Michelle S Hamstra1, Victoria L Pemberton2, Nicholas Dagincourt3, Danielle Hollenbeck-Pringle3, Felicia L Trachtenberg3, James F Cnota1, Andrew M Atz4, Elizabeth Cappella5, Sylvia De Nobele6, Josephine Grima7, Martha King8, Rosalind Korsin9, Linda M Lambert10, Meghan K MacNeal11, Larry W Markham12, Gretchen MacCarrick13, Donna M Sylvester14, Patricia Walter15, Mingfen Xu16, Ronald V Lacro8. 1. Heart Institute Administration, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 2. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA. 3. New England Research Institutes, Inc., Watertown, MA, USA. 4. Medical University of South Carolina, Charleston, SC, USA. 5. Ann and Robert H. Lurie Children's Hospital, Chicago, IL, USA. 6. Ghent University Hospital, Ghent, Belgium. 7. The Marfan Foundation, Port Washington, NY, USA. 8. Harvard Medical School, Boston Children's Hospital, Boston, MA, USA. 9. Children's Hospital of New York, New York, NY, USA. 10. Primary Children's Hospital, University of Utah, Salt Lake City, UT, USA. 11. Icahn School of Medicine at Mount Sinai, New York, NY, USA. 12. The Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, USA. 13. Johns Hopkins School of Medicine, Baltimore, MD, USA. 14. Children's Hospital of Philadelphia, Philadelphia, PA, USA. 15. Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 16. Duke University School of Medicine, Durham, NC, USA.
Abstract
BACKGROUND/AIMS: The Pediatric Heart Network Marfan Trial was a randomized trial comparing atenolol versus losartan on aortic root dilation in 608 children and young adults with Marfan syndrome. Barriers to enrollment included a limited pool of eligible participants, restrictive entry criteria, and a diverse age range that required pediatric and adult expertise. Retention was complicated by a 3-year commitment to a complex study and medication regimen. The Network partnered with the Marfan Foundation, bridging the community with the research. The aims of this study are to report protocol and medication adherence and associated predictive factors, and to describe recruitment and retention strategies. METHODS:Recruitment, retention, and adherence to protocol activities related to the primary outcome were measured. Retention was measured by percentage of enrolled participants with 3-year outcome data. Protocol adherence was calculated by completion rates of study visits, ambulatory electrocardiography (Holter monitoring), and quarterly calls. Medication adherence was assessed by the number of tablets or the amount of liquid in bottles returned. Centers were ranked according to adherence (high, medium, and low tertiles). Recruitment, retention, and adherence questionnaires were completed by sites. Descriptive statistics summarized recruitment, retention, and adherence, as well as questionnaire results. Regression modeling assessed predictors of adherence. RESULTS:Completion rates for visits, Holter monitors, and quarterly calls were 99%, 94%, and 96%, respectively. Primary outcome data at 3 years were obtained for 88% of participants. The mean percentage of medication taken was estimated at 89%. Site and age were associated with all measures of adherence. Young adult and African American participants had lower levels of adherence. Higher adherence sites employed more strategies; had more staffing resources, less key staff turnover, and more collaboration with referring providers; utilized the Foundation's resources; and used a greater number of strategies to recruit, retain, and promote protocol and medication adherence. CONCLUSION:Overall adherence was excellent for this trial conducted within a National Institutes of Health-funded clinical trial network. Strategies specifically targeted to young adults and African Americans may have been beneficial. Many strategies employed by higher adherence sites are ones that any site could easily use, such as greeting families at non-study hospital visits, asking for family feedback, providing calendars for tracking schedules, and recommending apps for medication reminders. Additional key learnings include adherence differences by age, race, and site, the value of collaborative learning, and the importance of partnerships with patient advocacy groups. These lessons could shape recruitment, retention, and adherence to improve the quality of future complex trials involving rare conditions.
