Collier 2005.
| Methods | Patients (n = 282) were randomized upon entry to receive either each study site's usual adherence support measures (n = 140) or each study site's usual adherence support measures and scripted serial telephone calls from study site staff members (n = 142). Exact method of allocation concealment was not described | |
| Participants | Patients had < or = to 200 CD4+ T cells/mm3 or >80,000 HIV RNA copies/ml of plasma at screening, no or limited previous antiretroviral therapy (no previous use of lamivudine, nonnucleoside reverse transcriptase inhibitors, or protease inhibitors), hemoglobin > or = to 9.1 g/dl (for men) or > or = to 8.9 g/dl (for women), > or = to 850 neutrophils/mm3, > 65,000 platelets/mm3, hepatic aminotransferase levels < 5 times the upper limit of reference values, and amylase levels < 1.5 times the upper limit of reference values, and could not be pregnant or breast‐feeding | |
| Interventions | The intervention group received serial, supportive telephone calls. Study site staff members (mostly nurses) followed a standardized script for telephone calls and received training by the study team. Spanish and Italian translations of the English script were provided. The telephone calls focused on each subject's medication‐taking behavior, and study site staff members identified barriers to adherence and developed individualized strategies to increase adherence. During the telephone calls, the study site staff members also provided social support and assistance with the management of side effects. The telephone calls were to be made at specific times: 1 to 3 days after the initiation of the study regimen and at weeks 1, 2, 3, 6, 12, and every 8 weeks thereafter, as long as the subject continued to receive the assigned study regimen, for a maximum of 16 telephone calls over the course of 96 weeks. For each telephone call, a minimum of 2 attempts were made to contact the patient before leaving a counseling or general message. Also, a complete telephone call was one where all the topics described above were discussed, however, if that did not occur, calls were categorized as being only partially completed. The usual adherence support measures included an average of 35 minutes of in‐person counseling provided by a study site nurse or pharmacist at the start of treatment. According to a study site survey, 67% of study sites reported providing written materials to study subjects as part of their usual adherence support measures. As well, 41% reported making at least 1 telephone call to selected subjects (deemed at being high risk for low adherence) as part of their usual support measures; however, the telephone calls were made to a minority of patients, the number of calls per patient was limited, and the content was not standardized | |
| Outcomes | Compliance was measured at baseline using a standardized adherence questionnaire and a follow‐up questionnaire evaluating medication‐taking behavior during the preceding 4 days at weeks 8, 16, 24, 48, 72, and 96 The primary health outcome was a measure of antiretroviral drug activity, specifically, the time to virologic failure. Virologic failure was defined as (1) having > than or = to 200 HIV RNA copies/ml of plasma at or after week 24 or (2) having an increase of > 1.0 log10 above nadir levels or an increase to or above baseline levels before week 24 or (3) having 2 consecutive HIV RNA levels > than or = to 200 copies/ml at any time after having 2 consecutive HIV RNA levels < 200 copies/ml |
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| Notes | ― | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Random number generation was not described. (pg 1399) "Subjects in the substudy were randomized at entry to receive either each study site's usual adherence support measures (usual support measures group) or each study site's usual adherence support measures and scripted serial telephone calls from study site staff members (calls group)." |
| Allocation concealment (selection bias) | Unclear risk | No mention of allocation concealment ‐ (pg 1399) "Subjects in the substudy were randomized at entry to receive either each study site's usual adherence support measures (usual support measures group) or each study site's usual adherence support measures and scripted serial telephone calls from study site staff members (calls group). Study site staff members (mostly nurses) followed a standardized script for telephone calls and received training by the study team by conference call before the study started." |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | Unclear risk | Some limitations were noted by the authors but insufficient information to make a judgment |
| Blinding of outcome assessment (detection bias) Adherence measure | High risk | (PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Adherence assessors (not explicitly stated) were apparently not blinded. The original trial, of which this is a substudy was open‐labeled. The phone calls were made by nurses; no statement regarding their blinding. (pg 1399) "Study site staff members (mostly nurses) followed a standardized script for telephone calls and received training by the study team by conference call before the study started." |
| Blinding of outcome assessment (detection bias) Patient outcome | Low risk | (PRIMARY) VIRAL LOAD ‐ Objective outcome |
| Blinding of participants (performance bias) Adherence measure | High risk | (PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ No blinding done in this study, subjective outcome. (pg 1399) "open‐label study" |
| Blinding of participants (performance bias) Patient outcome | Low risk | (PRIMARY) VIRAL LOAD ‐ Objective outcome |
| Blinding of personnel (performance bias) Adherence measure | Unclear risk | (PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ No blinding done in this study; not clear how study personnel might influence outcome ‐ (pg 1399) "open‐label study" |
| Blinding of personnel (performance bias) Patient outcome | Low risk | (PRIMARY) VIRAL LOAD ‐ Objective outcome |
| Incomplete outcome data (attrition bias) Adherence measure | Unclear risk | (PRIMARY) SELF REPORT ‐ QUESTIONNAIRE ‐ Groups for dropouts not clear. Of the 282 enrollees, 239 (85%) completed ACTG 746, 35 (12%) prematurely discontinued ACTG 388 (and, thus, ACTG 746), 6 (2%) died, and 2 discontinued for other reasons. The categories were similar between the groups but insufficient information to make a judgment |
| Incomplete outcome data (attrition bias) Patient outcome | Unclear risk | (PRIMARY) VIRAL LOAD ‐ Unclear whether the missing data would have changed the results |