Prosnitz, Scott K. Pruitt, Michael Pryor, Milton Quigless, Robert Reagan, Carl Reese, C.F. Reid, John Reilly, Robert Renner, Alan Rice, Melvin Richter, John Rickabaugh, Adrien Rivard, Ralph Roan, Cary Robertson, Steve Robeson, Linda Robinson, Mark Romer, Eric Rosen, Amy Rosenthal, Alison Ross, William Russell, Lewis Russell, Charles Scarantino, Candace Schiffer, Mark Schoenberg, Mark Scholz, William Schuessler, Stuart Schwartzberg, Janell Seeger, Victoria Seewaldt, Hillard Seigler, Pearl Seo, Phillip Shadduck, Timothy Shafman, Rohit Shah, Arieh Shalhav, Peter Shapiro, Fred Shapiro, Heather Shaw, Robert Siegel, Daniel Silver, Mary Simmonds, Jane Skelton, Barbara Smith, Mitchell Sokoloff, Douglas Sorensen, Angela Soto-Hamlin, Alexander Sparkuhl, Thomas Spears, Merle Sprague, Mark St. Lezin, Steven J. Stafford, B. Dino Stea, Gary Steinberg, Patricia Steinecker, Mary Stewart, Jerry Stirman, Lewis Stocks, Scott Stoioff, Christopher Stokoe, Warren Streisand, Mark Sturdivant, Paul Sugar, Steven Sukh, Steven Sukin, Perry Sutaria, Linda Sutton, Phillip Sutton, John Sylvester, Beth Szuck, Darrell Tackett, Ernesto Tan, Sharon Taylor, John Taylor, Dina Tebcherany, Chris Teigland, Marcos Tepper, Haluk Tezcan, William Thoms, Ellis Tinsley, Jr., Lisa Tolnitch, Angel Torano, Frank Tortora, William Truscott, Theodore Tsangaris, Peter Tucker, Walter Tucker, Ingolf Tuerk, Wade Turlington, Richard Tushman, Michael Tyner, Pascal Udekwu, Eric Uhlman, Henry Unger, Linda Vahdat, Louis Vandermolen, George Vassar, Margaret Vereb, Johannes Vieweg, Daniel Vig, Tom Vo, Walter Vogel, David Wahl, B. Alan Wallstedt, Patrick Walsh, Philip Walther, Robert Waterhouse, Charles Wehbie, Seth Weinreb, Marissa Weiss, Raul Weiss, Geoffrey White, Edward Whitesides, Lee Wilke, Hamilton Williams, Matthew Wilner, Don Wilson, James S. Wilson, Bristol Winslow, Rachel Wissner, James Wolf, Lawrence Womack, Charles Woodhouse, Clifford Yaffe, Daniel Yao, Richard Yelverton, Lemuel Yerby, Mark Yoffe, Martin York, Gregory Zagaja, Kenneth Zeitler, Elizabeth Zubek, and Raul Zunzunegui). Most of all, we are indebted to the many cancer survivors who helped us pilot test, retest, and then formally test the intervention.