Lessons Learned in Clinical Trial Communication During an Ebola Outbreak: The Implementation of STRIVE

Abstract Communication contributed to 4 important aspects of the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE): recruiting participants, supporting Human Subjects Protection, building trust in the community to support the trial, and mitigating the impact of rumors and misinformation. Communication was particularly important because STRIVE was Sierra Leone’s first vaccine clinical trial and was implemented during a public health emergency. Communication efforts began months prior to trial launch, building awareness and support through sensitization sessions with stakeholders and community leaders. Community engagement activities continued throughout the trial to maintain relationships with leaders and stakeholders and disseminate accurate information, fostering trust in the trial. The communication team led recruitment with hundreds of information sessions for potential participants, facilitating the informed consent process. Communication efforts continued post-enrollment, supporting ongoing voluntary participation in the trial. Informal formative activities during the trial yielded insights on participants’ perceptions and information needs. While Centers for Disease Control and Prevention Institutional Review Board–approved activities and materials did not change, this flexible strategy allowed for responsive interactions with participants. The trial success and its community acceptance illustrated STRIVE’s successful communications efforts, owing in large part to this flexibility and commitment to community engagement. Clinical Trials Registration ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

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In silico imaging clinical trials: cheaper, faster, better, safer, and more scalable

Trials ◽

10.1186/s13063-020-05002-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aldo Badano

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Medical Devices ◽

In Silico ◽

Lessons Learned ◽

Patient Access ◽

High Quality ◽

Virtual Imaging ◽

Regulatory Evaluation

AbstractImaging clinical trials can be burdensome and often delay patient access to novel, high-quality medical devices. Tools for in silico imaging trials have significantly improved in sophistication and availability. Here, I describe some of the principal advantages of in silico imaging trials and enumerate five lessons learned during the design and execution of the first all-in silico virtual imaging clinical trial for regulatory evaluation (the VICTRE study).

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Impact of patient and public involvement on enrolment and retention in clinical trials: systematic review and meta-analysis

BMJ ◽

10.1136/bmj.k4738 ◽

2018 ◽

pp. k4738 ◽

Cited By ~ 67

Author(s):

Joanna C Crocker ◽

Ignacio Ricci-Cabello ◽

Adwoa Parker ◽

Jennifer A Hirst ◽

Alan Chant ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trial ◽

Clinical Trials ◽

Lived Experience ◽

Odds Ratio ◽

Public Involvement ◽

Meta Analysis ◽

Patient And Public Involvement ◽

Retention Rates ◽

The Impact

AbstractObjectiveTo investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI.DesignSystematic review and meta-analysis.Data sourcesTen electronic databases, including Medline, INVOLVE Evidence Library, and clinical trial registries.Eligibility criteriaExperimental and observational studies quantitatively evaluating the impact of a PPI intervention, compared with no intervention or non-PPI intervention(s), on participant enrolment and/or retention rates in a clinical trial or trials. PPI interventions could include additional non-PPI components inseparable from the PPI (for example, other stakeholder involvement).Data extraction and analysisTwo independent reviewers extracted data on enrolment and retention rates, as well as on the context and characteristics of PPI intervention, and assessed risk of bias. Random effects meta-analyses were used to determine the average effect of PPI interventions on enrolment and retention in clinical trials: main analysis including randomised studies only, secondary analysis adding non-randomised studies, and several exploratory subgroup and sensitivity analyses.Results26 studies were included in the review; 19 were eligible for enrolment meta-analysis and five for retention meta-analysis. Various PPI interventions were identified with different degrees of involvement, different numbers and types of people involved, and input at different stages of the trial process. On average, PPI interventions modestly but significantly increased the odds of participant enrolment in the main analysis (odds ratio 1.16, 95% confidence interval and prediction interval 1.01 to 1.34). Non-PPI components of interventions may have contributed to this effect. In exploratory subgroup analyses, the involvement of people with lived experience of the condition under study was significantly associated with improved enrolment (odds ratio 3.14v1.07; P=0.02). The findings for retention were inconclusive owing to the paucity of eligible studies (odds ratio 1.16, 95% confidence interval 0.33 to 4.14), for main analysis).ConclusionsThese findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study. Further research is needed to assess which types of PPI work best in particular contexts, the cost effectiveness of PPI, the impact of PPI at earlier stages of trial design, and the impact of PPI interventions specifically targeting retention.Systematic review registrationPROSPERO CRD42016043808.

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Managing Clinical Trials for Alzheimer’s Disease During the COVID-19 Crisis: Experience at Fundació ACE in Barcelona, Spain

Journal of Alzheimer s Disease ◽

10.3233/jad-200750 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1805-1813

Author(s):

Carla Abdelnour ◽

Ester Esteban de Antonio ◽

Alba Pérez-Cordón ◽

Asunción Lafuente ◽

Mar Buendía ◽

...

