Journal of Clinical Epidemiology
Volume 52, Issue 12 , Pages 1143-1156 , December 1999

Barriers to Participation in Randomised Controlled Trials: A Systematic Review

  • Sue Ross

      Affiliations

    • Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom
    • Corresponding Author InformationAddress for correspondence: Dr. Sue Ross, Health Services Research Unit, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD; UK
    • ,
  • Adrian Grant

      Affiliations

    • Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom
    • ,
  • Carl Counsell

      Affiliations

    • Cochrane Stroke Review Group, Western General Hospital, Edinburgh, United Kingdom
    • ,
  • William Gillespie

      Affiliations

    • Department of Orthopaedic Surgery, University of Edinburgh, Edinburgh, United Kingdom
    • ,
  • Ian Russell

      Affiliations

    • Department of Health Sciences and Clinical Evaluation, University of York, York, United Kingdom
    • ,
  • Robin Prescott

      Affiliations

    • Medical Statistics Unit, University of Edinburgh, Edinburgh, United Kingdom

,Accepted 28 June 1999.

References 

  1. Swanson GM, Ward AJ. Recruiting minorities into clinical trials (Toward a participant-friendly system). J Natl Cancer Inst. 1995;87:1747–1759
  2. Hunninghake DB, Darby CA, Probstfield JL. Recruitment experience in clinical trials (literature summary and annotated bibliography). Control Clin Trials. 1987;8(4 Suppl):6S–30S
  3. Charlson ME, Horwitz RI. Applying results of randomised trials to clinical practice (impact of losses before randomisation). BMJ. 1984;289:1281–1284
  4. Easterbrook PJ, Matthews DR. Fate of research studies. J R Soc Med. 1992;85:71–76
  5. Ashery RS, McAuliffe WE. Implementation issues and techniques in randomized trials of outpatient psychosocial treatments for drug abusers (recruitment of subjects). Am J Drug Alcohol Abuse. 1992;18:305–329
  6. Holden G, Rosenberg G, Barker K, Tuhrim S, Brenner B. The recruitment of research participants (a review). Social Work in Health Care. 1993;19:1–44
  7. Aaronson NK, VisserPol E, Leenhouts GHMW, Muller MJ, Van der Schot ACM, Van Dam FSAM, et al  Telephone-based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials. J Clin Oncol. 1996;14:984–996
  8. Dickinson CJ. Clinical research in the NHS today. J R Coll Physicians Lond. 1994;28:460–463
  9. Foley JF, Moertel CG. Improving accrual into cancer clinical trials. J Cancer Educ. 1991;6:165–173
  10. Smyth JF, Mossman J, Hall R, Hepburn S, Pinkerton R, Richards M, et al. Conducting clinical research in the new NHS (The model of cancer. United Kingdom Coordinating Committee on Cancer Research). BMJ. 1994;309:457–461
  11. Benson AB, Pregler JP, Bean JA, Rademaker AW, Eshler B, Anderson K. Oncologists' reluctance to accrue patient onto clinical trials (An Illinois Cancer Center Study). J Clin Oncol. 1991;9:2067–2075
  12. Fisher WB, Cohen SJ, Hammond MK, Turner S, Loehrer PJ. Clinical trials in cancer therapy (Efforts to improve patient enrollment by community oncologists). Med Pediatr Oncol. 1991;19:165–168
  13. Schaeffer MH, Krantz DS, Wichman A, Masur H, Reed E, Vinicky JK. The impact of disease severity on the informed consent process in clinical research. Am J Med. 1996;100:261–268
  14. Taylor KM. The doctor's dilemma (Physician participation in randomized clinical trials). Cancer Treat Rep. 1985;69:1095–1100
  15. Taylor KM, Margolese RG, Soskolne CL. Physicians' reasons for not entering eligible patients in a randomized clinical trial of surgery for breast cancer. N Engl J Med. 1984;310:1363–1367
  16. Taylor KM, Kelner M. Interpreting physician participation in randomized clinical trials (The physician orientation profile). J Health Soc Behav. 1987;28:389–400
  17. Taylor KM. Physician participation in a randomized clinical trial for ocular melanoma. Ann Opthalmol. 1992;24:337–344
  18. Taylor KM, Feldstein ML, Skeel RT, Pandya KJ, Ng P, Carbone PP. Fundamental dilemmas of the randomized clinical trial process (Results of a survey of the 1,737 Eastern Cooperative Oncology Group investigators). J Clin Oncol. 1994;12:1796–1805
