Using DHS to Identify Sites for HIV Prevention Trials

Recruiting high-risk, HIV-negative participants is challenging for HIV prevention trials. This study aimed to 1) identify and characterize subsets of high-risk women based on responses to demographic and psychosocial questions from the AIDS Indicator Survey (AIS) and 2) develop a rapid, inexpensive tool for site identification. We developed a latent class model (LCM), hypothesizing that AIS respondents could be grouped by responses to psychosocial indicators, and that these latent classes would vary by HIV status, socio-demographic, and other indicators. We tested our model on women respondents from the Tanzania 2003 AIS Survey, and replicated it in several other populations.  LCM produced four classes of women who significantly varied by psychosocial indicators and HIV status. Geographic differences in HIV prevalence and class composition were observed. Our approach has the potential to provide a more systematic, inexpensive and rapid strategy to identify HIV prevention trial sites

Using preliminary data and prospective power analyses for mid-stream revision of projected group and subgroup sizes in pragmatic patient-centered outcomes research

Pragmatic clinical trials are commonly used in patient-centered outcomes research to assess heterogeneity of treatment effects. Patient-Centered Outcomes Research Institute (PCORI) methodology standards for assessing heterogeneity of treatment effects are extremely rigorous, but their implementation in real-world settings can be difficult. Predicting recruitment effectiveness and subgroup characteristics is often challenging and may require mid-stream revision of projected group and subgroup sizes. Yet, little real-world data are available to demonstrate methodologically valid approaches to address situations where such revisions are necessary. These data were used for mid-stream revision of group and subgroup sizes in the Management of Diabetes in Everyday Life (MODEL) clinical trial. The planned number of randomized participants retained over the one-year study period was reduced from 800 to 581 due to recruitment difficulties among potential participants residing in rural areas. Prospective power analyses are based on the revised target of 581 participants retained and the proportions of 167 participants with various key baseline characteristics, who had been randomized in MODEL by January 2018, as reported to the Patient Center Outcomes Research Institute (PCORI) and the MODEL Data Safety and Monitoring Committee. Power calculations are based on two-sided t-tests with type-I error rates of 0.05 and the assumption that effect sizes will range from small (standardized difference = 0.36) to medium (= 0.50). The primary outcome variables are how many days in the previous week participants 1) ate healthy meals, 2) participated in at least 30 minutes of physical activity, and 3) took medications as prescribed. The POWER procedure of SAS 9.4 was used for all analyses. These data, along with the approach, can assist statisticians as they plan future pragmatic clinical trials evaluating heterogeneity of treatment effects. These data can help inform investigators, conducting patient-centered outcomes research, as they define subgroups for either confirmatory analyses for testing heterogeneity of treatment effects or for exploratory analyses where estimation of confidence bounds may be useful for generating future hypotheses. (This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (SC15-1503-28336), www.ClinicalTrials.gov and Identifier: NCT02957513 [1].

Predicting Product Adherence in a Topical Microbicide Safety Trial in Pune, India

The inconclusive results of past trials and recent findings of partial protection of Tenofovir 1% gel underscore the need to better understand product adherence in microbicide trials. This study aimed to identify factors predicting couples’ ability to sustain topical gel and condom use during clinical trial participation. We enrolled 100 Indian participants of a randomized, controlled safety trial of Tenofovir 1% gel (CT cohort) and 100 similar women who were ineligible or declined trial participation (NCT cohort). Compared to the NCT cohort, CT women reported higher baseline condom use, more positive attitudes towards condoms and higher levels of protection efficacy. While NCT condom use remained low, CT condom use increased dramatically during the study. Reported gel consistency was higher than condom consistency. Individual and couple-related factors predicted condom consistency and interest in future gel use, but not gel consistency. Findings could inform trial recruitment strategies and product introduction

Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model

ObjectiveWe tested the hypothesis that rapamycin coated onto, and eluted from, expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal hyperplasia in a porcine model.MethodsRapamycin (also called sirolimus) was coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE grafts by using an adhesive polymer that allows timed release of the drug. An adhesive polymer that allows timed release of rapamycin from ePTFE was developed with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft integrity was characterized by scanning electron microscopy, and rapamycin levels were quantified by using high-performance liquid chromatography. Twenty-two mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive-only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End-to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal-diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to-side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12 mm long. All animals received aspirin (325 mg orally) daily. All animals were given oral aspirin (325 mg) daily beginning on the day before surgery. At 28 days, the animals were killed, and the grafts were explanted in continuity with the adjacent aortic cuff and the outflow iliac artery. Variables compared between groups included graft patency, distal anastomotic length and cross-sectional narrowing, and intimal thickness at the arterial-graft junction indexed to the adjacent graft thickness. Microscopic analysis was performed with hematoxylin and eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to experimental groups graded sections for collagen deposition, neointima formation, inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration.ResultsAll animals survived until they were killed without clinical evidence of limb ischemia or graft infection. Preplanned t tests in the context of one-way analysis of variance showed no difference in outcome measures between the untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were combined in further comparisons with the adhesive- and rapamycin-coated ePTFE group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P < .0001) and less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P = .0007) when compared with the other two groups by using two-tailed Student t tests. There was no evidence of medial necrosis or aneurysmal degeneration. All patent grafts had complete endothelialization on hematoxylin and eosin sections. Rapamycin was detectable and quantifiable in the arterial wall at 28 days after implantation.ConclusionsRapamycin can be coated onto and eluted from ePTFE by using a nonionic polymer and a simple coating technique. At 4 weeks after implantation, the rapamycin-eluting ePTFE grafts demonstrate gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with non–drug-eluting ePTFE. Four weeks after implantation in a porcine model, rapamycin-eluting ePTFE grafts demonstrated gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with untreated and adhesive-only coated ePTFE grafts.Clinical RelevanceRapamycin-eluting ePTFE grafts decrease neointimal hyperplasia in a porcine model. Further studies are needed to evaluate whether patency will be improved. Rapamycin-eluting ePTFE grafts may allow the use of prosthetic grafts in situations in which autologous vein is unavailable and in which neointimal hyperplasia is pronounced, such as in small-diameter (<6-mm) vessels typical of infrapopliteal interventions

Women and ARVâ based prevention: opportunities and challenges

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138349/1/jia29419.pd

Content validity of the EORTC quality of life questionnaire QLQ-C30 for use in cancer

Aim The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) is among the most widely used patient-reported outcome measures in cancer research and practice. It was developed prior to guidance that content should be established directly from patients to confirm it measures concepts of interest and is appropriate and comprehensive for the intended population. This study evaluated the content validity of the QLQ-C30 for use with cancer patients. Methods Adults undergoing cancer treatment in Europe and the USA participated in open-ended concept elicitation interviews regarding their functional health, symptoms, side-effects and impacts on health-related quality of life. Thematic analysis was conducted, and similarities across cancer types, disease stages and countries or languages were explored. Results Interviews with 113 patients with cancer (85 European, 28 USA) including breast, lung, prostate, colorectal and other cancers were conducted between 2016 and 2020. Conceptual saturation was achieved. The most frequently reported concepts were included in the QLQ-C30 conceptual framework. QLQ-C30 items were widely understood across language versions and were relevant to patients across cancer types and disease stages. While several new concepts were elicited such as difficulty climbing steps or stairs, weight loss, skin problems and numbness, many were not widely experienced and/or could be considered sub-concepts of existing concepts. Conclusions The QLQ-C30 demonstrates good evidence of content validity for the assessment of functional health, symptom burden and health-related quality of life in patients with localised-to-advanced cancer

Acceptability of an open-label wait-listed trial design: Experiences from the PROUD PrEP study

Background PROUD participants were randomly assigned to receive pre-exposure prophylaxis (PrEP) immediately or after a deferred period of one-year. We report on the acceptability of this open-label wait-listed trial design. Methods Participants completed an acceptability questionnaire, which included categorical study acceptability data and free-text data on most and least liked aspects of the study. We also conducted in-depth interviews (IDI) with a purposely selected sub-sample of participants. Results Acceptability questionnaires were completed by 76% (415/544) of participants. After controlling for age, immediate-group participants were almost twice as likely as deferred-group participants to complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the majority of participants in both groups found the wait-listed design acceptable when measured by satisfaction of joining the study, intention to remain in the study, and interest in joining a subsequent study. However, three-quarters thought that the chance of being in the deferred-group might put other volunteers off joining the study. In free-text responses, data collection tools were the most frequently reported least liked aspect of the study. A fifth of deferred participants reported ‘being deferred’ as the thing they least liked about the study. However, more deferred participants disliked the data collection tools than the fact that they had to wait a year to access PrEP. Participants in the IDIs had a good understanding of the rationale for the open-label wait-listed study design. Most accepted the design but acknowledged they were, or would have been, disappointed to be randomised to the deferred group. Five of the 25 participants interviewed reported some objection to the wait-listed design. Conclusion The quantitative and qualitative findings suggest that in an environment where PrEP was not available, the rationale for the wait-listed trial design was well understood and generally acceptable to most participants in this study