Defining a Central Monitoring Capability: Sharing the Experience of TransCelerate BioPharma’s Approach, Part 1

Wilson, Brad; Provencher, Tom; Gough, J. Heward; Clark, Stephanie; Abdrachitov, Ramil; Roeck, Karolien de; Constantine, Sarah Jane; Knepper, David; Lawton, Andy

doi:10.1177/2168479014546335

Cited by 15 publications

(23 citation statements)

References 5 publications

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“…An evaluation tool was proposed to monitor individual site performance within a multicentre randomised trial.59 (ns)Intensity adjusted score (IAS) = IAS = IS0 + don x IS1 + doff x IS2 where: IS0 = score assigned for enrolling a new participant during the 6 month evaluation perioddon = number of days the participant was on the study medication during the evaluation perioddoff = number of days the participant was off the study medicationIS1 = intensity score for the days in which the participant is receiving study medicationIS2 = intensity score for the days in which the participant is off all study medicationISA is calculated for each participant and then summing scores across all participants, once during the evaluation period• Funding adjusted score = IAS divided by the amount awarded for total direct costs during the given time period• Summary quartiles = total number of new and continuing participants on study Sweetman, 2011 [23]Retrospective analysis of publications of 80 clinical trials on protocol violations reportingNot applicableOccurrence of protocol violations, defined as total number of protocol violations divided by the number of enrolled participants Thom, 2011 [12] a Report of a centre performance assessment tool used within a clinical trial network to assess individual site performanceNot applicable• Protocol adherence, defined as average rate of protocol violations per enrolled participant• Data quality, defined as average rate of edit checks per participant• Data timeliness, defined as the percentage of forms entered late• Time of starting after the first centre start date• Sum of protocol adherence, data quality, data timeliness and timeliness of study start-up to give overall rank• Timeliness of study start-up• Recruitment, defined as average percentage of participants contributed over all studies conducted (B)• Retention, defined as average percentage of participants with complete follow-up data (B)• Recruitment/retention, defined as sum of recruitment + retention to give overall rank (B)• Adherence/quality (A)• Quality of laboratory samples collected (A) Tudur Smith, 2014 [24]Paper describing monitoring methods using a ‘risk proportionate approach’ used by an individual clinical trials unitNot applicable• Consent form completion, defined as consent forms returned within 7 days of completion by sites.• Recruitment process, defined as frequency of eligible participants who do not provide consent.• Missing primary outcome data, defined as cumulative percentage of participants with missing primary outcome data at each site• SAEs, defined as cumulative percentage of participants with at least one SAE across the trial as a whole and at each site /measure of time, e.g. 1 month• Sum of all SAEs/sum of all follow-up for the trial• Sum of all follow-up at site x overall SAE rate for the trial• Visit dates, defined as time between actual date of visit versus expected date of visit• Case report form completion, defined as timely submission (A) Wilson, 2014 [25]Theoretical paper describing methods of monitoring the conduct of trialsNot applicable• Quality metric encompassing: average number of major audit findings per audited site; percentage per site of unreported, confirmed SAEs; number of significant protocol deviations p...…”

Section: Resultsmentioning

confidence: 99%

Monitoring performance of sites within multicentre randomised trials: a systematic review of performance metrics

Walker¹,

Turzanski²,

Whitham³

et al. 2018

Trials

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BackgroundLarge multicentre trials are complex and expensive projects. A key factor for their successful planning and delivery is how well sites meet their targets in recruiting and retaining participants, and in collecting high-quality, complete data in a timely manner. Collecting and monitoring easily accessible data relevant to performance of sites has the potential to improve trial management efficiency. The aim of this systematic review was to identify metrics that have either been proposed or used for monitoring site performance in multicentre trials.MethodsWe searched the Cochrane Library, five biomedical bibliographic databases (CINAHL, EMBASE, Medline, PsychINFO and SCOPUS) and Google Scholar for studies describing ways of monitoring or measuring individual site performance in multicentre randomised trials. Records identified were screened for eligibility. For included studies, data on study content were extracted independently by two reviewers, and disagreements resolved by discussion.ResultsAfter removing duplicate citations, we identified 3188 records. Of these, 21 were eligible for inclusion and yielded 117 performance metrics. The median number of metrics reported per paper was 8, range 1–16. Metrics broadly fell into six categories: site potential; recruitment; retention; data collection; trial conduct and trial safety.ConclusionsThis review identifies a list of metrics to monitor site performance within multicentre randomised trials. Those that would be easy to collect, and for which monitoring might trigger actions to mitigate problems at site level, merit further evaluation.

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Section: Resultsmentioning

confidence: 99%

Monitoring performance of sites within multicentre randomised trials: a systematic review of performance metrics

Walker¹,

Turzanski²,

Whitham³

et al. 2018

Trials

View full text Add to dashboard Cite

show abstract

“…23 Central monitoring also displaces resource within the trials unit from dedicated on-site monitors towards the database programmers and statisticians responsible for developing reports and reviewing data, and trial management staff responsible for following up highlighted issues. 24 Resolving these resourcing questions, perhaps partly through different financial arrangements with centres in trials that rely more on central monitoring, could be a necessary precursor to a more widespread adoption of central monitoring methods.…”