  19. Tognoni G, Alli C, Avanzini F, Bettelli G, Colombo F, Corso R, et al. Randomised clinical trials in general practice (Lessons from a failure). BMJ. 1991;303:969–971
  20. Winn RJ, Miransky J, Kerner JK, Kennelly L, Michaelson RA, Sturgeon SR. An evaluation of physician determinants in the referral of patients for cancer clinical trials in the community setting. Prog Clin Biol Res. 1984;156:63–73
  21. Wadland WC, Hughes JR, Seckler Walker RG, Bronson DL, Fenwick J. Recruitment in a primary care trial on smoking cessation. Fam Med. 1990;22:201–204
  22. Shea S, Bigger JT, Campion J, Fleiss JL, Rolnitzky LM, Schron E, et al. Enrollment in clinical trials (Institutional factors affecting enrollment in the cardiac arrhythmia suppression trial (CAST)). Control Clin Trials. 1992;13:466–486
  23. Morse EV, Simon PM, Besch CL, Walker J. Issues of recruitment, retention, and compliance in community-based clinical trials with traditionally underserved populations. Appl Nurs Res. 1995;8:8–14
  24. Penn ZJ, Steer PJ. Reasons for declining participation in a prospective randomized trial to determine the optimum mode of delivery of the preterm breech. Control Clin Trials. 1990;11:226–231
  25. Henzlova MJ, Blackburn BH, Bradley EJ, Rogers WJ. Patient perception of a long-term clinical trial (Experience using a close-out questionnaire in the Studies of Left Ventricular dysfunction (SOLVD) trial). Control Clin Trials. 1994;15:284–293
  26. Taylor KM, Shapiro M, Soskolne CL, Margolese RG. Physician response to informed consent regulations for randomized clinical trials. Cancer. 1987;60:1415–1422
  27. Taylor KM. Integrating conflicting professional roles (Physician participation in randomized clinical trials). Soc Sci Med. 1992;35:217–224
  28. Siminoff LA, Fetting JH, Abeloff MD. Doctor-patient communication about breast cancer adjuvant therapy. J Clin Oncol. 1989;7:1192–1200
  29. Langley GR, Sutherland HJ, Wong S, Minkin S, Llewellyn-Thomas HA, Till JE. Why are (or are not) patients given the option to enter clinical trials?. Control Clin Trials. 1987;8:49–59
  30. Chang RW, Falconer J, Stullberg SD, Arnold WJ, Dyer AR. Prerandomization (An alternative to classic randomization. The effects on recruitment in a controlled trial of arthroscopy for osteoarthrosis of the knee). J Bone Joint Surg Am. 1990;72:1451–1455
  31. Simes RJ, Tattersall MH, Coates AS, Raghavan D, Solomon HJ, Smartt H. Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer. BMJ. 1986;293:1065–1068
  32. Antman K, Amato D, Wood W, Carson J, Suit H, Proppe K, et al. Selection bias in clinical trials. J Clin Oncol. 1985;3:1142–1147
  33. Plaiser PW, Berger MY, van der Hull RL, Nijs HG, den Toom R, Terpstra OT, et al. Unexpected difficulties in randomizing patients in a surgical trial (A prospective study comparing extracorporeal shock wave lithotripsy with open cholecystectomy). World J Surg. 1994;18:769–772
  34. Williams CJ, Zwitter M. Informed consent in European Multicentre randomised clinical trials—Are patients really informed?. Eur J Cancer. 1994;30A:907–910
  35. Gallo C, Perrone F, De Placido S, Guisti C. Informed versus randomised consent to clinical trials. Lancet. 1995;346:1060–1064
  36. Autret E, Dutertre JP, Barbier P, Jonville AP, Pierre F, Berger C. Parental opinions about biomedical research in children in Tours, France. Developmental Pharmacology and Therapeutics. 1993;20:64–71
  37. Harth SC, Thong YH. Sociodemographic and motivational characteristics of parents who volunteer their children for clinical research (A controlled study). BMJ. 1990;300:1372–1375
  38. Cunny KA, Miller HW. Participation in clinical drug studies (Motivations and barriers). Clin Ther. 1994;16:273–282
  39. Bowen J, Hirsch S. Recruitment rates and factors affecting recruitment for a clinical trial of a putative anti-psychotic agent in the treatment of acute schizophrenia. Human Psychopharmacology. 1992;7:337–341
  40. Hunter CP, Frelick RW, Feldman AR, Bavier AR, Dunlap WH, Ford L, et al  Selection factors in clinical trials (Results form the Community Clinical Oncology Program Physician's Patient Log). Cancer Treat Rep. 1987;71:559–565
  41. Simel DL, Feussner JR. A randomized controlled trial comparing quantitative informed consent formats. J Clin Epidemiol. 1991;44:771–777
