A systematic review of the quality of trials evaluating biomedical HIV prevention interventions shows that many lack power

HIV Clinical Trials

Volumn 10, Issue 6, 2009, Pages 413-431

  Graham, Susan M ^a,b   Shah, Prakesh S ^b,c   Aesch, Zoë Costa Von ^d   Beyene, Joseph ^b,e   Bayoumi, Ahmed M ^f,g,h  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF TORONTO   (Canada)

^c MOUNT SINAI HOSPITAL   (Canada)

^d MCGILL UNIVERSITY   (Canada)

^e HOSPITAL FOR SICK CHILDREN   (Canada)

^f UNIVERSITY OF TORONTO   (Canada)

^g ST MICHAEL'S HOSPITAL   (Canada)

^h ST MICHAEL'S HOSPITAL   (Canada)

Author keywords

Clinical trial; HIV; Primary prevention; Research methodology; Statistical bias; Systematic review

Indexed keywords

ACICLOVIR; AZITHROMYCIN; CARBOPOL 974P; CARRAGEENAN; CELLULOSE SULFATE; MICROBICIDE; NONOXINOL 9; PLACEBO; RECOMBINANT GLYCOPROTEIN GP 120; SAWY; TENOFOVIR; UNCLASSIFIED DRUG;

BEHAVIOR THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION RISK; MEDICAL ETHICS; MORBIDITY; PRIORITY JOURNAL; PROPHYLAXIS; REVIEW; SELF REPORT; SEXUAL TRANSMISSION; SYSTEMATIC REVIEW;

AIDS VACCINES; ANTI-INFECTIVE AGENTS; CIRCUMCISION, MALE; CONTRACEPTIVE DEVICES, FEMALE; FEMALE; HIV; HIV INFECTIONS; HUMANS; INCIDENCE; MALE; PATIENT COMPLIANCE; PATIENT DROPOUTS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESEARCH DESIGN;

EID: 76749146444     PISSN: 15284336     EISSN: None     Source Type: Journal    
DOI: 10.1310/hct1006-413     Document Type: Review

References (65)

