Dataset Information

Assessing site performance in the Altair study, a multinational clinical trial.

ABSTRACT: Reviewing clinical trial site performance identifies strategies to control outcomes. Performance across 5 geographical regions (36 sites across Asia, Australia, Europe, North America and Latin America) was investigated in a study that randomised 322 HIV-infected individuals.Regional performance was compared using descriptive analysis for time to site opening, recruitment, quality of data and laboratory samples. Follow-up consisted of 10 visits (96 weeks), electronic data collection (EDC) within 7 days of a visit and serious adverse events (SAEs) reported within 24 hours of site awareness.Median days to site opening was 250 (188 to 266), ranging from 177 (158 to 200) (Australia) to 265 (205 to 270) (Europe). Median days to ethics and regulatory approval was 182 (120 to 241) and 218 (182 to 341) days, respectively. Within regions, time to approval ranged from 187 (91 to 205) days (Australia) to 276 (175 to 384) days (Europe). Time to first randomisation ranged from 282 (250 to 313) days (Australia) to 426 (420 to 433) days (North America). Recruitment was lower than forecasted in Asia, Australia, Europe and North America at 89%, 77%, 91% and 43%, respectively. The converse was true in Latin America where despite ethics, regulatory and contractual delays, recruitment was 104% of predicted. Median days to EDC was 7 (3 to 16), ranging from 3 (1 to 16) (Asia) to 13 (8 to 14) days (North America). Median days for initial SAE submission to sponsor was 6 (2 to 20), ranging from 4 (2 to 18) (Latin America) to 24 (5 to 46) days (Australia). Sites took longer to submit final reports, overall median of 28 (7 to 91) days, ranging from 7 days (Australia) to 67 (23 to 103) days (Europe).Population availability and time to ethics and regulatory approvals influence recruitment; therefore accurate feasibility assessments are critical to site selection. Time to ethics and regulatory approval may not limit site inclusion if compensated by rapid recruitment. Identifying potential delays and methods for reduction can decrease time and costs for sponsors.Clinical Trials.Gov identifier: NCT00335322. Date of registration: 8 June 2006.

SUBMITTER: Berthon-Jones N

PROVIDER: S-EPMC4412197 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Assessing site performance in the Altair study, a multinational clinical trial.

Berthon-Jones Nisha N Courtney-Vega Kymme K Donaldson Anna A Haskelberg Hila H Emery Sean S Puls Rebekah R

Trials 20150408

<h4>Background</h4>Reviewing clinical trial site performance identifies strategies to control outcomes. Performance across 5 geographical regions (36 sites across Asia, Australia, Europe, North America and Latin America) was investigated in a study that randomised 322 HIV-infected individuals.<h4>Methods</h4>Regional performance was compared using descriptive analysis for time to site opening, recruitment, quality of data and laboratory samples. Follow-up consisted of 10 visits (96 weeks), elect ...[more]

PMID: 25872747

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Project description:BackgroundEvidence from prospectively designed studies to guide on-site monitoring practices for randomized trials is limited. A cluster randomized study, nested within the Strategic Timing of AntiRetroviral Treatment (START) trial, was conducted to evaluate on-site monitoring.MethodsSites were randomized to either annual on-site monitoring or no on-site monitoring. All sites were centrally monitored, and local monitoring was carried out twice each year. Randomization was stratified by country and projected enrollment in START. The primary outcome was a participant-level composite outcome including components for eligibility errors, consent violations, use of antiretroviral treatment not recommended by protocol, late reporting of START primary and secondary clinical endpoints (defined as the event being reported more than 6 months from occurrence), and data alteration and fraud. Logistic regression fixed effect hierarchical models were used to compare on-site versus no on-site monitoring for the primary composite outcome and its components. Odds ratios and 95% confidence intervals comparing on-site monitoring versus no on-site monitoring are cited.ResultsIn total, 99 sites (2107 participants) were randomized to receive annual on-site monitoring and 97 sites (2264 participants) were randomized to be monitored only centrally and locally. The two monitoring groups were well balanced at entry. In the on-site monitoring group, 469 annual on-site monitoring visits were conducted, and 134 participants (6.4%) in 56 of 99 sites (57%) had a primary monitoring outcome. In the no on-site monitoring group, 85 participants (3.8%) in 34 of 97 sites (35%) had a primary monitoring outcome (odds ratio = 1.7; 95% confidence interval: 1.1-2.7; p = 0.03). Informed consent violations accounted for most outcomes in each group (56 vs 41 participants). The largest odds ratio was for eligibility violations (odds ratio = 12.2; 95% confidence interval: 1.8-85.2; p = 0.01). The number of participants with a late START primary endpoint was similar for each monitoring group (23 vs 16 participants). Late START grade 4 and unscheduled hospitalization events were found for 34 participants in the on-site monitoring group and 19 participants in the no on-site monitoring group (odds ratio = 2.0; 95% confidence interval: 1.1-3.7; p = 0.02). There were no cases of data alteration or fraud. Based on the travel budget for on-site monitoring and the hours spent conducting on-site monitoring, the estimated cost of on-site monitoring was over US$2 million.ConclusionOn-site monitoring led to the identification of more eligibility and consent violations and START clinical events being reported more than 6 months from occurrence as compared to no on-site monitoring. Considering the nature of the excess monitoring outcomes identified at sites receiving on-site monitoring, as well as the cost of on-site monitoring, the value to the START study was limited.

Project description:BackgroundMulticentre randomised trials provide some of the key evidence underpinning healthcare practice around the world. They are also hard work and generally expensive. Some of this work and expense are devoted to sites that fail to recruit as many participants as expected. Methods to identify sites that will recruit to target would be helpful.MethodsWe asked trial managers at the Centre for Healthcare Randomised Trials (CHaRT), University of Aberdeen to predict whether a site would recruit to target. Predictions were made after a site initiation visit and were collected on a form comprising a simple 'Yes/No' prediction and a reason for the prediction. We did not provide guidance as to what trial managers might want to think about when making predictions. After a minimum of eight months of recruitment at each site for which a prediction had been made, all trial mangers in CHaRT were invited to a group discussion where predictions were presented together with sites' actual recruitment performance over that period. Individual trial managers reflected on their predictions and there was a general discussion about predicting site recruitment. The prediction reasons from the forms and the content of the group discussion were used to identify features linked to correct predictions of recruitment failure.ResultsTen trial managers made predictions for 56 site visits recruiting to eight trials. Trial managers' sensitivity was 82% and their specificity was 32%, correctly identifying 65% of sites that would hit their recruitment target and 54% of those that did not. Eight 'red flags' for recruitment failure were identified: previous poor site performance; slow approvals process; strong staff/patient preferences; the site recruitment target; the trial protocol and its implementation at the site; lack of staff engagement; lack of research experience among site staff; and busy site staff. We used these red flags to develop a guided prediction form.ConclusionsTrial managers' unguided recruitment predictions were not bad but were not good enough for decision-making. We have developed a modified prediction form that includes eight flags to consider before making a prediction. We encourage anyone interested in contributing to its evaluation to contact us.

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Assessing site performance in the Altair study, a multinational clinical trial.

Publications

Assessing site performance in the Altair study, a multinational clinical trial.

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