  42. Moody LE, Gregory SJ, Bocanegra T, Vasey F. Search and research (Factors influencing post-menopausal African-American women's participation in a clinical trial). J Am Acad Nurse Pract. 1995;7:483–488
  43. Schwartz CE, Fox BH. Who say yes? Identifying selection biases in a psychosocial intervention study of multiple sclerosis. Soc Sci Med. 1995;40:359–370
  44. Atwood JR, Haase J, Rees-McGee S, Blackwell G, Giordano L, Earnest D, et al  Reasons related to adherence in community-based field studies. Patient Education & Counselling. 1992;19:251–259
  45. Wingerson D, Sullivan M, Dager S, Flick S, Dunner D, Roy-Byrne P. Personality traits and early discontinuation from clinical trials in anxious patients. Journal of Clinical Psychopharmacology. 1993;13:194–197
  46. Sutherland HJ, Carlin K, Harper W, Martin LJ, Greenberg CV, Till JE, et al. A study of diet and breast cancer prevention in Canada (Why healthy women participate in controlled trials). Cancer Causes Control. 1993;4:521–528
  47. Morrison W. Trial and tribulations (patients' perspectives of the BETASERON study). AXON. 1994;16:51–54
  48. Yeomans Kinney A, Vernon SW, Frankowski RF, Weber DM, Bitsura JM, Vogel VG. Factors related to enrolment in the breast cancer prevention trial at a comprehensive cancer center during the first year of recruitment. Cancer. 1995;76:46–56
  49. Orr PR, Blackhurst DW, Hawkins BS. Patient and clinical factors predictive of missed visits and inactive status in a multicenter clinical trial. The Macular Photocoagulation Study Group. Control Clin Trials. 1992;13:40–49
  50. DeLuca SA, Korcuska LA, Oberstar BH, Rosenthal ML, Welsh PA, Topol EJ. Are we promoting true informed consent in cardiovascular clinical trials?. J Cardiovasc Nurs. 1995;9:54–61
  51. Jensen AB, Madsen B, Andersen P, Rose C. Information for cancer patients entering a clinical trial—An evaluation of an information strategy. Eur J Cancer. 1993;29A:2235–2238
  52. Larson E, McGuire DB. Patient experiences with research in a tertiary care setting. Nurs Res. 1990;39:168–171
  53. Lynoe N, Sandlund M, Dahlqvist G, Jacobsson L. Informed consent (Study of quality of information given to participants in a clinical trial). BMJ. 1991;303:610–613
  54. Newburg SM, Holland AE, Pearce LA. Motivation of subjects to participate in a research trial. Appl Nurs Res. 1992;5:89–93
  55. Ross MW, Jeffords K, Gold J. Reasons for entry into an understanding of HIV/AIDS clinical trials (A preliminary study). AIDS Care. 1993;6:77–82
  56. Slevin M, Mossman J, Bowling A, Leonard R, Steward W, Harper P, et al. Volunteers or victims (Patients' views of randomised cancer clinical trials). Br J Cancer. 1995;71:1270–1274
  57. Harth SC, Thong YH. Parental perceptions and attitudes about informed consent in clinical research involving children. Soc Sci Med. 1995;40:1573–1577
  58. Bevan EG, Chee LC, McInnes GT. Patients' attitudes to participation in clinical trials. Br J Clin Pharmacol. 1992;34:156P–157P
  59. Bergmann JF, Chassany O, Gandiol J, Deblois P, Kanis JA, Segrestaa JM, et al. A randomized clinical trial of the effect of informed consent on the analgesic activity of placebo and naproxen in cancer pain. Clinical Trials and Meta-Analysis. 1994;29:41–47
  60. Dahan R, Caulin C, Figea L, Kanis JA, Caulin F, Segrestaa JM. Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital. BMJ Clin Res. 1986;293:363–364
  61. Jack WJ, Chetty U, Rodger A. Recruitment to a prospective breast conservation trial (Why are so few patients randomised?). BMJ. 1990;301:83–85
  62. Tindall B, Forde S, Ross MW, Goldstein D, Barker S, Cooper DA. Effects of two formats of informed consent on knowledge amongst persons with advanced HIV disease in a clinical trial of didanosine. Patient Education & Counselling. 1994;24:261–266
  63. Stone JM, Page FJ, Laidlaw CR, Cooper I. Selection of patients for randomised trials (A study based on the MACOP-B vs CHOP in NHL study). Aust N Z J Med. 1994;24:536–540
  64. Llewellyn-Thomas HA, McGreal MJ, Thiel EC, Fine S, Erlichman C. Patients' willingness to enter clinical trials (Measuring the association with perceived benefit and preference for decision participation). Soc Sci Med. 1991;32:35–42
