Enhancing clinical evidence by proactively building quality into clinical trials

Meeker-O’Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

doi:10.1177/1740774516643491

Cited by 48 publications

(44 citation statements)

References 13 publications

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“…Our framework thus sought to identify elements common to clinical trials that could be subject to earlier planning as well as to failureexamination and root-cause analyses. We also wanted to draw parallels to other CTTI activities, particularly those related to Quality by Design (QbD), aimed at improving trials at earlier stages [21,22]. The framework delineates three areas essential to recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication.…”

Section: Framework Development and Expert Meetingmentioning

confidence: 99%

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative

Huang

Bull

McKee

et al. 2018

Contemporary Clinical Trials

218

171

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Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement.

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Section: Framework Development and Expert Meetingmentioning

confidence: 99%

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative

Huang

Bull

McKee

et al. 2018

Contemporary Clinical Trials

218

171

View full text Add to dashboard Cite

show abstract

“…In both qualitative and quantitative results, local trial staff involvement in developing the protocol came up and was rated as the most helpful option for increasing protocol suitability. The importance of site staff involvement in trial planning has also been stressed in the literature [ 11 , 21 , 32 , 39 ]. Eastabrook et al state, “Given the important role of site staff for overall trial success it is critical to understand their preferences and experiences” [ 40 ], while Alsumidaie promotes trial site involvement to create clinical trials that work operationally while reducing risks [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…While feasibility of trial sites is routinely assessed, protocol suitability is a new concept and rarely considered. Meeker-O’Connell et al stress that improving protocol design, trial planning and quality oversight has a direct impact on inefficiencies like high costs and unsustainability [ 21 ]. With the rising complexity of trial protocols and the intense pressure on sponsors to accelerate development cycle times, suitability is becoming more important to alleviate execution burdens and ultimately improve trial conduct efficiency [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Increasing protocol suitability for clinical trials in sub-Saharan Africa: a mixed methods study

Vischer

Pfeiffer

Kealy

et al. 2017

glob health res policy

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BackgroundThe trial protocol is the most important document for clinical trials and describes not only the design and methodology of a study, but also all practical aspects. The suitability of the protocol has a direct impact on the execution and results of the trial. However, suitability is rarely addressed in trial practice and research. The aim of our study was to investigate protocol suitability and to identify suitability-enhancing measures for trials in sub-Saharan Africa.MethodsWe used an exploratory mixed methods design. First, we interviewed 36 trial staff at different organisational levels in Ghana, Burkina Faso and Senegal. Second, we conducted an online survey among trial staff in sub-Saharan Africa to investigate trial protocol suitability based on the main themes distilled from the interviews.ResultsProtocol suitability surfaced as a prominent topic in interviews with trial staff, critiqued for its lack of clarity, implementability and adaptation to trial participants as well as to the workforce and infrastructure available. Both qualitative and quantitative investigations identified local site staff involvement in protocol development as the most helpful mean of increasing protocol suitability. Careful assessment of the local context, capacity and cultures, and ensuring that staff understand the protocol were also cited as helpful measures.ConclusionsOur data suggests that protocol suitability can be increased by discussing and reviewing the protocol with trial staff in advance. Involving operationally experienced staff would be most useful. For multicentre trials, we suggest that at least one trial staff member from each of the sites with the highest expected recruitment rates be involved in developing the protocol. Carefully assessing the context prior to study start is indispensable to ensuring protocol suitability and should particularly focus on the workforce and infrastructure available, as well as the needs and availability of trial participants. To allow for protocol suitability enhancing measures, planners must allocate enough time for trial preparation and solicit feedback and information on context at an early stage. Such prospective planning would increase implementability, efficiency and quality of trials in the long run.Electronic supplementary materialThe online version of this article (doi:10.1186/s41256-017-0031-1) contains supplementary material, which is available to authorized users.

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“…and provide a feasibility score from options "Feasible and easy to achieve in current practice" (score 5), "Feasible but expensive or challenging" (4), "Not sure" (3), "Possible but cost or practical issues make it unworkable" (2), "Not possible at present" (1). We also asked respondents whether any of a pre-defined list of challenges might apply to implementing a given process: cost, time for trials unit staff, time for centre staff, logistical issues, legal or regulatory issues, other (specify).…”

Section: Stakeholder Consultation To Assess Feasibility Of Suggested mentioning

confidence: 99%

“…'errors that matter'. 1 The full methods and results are reported elsewhere. 17 TEMPER found that the majority of centres in both triggered visits and matched visits (those without concern) had at least one Major or Critical finding, questioning the efficacy of triggered monitoring as employed in these trials.…”

Section: Introductionmentioning

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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Enhancing clinical evidence by proactively building quality into clinical trials

Cited by 48 publications

References 13 publications

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative

Increasing protocol suitability for clinical trials in sub-Saharan Africa: a mixed methods 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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