Application of a composite measure of product adherence, protocol compliance, and semen exposure to a phase III microbicide HIV prevention trial

Abstract Background Strict adherence to antiretroviral-based microbicide use is important for effective HIV prevention. We previously developed a composite measure of product adherence, protocol compliance, and semen exposure for determining vaginal use of tenofovir (TFV) 1% gel applicators through biomarkers and residual drug analyses. In this study, we tested the ability of the composite measure in vaginally used TFV gel applicators from a Phase III HIV prevention clinical trial. Methods Used vaginal gel applicators from the FACTS 001 study were swabbed for detection of vaginal bacterial markers (vaginal insertion), semen DNA markers (semen exposure), and residual TFV gel (product use). Results Of 1,098 evaluable TFV and placebo applicators, 80% had detectable vaginal insertion biomarkers and 52% had semen biomarkers. Ninety-nine percent of vaginally inserted applicators TFV applicators had detectable residual TFV as measured by liquid chromatography with tandem mass spectroscopy (LC–MS/MS). Residual TFV levels were also successfully detected using Fourier Transform Infrared (FTIR)-based spectroscopy. Conclusions Vaginal insertion and semen exposure biomarkers were detectable on used TFV 1% gel applicators. Residual TFV on these gel applicators was detectable by LC–MS/MS and FTIR-based spectroscopy, which has potential to be a more convenient and quicker method for detecting drug use. With continual improvements, this composite measure of product adherence, protocol compliance, and semen exposure has potential to assess use of not only TFV gel but also other topical microbicides or products.

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Development of a Composite Measure of Product Adherence, Protocol Compliance, and Semen Exposure Using DNA and Protein Biomarkers for Topical HIV Prevention Studies

PLoS ONE ◽

10.1371/journal.pone.0114368 ◽

2014 ◽

Vol 9 (12) ◽

pp. e114368 ◽

Cited By ~ 2

Author(s):

Terry A. Jacot ◽

Ashley Nelson ◽

Andrea Thurman ◽

Angela D. M. Kashuba ◽

David F. Archer ◽

...

Keyword(s):

Hiv Prevention ◽

Composite Measure ◽

Protein Biomarkers ◽

Prevention Studies ◽

Protocol Compliance

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Adherence Improvement Innovations to Enhance Protocol Compliance and Vaginal Ring Adherence in a Phase III HIV Prevention Study in KwaZulu-Natal

AIDS Research and Human Retroviruses ◽

10.1089/aid.2014.5339.abstract ◽

2014 ◽

Vol 30 (S1) ◽

pp. A163-A163

Author(s):

Chantel Friend ◽

Philip Kotze ◽

Annalene Nel

Keyword(s):

Hiv Prevention ◽

Vaginal Ring ◽

Phase Iii ◽

Prevention Study ◽

Kwazulu Natal ◽

Protocol Compliance

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Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00286-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Fabio Puglisi ◽

Lorenzo Gerratana ◽

Matteo Lambertini ◽

Marcello Ceppi ◽

Luca Boni ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Effect ◽

Hormone Receptor ◽

Recurrence Risk ◽

Receptor Expression ◽

Phase Iii ◽

Composite Measure ◽

Node Positive ◽

Hormone Receptor Positive ◽

Dose Dense

AbstractThe GIM2 phase III trial demonstrated the benefit of dose-dense chemotherapy in node-positive early breast cancer (eBC). To better define the dose-dense effect in the hormone receptor-positive subgroup, we evaluated its benefit through a composite measure of recurrence risk. We conducted an ancillary analysis of the GIM2 trial evaluating the absolute treatment effect through a composite measure of recurrence risk (CPRS) in patients with hormone receptor-positive HER2-negative eBC. CPRS was estimated through Cox proportional hazards models applied to the different clinicopathological features. The treatment effect was compared to the values of CPRS by using the Sub-population Treatment Effect Pattern Plot (STEPP) process. The Disease-Free Survival (DFS)-oriented STEPP analysis showed distinct patterns of relative treatment effect with respect to CPRS. Overall, 5-year DFS differed across CPRS quartiles ranging from 95.2 to 66.4%. Each CPRS quartile was characterized by a different patients’ composition, especially for age, lymph node involvement, tumor size, estrogen and progesterone receptor expression, and Ki-67. A number needed to treat of 154 and 6 was associated with the lowest and the highest CPRS quartile, respectively. Dose-dense adjuvant chemotherapy showed a consistent benefit in node-positive eBC patients with hormone receptor-positive HER2-negative disease, but its effect varied according to CPRS.

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Critical Impact of Radiotherapy Protocol Compliance and Quality in the Treatment of Advanced Head and Neck Cancer: Results From TROG 02.02

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.4498 ◽

2010 ◽

Vol 28 (18) ◽

pp. 2996-3001 ◽

Cited By ~ 457

Author(s):

Lester J. Peters ◽

Brian O'Sullivan ◽

Jordi Giralt ◽

Thomas J. Fitzgerald ◽

Andy Trotti ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Phase Iii ◽

Treatment Center ◽

Tumor Control ◽

Advanced Head ◽

Number Of Patients ◽

Protocol Compliance ◽

The Impact

Purpose To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer. Patients and Methods The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality. Results At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; ≥ 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): −2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively. Conclusion These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.

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