1. UNAIDS/WHO. Report on the Global HIV/AIDS Epidemic 2008. Geneva, Switzerland: UNAIDS; 2008.
2. Underhill K, Montgomery P, Operario D. Abstinence-plus programs for HIV infection prevention in high-income countries. Cochrane Database Syst Rev. 2008;CD007006.
3. Underhill K, Operario D, Montgomery P. Abstinence-only programs for HIV infection prevention in high-income countries. Cochrane Database Syst Rev. 2007;CD005421.
4. Denison JA, O'Reilly KR, Schmid GP, et al. HIV voluntary counseling and testing and behavioral risk reduction in developing countries: a meta-analysis, 1990-2005. AIDS Behav. 2008;12:363-373.
5. Noar SM. Behavioral interventions to reduce HIV-related sexual risk behavior: review and synthesis of meta-analytic evidence. AIDS Behav. 2008;12:335-353.
6. Auvert B, Taljaard D, Lagarde E, et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med. 2005;2:e298.
7. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007;369:643-656.
8. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007;369:657-666.
9. Sangani P, Rutherford G, Wilkinson D. Population-based interventions for reducing sexually transmitted infections, including HIV infection. Cochrane Database Syst Rev. 2004;CD001220.
10. Padian NS, Buve A, Balkus J, et al. Biomedical interventions to prevent HIV infection: evidence, challenges, and way forward. Lancet. 2008;372:585-599.
11. Mills E, Cooper C, Anema A, Guyatt G. Male circumcision for the prevention of heterosexually acquired HIV infection: a meta-analysis of randomized trials involving 11,050 men. HIV Med. 2008;9:332-335.
12. Okwundu CI, Okoromah C. Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high risk individuals (Protocol). Cochrane Database Syst Rev. 2008;CD007189.
13. Wilkinson D, Ramjee G, Tholandi M, Rutherford G. Nonoxynol-9 for preventing vaginal acquisition of HIV infection by women from men. Cochrane Database Syst Rev. 2002;CD003936.
14. Moher D, Schulz KF, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA. 2001;285:1987-1991. (Pubitemid 32366951)
15. Moher D. CONSORT: an evolving tool to help improve the quality of reports of randomized controlled trials. JAMA. 1998;279:1489-1491.
16. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.0. Cochrane Collaboration; 2008. Available at: www.cochrane.org.
17. Cuzick J. A Wilcoxon-type test for trend. Stat Med. 1985;4:87-89.
18. Kamali A, Quigley M, Nakiyingi J, et al. Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial. Lancet. 2003;361:645-652.
19. Karim SA, Coletti A, Richardson B, et al. Safety and effectiveness of vaginal microbicides buffergel and 0.5% PRO 2000/5 gel for the prevention of HIV infection in women: results of the HPTN 035 Trial. Abstract presented at: 16th Conference on Retroviruses and Opportunistic Infections; February 2009; Montreal, Quebec.
20. Van Damme L, Govinden R, Mirembe FM, et al. Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission. N Engl J Med. 2008;359: 463-472.
21. Van Damme L, Ramjee G, Alary M, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet. 2002;360:971-977.
22. Halpern V, Ogunsola F, Obunge O, et al. Effectiveness of cellulose sulfate vaginal gel for the prevention of HIV infection: results of a Phase III trial in Nigeria. PLoS ONE. 2008;3:e3784.
23. Kreiss J, Ngugi E, Holmes K, et al. Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA. 1992;268:477-482.
24. Richardson BA, Lavreys L, Martin HL Jr, et al. Evaluation of a low-dose nonoxynol-9 gel for the prevention of sexually transmitted diseases: a randomized clinical trial. Sex Transm Dis. 2001;28:394-400.
25. Roddy RE, Zekeng L, Ryan KA, et al. A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases. N Engl J Med. 1998;339:504-510.
26. Peterson L, Nanda K, Opoku BK, et al. SAVVY (C31G) gel for prevention of HIV infection in women: a Phase 3, double-blind, randomized, placebo-controlled trial in Ghana. PLoS ONE. 2007;2:e1312.
27. Feldblum PJ, Adeiga A, Bakare R, et al. SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria. PLoS ONE. 2008;3:e1474.
28. Tatoud R. MDP update: MDP301 phase III trial continues but one arm closes. Microbicides Development Programme, February 14, 2008. Available at: http://www.mdp. mrc.ac.uk. Accessed March 29, 2009.
29. Wawer MJ, Sewankambo NK, Serwadda D, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet. 1999;353:525-535.
30. Buchbinder SP, Mehrotra DV, Duerr A, et al. efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008;372:1881-1893.
31. Gray G, Allen MA, Bekker L, et al. Results from the Phambili (HVTN 503) study: A multicenter double-blind placebocontrolled phase IIB test-of-concept study to evaluate the safety and efficacy of the MRKad5 HIV-1 gag/pol/nef vaccine in HIV-1 uninfected South Africans. Abstract presented at: AIDS Vaccine 2008 Conference; October 2008; Cape Town, South Africa.
32. Peterson L, Taylor D, Roddy R, et al. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin Trials. 2007;2:e27.
33. Padian NS, van der Straten A, Ramjee G, et al. Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial. Lancet. 2007;370:251-261.
