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Le Touquet – Paris-Plage, France

Grossman C.I.,U.S. National Institutes of Health | Ross A.L.,ANRS | Auerbach J.D.,University of California at San Francisco | Ananworanich J.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc | And 6 more authors.
Trends in Microbiology | Year: 2016

The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multidisciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV-cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community. © 2015.

Borand L.,Institute Pasteur in Cambodia | Laureillard D.,ANRS | Madec Y.,Institute Pasteur Paris | Chou M.,University of Health Sciences | And 7 more authors.
Antiviral Therapy | Year: 2013

Background: The optimal dose of efavirenz for HIV-infected patients receiving a tuberculosis regimen including rifampicin remains debated, especially for subjects weighing over 50 kg. To address this issue, we measured plasma efavirenz concentrations from Cambodian adults with tuberculosis enrolled in the CAMELIA randomized trial (ClinicalTrials.gov number, NCT01300481) 6 weeks after the onset of antiretroviral therapy. Methods: Efavirenz concentrations and proportions of patients with concentrations below 1,000 ng/ml were compared across patient body weight below or above 50 kg using a Student's t-test and a χ2 test, respectively. Factors associated with efavirenz concentrations below 1,000 ng/ml were identified by logistic regression analysis. Logistic regression analysis was also performed to check if efavirenz concentrations below 1,000 ng/ml were associated with virological failure. Results: Plasma efavirenz concentrations were higher in the 332 patients who weighed <50 kg compared with the 150 who weighed ≥50 kg (median [IQR] 2,859 [1,787-4,749] and 2,060 [1,425-3,575] ng/ml, respectively; P=0.02). However, the proportion of patients with efavirenz concentrations below 1,000 ng/ml was not different between those weighing less than or more than 50 kg (6% and 10%, respectively; P=0.13) and a body weight above 50 kg was not associated with a higher risk of plasma efavirenz concentrations below 1,000 ng/ml. When plasma efavirenz concentrations below 1,000 ng/ml were present, they were not associated with virological failure. Conclusions: The current WHO guidelines recommending 600 mg efavirenz daily irrespective of patient's body weight remains a safe and effective approach to treating coinfected adults needing simultaneous tuberculosis and HIV therapy. ©2013 International Medical Press.

Journot V.,French Institute of Health and Medical Research | Perusat-Villetorte S.,French Institute of Health and Medical Research | Bouyssou C.,French Institute of Health and Medical Research | Couffin-Cadiergues S.,ANRS | And 4 more authors.
Clinical Trials | Year: 2013

Background In biomedical research, the consent form must comply with regulatory requirements. Checking for compliance typically has been performed on-site and most frequently after a participants final enrollment. We use a procedure for remote preenrollment checking of consent forms that protects participant identities. This procedure requires a copy of the consent form that partially masks the fields for participants name and signature; this copy is faxed to the clinical trials unit for checking. Purpose To describe our efforts to identify an appropriate printed masking pattern. We tried several patterns that permit ascertainment of the presence of signatures and names and evaluated each one with respect to degree of masking participant identities. Methods We assessed the efficiency of a satisfactory pattern through an experiment. We created forms with variants of the masking pattern on the copy to be faxed. We completed the forms with fictitious identities before copies were faxed and checked by clinical research associates. We measured the rate of empty and filled fields detected and the rate of letters and names correctly read. The target was defined as 100% for the rate of empty and filled fields detected and 0% for the rate of letters and names correctly read. Results The best masking pattern allowed the detection of 100% empty and filled fields and the reading of 0% names and 19% letters. Consequently, the consent form with the selected masking pattern has been used routinely in our clinical trials unit. Limitations We tested only five fictitious identities, five individuals who completed forms, and three who checked forms. Also, we initially considered only four patterns and variations in them. Conclusions We defined a masking pattern that satisfactorily fulfilled our needs for confidentiality. This and other procedures for remote preenrollment checking of consent form can be a key component of a risk-based monitoring strategy. © 2013 The Author(s).