RCT Entities:
BACKGROUND/AIMS: The Pediatric Heart Network Marfan Trial was a randomized trial comparing atenolol versus losartan on aortic root dilation in 608 children and young adults with Marfan syndrome. Barriers to enrollment included a limited pool of eligible participants, restrictive entry criteria, and a diverse age range that required pediatric and adult expertise. Retention was complicated by a 3-year commitment to a complex study and medication regimen. The Network partnered with the Marfan Foundation, bridging the community with the research. The aims of this study are to report protocol and medication adherence and associated predictive factors, and to describe recruitment and retention strategies. METHODS: Recruitment, retention, and adherence to protocol activities related to the primary outcome were measured. Retention was measured by percentage of enrolled participants with 3-year outcome data. Protocol adherence was calculated by completion rates of study visits, ambulatory electrocardiography (Holter monitoring), and quarterly calls. Medication adherence was assessed by the number of tablets or the amount of liquid in bottles returned. Centers were ranked according to adherence (high, medium, and low tertiles). Recruitment, retention, and adherence questionnaires were completed by sites. Descriptive statistics summarized recruitment, retention, and adherence, as well as questionnaire results. Regression modeling assessed predictors of adherence. RESULTS: Completion rates for visits, Holter monitors, and quarterly calls were 99%, 94%, and 96%, respectively. Primary outcome data at 3 years were obtained for 88% of participants. The mean percentage of medication taken was estimated at 89%. Site and age were associated with all measures of adherence. Young adult and African American participants had lower levels of adherence. Higher adherence sites employed more strategies; had more staffing resources, less key staff turnover, and more collaboration with referring providers; utilized the Foundation's resources; and used a greater number of strategies to recruit, retain, and promote protocol and medication adherence. CONCLUSION: Overall adherence was excellent for this trial conducted within a National Institutes of Health-funded clinical trial network. Strategies specifically targeted to young adults and African Americans may have been beneficial. Many strategies employed by higher adherence sites are ones that any site could easily use, such as greeting families at non-study hospital visits, asking for family feedback, providing calendars for tracking schedules, and recommending apps for medication reminders. Additional key learnings include adherence differences by age, race, and site, the value of collaborative learning, and the importance of partnerships with patient advocacy groups. These lessons could shape recruitment, retention, and adherence to improve the quality of future complex trials involving rare conditions.
Authors: Supriya Shore; P Michael Ho; Anne Lambert-Kerzner; Thomas J Glorioso; Evan P Carey; Fran Cunningham; Lisa Longo; Cynthia Jackevicius; Adam Rose; Mintu P Turakhia Journal: JAMA Date: 2015-04-14 Impact factor: 56.272
Authors: Laura C Hanson; Janet Bull; Kathryn Wessell; Lisa Massie; Rachael E Bennett; Jean S Kutner; Noreen M Aziz; Amy Abernethy Journal: J Pain Symptom Manage Date: 2014-05-23 Impact factor: 3.612
Authors: Nancy A Pike; Victoria Pemberton; Kerstin Allen; Jeffrey P Jacobs; Daphne T Hsu; Alan B Lewis; Nancy Ghanayem; Linda Lambert; Kari Crawford; Teresa Atz; Rosalind Korsin; Mingfen Xu; Chitra Ravishankar; James Cnota; Gail D Pearson Journal: Cardiol Young Date: 2012-07-05 Impact factor: 1.093
Authors: Jennifer S Li; Steven D Colan; Lynn A Sleeper; Jane W Newburger; Victoria L Pemberton; Andrew M Atz; Meryl S Cohen; Fraser Golding; Gloria L Klein; Ronald V Lacro; Elizabeth Radojewski; Marc E Richmond; L Luann Minich Journal: Am Heart J Date: 2011-02 Impact factor: 4.749
Authors: Jennifer P Habashi; Daniel P Judge; Tammy M Holm; Ronald D Cohn; Bart L Loeys; Timothy K Cooper; Loretha Myers; Erin C Klein; Guosheng Liu; Carla Calvi; Megan Podowski; Enid R Neptune; Marc K Halushka; Djahida Bedja; Kathleen Gabrielson; Daniel B Rifkin; Luca Carta; Francesco Ramirez; David L Huso; Harry C Dietz Journal: Science Date: 2006-04-07 Impact factor: 47.728
Authors: Robby Nieuwlaat; Nancy Wilczynski; Tamara Navarro; Nicholas Hobson; Rebecca Jeffery; Arun Keepanasseril; Thomas Agoritsas; Niraj Mistry; Alfonso Iorio; Susan Jack; Bhairavi Sivaramalingam; Emma Iserman; Reem A Mustafa; Dawn Jedraszewski; Chris Cotoi; R Brian Haynes Journal: Cochrane Database Syst Rev Date: 2014-11-20