34. Grosskurth H, Mosha F, Todd J, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet. 1995;346:530-536.
35. Gregson S, Adamson S, Papaya S, et al. Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe. PLoS Med. 2007;4:e102.
36. Kaul R, Kimani J, Nagelkerke NJ, et al. Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial. JAMA. 2004;291:2555-2562.
37. Flynn NM, Forthal DN, Harro CD, et al. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005;191:654-665.
38. Mitka M. Critics bash HIV vaccine trial analysis. JAMA. 2003;289:1491.
39. Ghys PD, Diallo MO, Ettiegne-Traore V, et al. Effect of interventions to control sexually transmitted disease on the incidence of HIV infection in female sex workers. AIDS. 2001;15:1421-1431.
40. Celum C, Wald A, Hughes J, et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371:2109-2119.
41. Skoler-Karpoff S, Ramjee G, Ahmed K, et al. Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebocontrolled trial. Lancet. 2008;372:1977-1987.
42. Altman DG. Statistics in medical journals: some recent trends. Stat Med. 2000;19:3275-3289.
43. Watson-Jones D, Weiss HA, Rusizoka M, et al. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med. 2008;358: 1560-1571.
44. Pitisuttithum P, Gilbert P, Gurwith M, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006;194:1661-1671.
45. Lagakos SW, Gable AR. Challenges to HIV prevention -seeking effective measures in the absence of a vaccine. N Engl J Med. 2008;358:1543-1545.
46. Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001;134:663-694. (Pubitemid 32322245)
47. Laine C, Horton R, DeAngelis CD, et al. Clinical trial registration--looking back and moving ahead. N Engl J Med. 2007;356:2734-2736. (Pubitemid 47001046)
48. Gulmezoglu AM, Pang T, Horton R, Dickersin K. WHO facilitates international collaboration in setting standards for clinical trial registration. Lancet. 2005;365:1829-1831.
49. Bates R, Bertelsen J, Chauvette P, et al. Development of a centralized trials registry for research on HIV/AIDS prevention. Presented at: 6th International Cochrane Colloquium; 1998; Baltimore.
50. Roddy RE, Zekeng L, Ryan KA, et al. Effect of nonoxynol-9 gel on urogenital gonorrhea and chlamydial infection: a randomized controlled trial. JAMA. 2002;287:1117-1122.
51. Mauck CK, Straten A. Using objective markers to assess participant behavior in HIV prevention trials of vaginal microbicides. J Acquir Immune Defic Syndr. 2008;49:64-69.
52. Baeten JM, Richardson BA, Martin HL Jr, et al. Trends in HIV-1 incidence in a cohort of prostitutes in Kenya: implications for HIV-1 vaccine efficacy trials. J Acquir Immune Defic Syndr. 2000;24:458-464.
53. Ramjee G, Kapiga S, Weiss S, et al. The value of site preparedness studies for future implementation of phase 2/ IIb/III HIV prevention trials: experience from the HPTN 055 study. J Acquir Immune Defic Syndr. 2008;47:93-100.
54. Grijsen ML, Graham SM, Mwangome M, et al. Screening for genital and anorectal sexually transmitted infections in HIV prevention trials in Africa. Sex Transm Infect. 2008;84:364-370.
55. de Bruyn G, Martinson N, Nkala B, et al. Male circumcision as a component of the standard for HIV prevention: Experience from a phase IIb vaccine trial in Soweto. Presented at: 15th Conference on Retroviruses and Opportunistic Infections; 2008; Boston.
56. Auvert B, Males S, Puren A, et al. Can highly active antiretroviral therapy reduce the spread of HIV?: A study in a township of South Africa. J Acquir Immune Defic Syndr. 2004;36:613-621.
57. Gray RH, Li X, Wawer MJ, et al. Stochastic simulation of the impact of antiretroviral therapy and HIV vaccines on HIV transmission; Rakai, Uganda. AIDS. 2003;17: 1941-1951.
58. Altman DG, Bland JM. Absence of evidence is not evidence of absence. BMJ. 1995;311:485.
59. Huwiler-Muntener K, Juni P, Junker C, Egger M. Quality of reporting of randomized trials as a measure of methodologic quality. JAMA. 2002;287:2801-2804.
60. Raymond EG, Taylor D, Cates W Jr, et al. Pregnancy in effectiveness trials of HIV prevention agents. Sex Transm Dis. 2007;34:1035-1039.
61. Hayes R, Mosha F, Nicoll A, et al. A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 1. Design. AIDS. 1995;9:919-926.
62. Wawer MJ, Gray RH, Sewankambo NK, et al. A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda. AIDS. 1998;12:1211-1225.
63. Kamali A, Kinsman J, Nalweyiso N, et al. A community randomized controlled trial to investigate impact of improved STD management and behavioural interventions on HIV incidence in rural Masaka, Uganda: trial design, methods and baseline fi ndings. Trop Med Int Health. 2002;7:1053-1063.
64. Fonck K, Kaul R, Kimani J, et al. A randomized, placebocontrolled trial of monthly azithromycin prophylaxis to prevent sexually transmitted infections and HIV-1 in Kenyan sex workers: study design and baseline fi ndings. Int J STD AIDS. 2000;11:804-811.
65. Harro CD, Judson FN, Gorse GJ, et al. Recruitment and baseline epidemiologic profile of participants in the first phase 3 HIV vaccine efficacy trial. J Acquir Immune Defic Syndr. 2004;37:1385-1392.