Journot V.,French Institute of Health and Medical Research | Perusat-Villetorte S.,French Institute of Health and Medical Research | Bouyssou C.,French Institute of Health and Medical Research | Couffin-Cadiergues S.,ANRS | And 3 more authors.
Clinical Trials | Year: 2013

Background In biomedical research, the signed consent form must be checked for compliance with regulatory requirements. Checking usually is performed on site, most frequently after a participants final enrollment. Purpose We piloted a procedure for remote preenrollment consent forms checking. We applied it in five trials and assessed its efficiency to reduce form nonconformity before participant enrollment. Methods Our clinical trials unit (CTU) routinely uses a consent form with an additional copy that contains a pattern that partially masks the participants name and signature. After completion and signatures by the participant and investigator, this masked copy is faxed to the CTU for checking. In case of detected nonconformity, the CTU suspends the participants enrollment until the form is brought into compliance. We checked nonconformities of consent forms both remotely before enrollment and on site in five trials conducted in our CTU. We tabulated the number and nature of nonconformities by location of detection: at the CTU or on site. We used these data for a pseudo before-and-after analysis and estimated the efficiency of this remote checking procedure in terms of reduction of nonconformities before enrollment as compared to the standard on-site checking procedure. We searched for nonconformity determinants among characteristics of trials, consent forms, investigator sites, and participants through multivariate logistic regression so as to identify opportunities for improvement in our procedure. Results Five trials, starting sequentially but running concurrently, with remote preenrollment and on-site checking of consent forms from 415 participants screened in 2006-2009 led to 518 consent forms checked; 94 nonconformities were detected in 75 forms, 75 (80%) remotely and 19 more (20%) on site. Nonconformities infrequently concerned dates of signatures (7%) and information about participants (12%). Most nonconformities dealt with investigator information (76%), primarily contact information (54%). The procedure reduced nonconformities by 81% (95% confidence interval (CI): 73%-89%) before enrollment. Nonconforming consent forms dropped from 25% to 0% over the period, indicating a rapid learning effect between trials. Fewer nonconformities were observed for participants screened later in a trial (odds ratio (95% CI): 0.5 (0.3-0.8); p = 0.004), indicating a learning effect within trials. Nonconformities were more common for participants enrolled after screening (2.4 (1.1-5.3); p = 0.03), indicating a stricter scrutiny by form checkers. Limitations Although our study had a pseudo before-and-after design, no major bias was identified. Power and generalizability of our findings were sufficient to support implementation in future trials. © 2013 The Author(s).

Journot V.,French Institute of Health and Medical Research | Pignon J.-P.,Institute Of Cancerologie Gustave Roussy | Gaultier C.,French Institute of Health and Medical Research | Daurat V.,Assistance Publique Hopitaux de Paris | And 11 more authors.
Contemporary Clinical Trials | Year: 2011

Context: Good Clinical Practice regulates monitoring activities in clinical research. Due to question and design diversity, and limited resources, on-site monitoring is often less intensive in the academic context, and variable. Standardization is needed, and relies on definition and validation of tools accounting for risk. Objective: To define, and validate tools, to implement a risk-based monitoring strategy for academic clinical research. Methods: Working groups of experienced professionals searched the literature, and built a consensus risk-assessment scale (RAS), and a risk-adapted monitoring plan (RAMP). We allocated 200 protocols to 49 assessors. We assessed the RAS relevance vs. a visual analogue scale (VAS), and its reproducibility through Kraemer's kappa, and intraclass correlation coefficient (ICC) from a random proportional odds model. We identified sources of disagreement through a logistic regression. We described assessors' difficulties during assessment. We applied the RAMP to 10 protocols per risk level, and rated its feasibility (0 = easy to 4 = impossible). Results: RAS and RAMP were defined in 4 levels. RAS relevance was good: RAS-risk levels were evenly distributed on VAS-risk (0.6, 2.6, 5.6, and 7.9). Reproducibility was moderate to good: kappa = 0.48, ICC = 0.70. Major disagreements (36%) arose from decision-makers, rather than hands-on managers. Most difficulties occurred in ill-written protocols (17%). RAMP was easily feasible for most protocols (mean score: 0.2 to 0.9). We proposed a standard synopsis for evaluation purpose. Conclusion: We defined, and validated risk-based tools. This risk-adapted strategy will be compared to an intensive one in a randomized trial, Optimon, to define a standard of practice for academic clinical research. © 2010 Elsevier Inc.

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