  65. Roberson NL. Clinical trial participation. Viewpoints from racial/ethnic groups. Cancer. 1994;74(9 Suppl):2687–2691
  66. Robinson SB, Ashley M, Haynes MA. Attitudes of African-Americans regarding prostate cancer clinical trials. J Community Health. 1996;21:77–87
  67. Corbett F, Oldham J, Lilford R. Offering patients entry in clinical trials (Preliminary study of the views of prospective participants). J Med Ethics. 1996;22:227–231
  68. Maslin A. A survey of the opinions on “informed consent” of women currently involved in clinical trials within a breast unit. Eur J Cancer Care (Eng Lang Ed). 1994;3:153–162
  69. Myers MG, Cairns JA, Singer J. The consent form as a possible cause of side effects. Clin Pharmacol Ther. 1987;42:250–253
  70. Llewellyn-Thomas HA, Thiel EC, Sem FWC, Woermke DEH. Presenting clinical trial information (A comparison of methods). Patient Education & Counseling. 1995;25:97–107
  71. Llewellyn-Thomas HA, McGreal MJ, Thiel EC. Cancer patients' decision making and trial-entry preferences (the effects of “framing” information about short-term toxicity and long-term survival). Med Decis Making. 1995;15:4–12
  72. Fetting JH, Siminoff LA, Piantadosi S, Abeloff MD, Damron DJ, Sarsfield AM. Effect of patients' expectations of benefit with standard breast cancer adjuvant chemotherapy on participation in a randomized clinical trial (A clinical vignette study). J Clin Oncol. 1990;8:1476–1482
  73. Olver IN, Buchanan L, Laidlaw C, Poulton G. The adequacy of consent forms for informing patients entering oncological clinical trials. Ann Oncol. 1995;6:867–870
  74. Simel DL, Feussner JR. Suspended judgement. Clinical trials of informed consent. Control Clin Trials. 1992;13:321–324
  75. Dunbar J, Cleary PA, Siebert C, Baker L, Brink S, Nathan DM. Implementation of a multicomponent process to obtain informed consent in the diabetes control and complications trial. Control Clin Trials. 1989;10:83–96
  76. Tankanow RM, Sweet BV, Weisopf JA. Patients' perceived understanding of informed consent in investigational drug studies. Am J Hosp Pharm. 1992;49:633–635
  77. Miller C, Searight HR, Grable D, Schwartz R, Sowell C, Barbarash RA. Comprehension and recall of the informational content of the informed consent document (An evaluation of 168 patients in a controlled clinical trial). J Clin Research and Drug Development. 1994;8:237–248
  78. Wilcox M, Schroer S. The perspective of patients with vascular disease on participation in clinical trials. J Vasc Nurs. 1994;12:112–116
  79. Deber RB, Thompson GG. Variations in breast cancer treatment decisions and their impact in mounting trials. Control Clin Trials. 1990;11:353–373
  80. Klein MC, Kaczorowski J, Robbins JM, Gautheir RJ, Jorgensen SH, Joshi AK. Physicians' beliefs and behaviour during a randomized controlled trial of episotomy (consequences for women in their care). Can Med Assoc. 1995;153:769–779
  81. Coombs DW, Dimick A, Bronstein JM, Potts LH, Bowens B. Conceptual and methodologic problems in the evaluation of a new burn treatment modality. J Burn Care Rehabil. 1993;14:568–571
  82. Bowen JT, Barnes TRE. The clinical characteristics of schizophrenic patients consenting or not consenting to a placebo controlled trial of antipsychotic medication. Human Psychopharmacology. 1994;9:423–433
  83. Lerman C, Rimer BK, Daly M, Lustbader E, Sands C, Balshem A, et al. Recruiting high risk women into a breast cancer health promotion trial. Cancer Epidemiol Biomarkers Prev. 1994;3:271–276
  84. Nystrom KM, Froman WB, Holdsworth MT. Clinical research trials (Evaluation of a recruitment strategy for healthy elders). J Clin Res Pharmacoepidemiology. 1992;6:293–301
  85. Chalmers I, Altman DG. Systematic Reviews. London, UK: BMJ Publications, 1995.
  86. Lovato LC, Hill K, Hertert S, Hunninghake DB, Probstfield JL. Recruitment for controlled clinical trials (Literature summary and annotated bibliography). Control Clin Trials. 1997;18:328–357

PII: S0895-4356(99)00141-9

Journal of Clinical Epidemiology
Volume 52, Issue 12 , Pages 1143-1156 , December 1999

Article Tools