Section: Discussionmentioning

confidence: 99%

Assessing the potential for prevention or earlier detection of on-site monitoring findings from randomised controlled trials: Further analyses of findings from the prospective TEMPER triggered monitoring study

et al. 2020

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Background/Aims: Clinical trials should be designed and managed to minimise important errors with potential to compromise patient safety or data integrity, employ monitoring practices that detect and correct important errors quickly, and take robust action to prevent repetition. Regulators highlight the use of risk-based monitoring, making greater use of centralised monitoring and reducing reliance on centre visits. The TEMPER study was a prospective evaluation of triggered monitoring (a risk-based monitoring method), whereby centres are prioritised for visits based on central monitoring results. Conducted in three UK-based randomised cancer treatment trials of investigational medicine products with time-to-event outcomes, it found high levels of serious findings at triggered centre visits but also at visits to matched control centres that, based on central monitoring, were not of concern. Here, we report a detailed review of the serious findings from TEMPER centre visits. We sought to identify feasible, centralised processes which might detect or prevent these findings without a centre visit. Methods: The primary outcome of this study was the proportion of all ‘major’ and ‘critical’ TEMPER centre visit findings theoretically detectable or preventable through a feasible, centralised process. To devise processes, we considered a representative example of each finding type through an internal consensus exercise. This involved (a) agreeing the potential, by some described process, for each finding type to be centrally detected or prevented and (b) agreeing a proposed feasibility score for each proposed process. To further assess feasibility, we ran a consultation exercise, whereby the proposed processes were reviewed and rated for feasibility by invited external trialists. Results: In TEMPER, 312 major or critical findings were identified at 94 visits. These findings comprised 120 distinct issues, for which we proposed 56 different centralised processes. Following independent review of the feasibility of the proposed processes by 87 consultation respondents across eight different trial stakeholder groups, we conclude that 306/312 (98%) findings could theoretically be prevented or identified centrally. Of the processes deemed feasible, those relating to informed consent could have the most impact. Of processes not currently deemed feasible, those involving use of electronic health records are among those with the largest potential benefit. Conclusions: This work presents a best-case scenario, where a large majority of monitoring findings were deemed theoretically preventable or detectable by central processes. Caveats include the cost of applying all necessary methods, and the resource implications of enhanced central monitoring for both centre and trials unit staff. Our results will inform future monitoring plans and emphasise the importance of continued critical review of monitoring processes and outcomes to ensure they remain appropriate.

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“…Central monitoring also displaces resource within the trials unit from dedicated on-site monitors towards the database programmers and statisticians responsible for developing reports and reviewing data, and trial management staff responsible for following up highlighted issues. 23 Resolving these resourcing questions, perhaps partly through different financial arrangements with centres in trials that rely more on central monitoring, could be a necessary precursor to a more widespread adoption of central monitoring methods.…”

Section: Discussionmentioning

confidence: 99%

Assessing the potential for prevention or earlier detection of on-site monitoring findings from randomised controlled trials: further analyses of findings from the prospective TEMPER triggered monitoring study

Cragg

Hurley

Yorke-Edwards

et al. 2020

Preprint

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Background/Aims Clinical trials should be designed and managed to minimise important errors with potential to compromise patient safety or data integrity, employ monitoring practices that detect and correct important errors quickly, and take robust action to prevent repetition. Regulators highlight the use of risk-based monitoring, making greater use of centralised monitoring and reducing reliance on centre visits. The TEMPER study was a prospective evaluation of triggered monitoring (a risk-based monitoring method), whereby centres are prioritised for visits based on central monitoring results. Conducted in three UK-based randomised cancer treatment trials of investigational medicine products with time-to-event outcomes, it found high levels of serious findings at triggered centre visits but also at visits to matched control centres that, based on central monitoring, were not of concern. Here, we report a detailed review of the serious findings from TEMPER centre visits. We sought to identify feasible, centralised processes which might detect or prevent these findings without a centre visit. Methods We considered a representative example of each finding type through a three-staged consensus exercise. 1: Three trialists independently reviewed the issues and graded their potential for detection by central monitoring or prevention by some described process, each on a five-point scale. 2. Results of round 1 were shared anonymously and each trialist re-reviewed the list choosing whether or not to change their grading. 3. The three trialists discussed and agreed grades for any issues without consensus, and proposed a feasibility score for each proposed process. In a consultation exercise, the proposed processes were reviewed and rated for feasibility by an invited external trialist group. The primary outcome was the proportion of all major and critical findings theoretically detectable or preventable through a feasible, centralised process. Results In TEMPER, 312 major or critical findings were identified at 94 visits. These findings comprised 120 distinct issues, for which we proposed 56 different centralised processes. Following independent review of the feasibility of the proposed processes by 87 consultation respondents across different stakeholder groups, we conclude that 306/312 (98%) findings could theoretically be prevented or identified centrally. Conclusions This work presents a best-case scenario, where a large majority of monitoring findings were deemed theoretically preventable or detectable by central processes. Caveats include the cost of applying all necessary methods, and the resource implications of enhanced central monitoring for both centre and trials unit staff. Of processes not currently deemed feasible, use of electronic health records has the largest potential benefit. Our results will inform future monitoring plans and emphasise the importance of continued critical review of monitoring processes and outcomes to ensure they remain appropriate. Key words: monitoring, central monitoring, on-site monitoring, risk-based monitoring, efficient trial conduct

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Defining a Central Monitoring Capability: Sharing the Experience of TransCelerate BioPharma’s Approach, Part 1

Cited by 15 publications

References 5 publications

Monitoring performance of sites within multicentre randomised trials: a systematic review of performance metrics

Monitoring performance of sites within multicentre randomised trials: a systematic review of performance metrics

Assessing the potential for prevention or earlier detection of on-site monitoring findings from randomised controlled trials: Further analyses of findings from the prospective TEMPER triggered monitoring study

Assessing the potential for prevention or earlier detection of on-site monitoring findings from randomised controlled trials: further analyses of findings from the prospective TEMPER triggered monitoring study

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