Keyword(s):

Clinical Trials ◽

Ad Hoc ◽

Strategic Plan ◽

Lessons Learned ◽

Drop Out ◽

Rt Pcr ◽

Serological Tests ◽

Clinical Trial Research ◽

Research Activities ◽

The Impact

Background: The COVID-19 pandemic has brought great disruption to health systems worldwide. This affected ongoing clinical research, particularly among those most vulnerable to the pandemic, like dementia patients. Fundació ACE is a research center and memory clinic based in Barcelona, Spain, one of the hardest-hit countries. Objective: To describe the ad-hoc strategic plan developed to cope with this crisis and to share its outcomes. Methods: We describe participants’ clinical and demographic features. Additionally, we explain our strategic plan aimed at minimizing the impact on clinical trial research activities, which included SARS-CoV-2 RT-PCR and IgG serological tests to all participants and personnel. The outcomes of the plan are described in terms of observed safety events and drop-outs during the study period. Results: A total of 130 patients were participating in 16 active clinical trials in Fundació ACE when the lockdown was established. During the confinement, we performed 1018 calls to the participants, which led to identify adverse events in 26 and COVID-19 symptoms in 6. A total of 83 patients (64%) could restart on-site visits as early as May 11, 2020. All SARS-CoV-2 RT-PCR diagnostic tests performed before on-site visits were negative and only three IgG serological tests were positive. Throughout the study period, we only observed one drop-out, due to an adverse event unrelated to COVID-19. Discussion: The plan implemented by Fundació ACE was able to preserve safety and integrity of ongoing clinical trials. We must use the lessons learned from the pandemic and design crisis-proof protocols for clinical trials.

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The efficiency of single institutional review board review in National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network–initiated clinical trials

Clinical Trials ◽

10.1177/1740774518807888 ◽

2018 ◽

Vol 16 (1) ◽

pp. 3-10 ◽

Cited By ~ 3

Author(s):

Michael P Diamond ◽

Esther Eisenberg ◽

Hao Huang ◽

Christos Coutifaris ◽

Richard S Legro ◽

...

Keyword(s):

Clinical Trials ◽

Child Health ◽

Clinical Research ◽

Human Development ◽

Reproductive Medicine ◽

Institutional Review Board ◽

Institutional Review Boards ◽

Institutional Review ◽

The Impact ◽

Review Boards

Background/aims: Timely review of research protocols by institutional review boards leads to more rapid initiation of clinical trials, which is critical to expeditious translation from bench to bedside. This observational study examined the impact of a single institutional review board on time and efforts required to initiate clinical trials by the National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network. Methods: Collection of data from the same six main clinical sites for three current clinical trials and two past clinical trials, including time from institutional review board submission to approval, pages submitted, consent form length, number of required attachments, other regulatory requirements, order of review at central or local sites, and language in documents at individual participating sites. Results from two past clinical trials were also included. Results: While time required for actual institutional review board submission’s review and initial approval was reduced with use of a single institutional review board for multicenter trials (from a mean of 66.7–24.0 days), total time was increased (to a mean of 111.2 or 123.3 days). In addition to single institutional review board approval, all institutions required local approval of some components (commonly consent language and use of local language), which varied considerably. The single institutional review board relied on local institutions for adding or removing personnel, conflict of interest review, and auditing of activities. Conclusion: A single institutional review board reduced time for initial review and approval of protocols and informed consents, although time for the entire process was increased, as individual institutions retained oversight of components of required regulatory review. In order to best achieve the National Institute of Health’s goals for improved efficiency in initiation and conduct of multisite clinical research, greater coordination with local institutional review boards is key to streamlining and accelerating initiation of multisite clinical research.

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The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis

Health and Quality of Life Outcomes ◽

10.1186/s12955-019-1220-z ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 12

Author(s):

Samantha Cruz Rivera ◽

Derek G. Kyte ◽

Olalekan Lee Aiyegbusi ◽

Anita L. Slade ◽

Christel McMullan ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trial ◽

Clinical Trials ◽

Case Studies ◽

Real World ◽

Clinical Trial Data ◽

Research Impact ◽

Trial Data ◽

Patient Reported ◽

The Impact

Abstract Background Patient-reported outcomes (PROs) are commonly collected in clinical trials and should provide impactful evidence on the effect of interventions on patient symptoms and quality of life. However, it is unclear how PRO impact is currently realised in practice. In addition, the different types of impact associated with PRO trial results, their barriers and facilitators, and appropriate impact metrics are not well defined. Therefore, our objectives were: i) to determine the range of potential impacts from PRO clinical trial data, ii) identify potential PRO impact metrics and iii) identify barriers/facilitators to maximising PRO impact; and iv) to examine real-world evidence of PRO trial data impact based on Research Excellence Framework (REF) impact case studies. Methods Two independent investigators searched MEDLINE, EMBASE, CINAHL+, HMIC databases from inception until December 2018. Articles were eligible if they discussed research impact in the context of PRO clinical trial data. In addition, the REF 2014 database was systematically searched. REF impact case studies were included if they incorporated PRO data in a clinical trial. Results Thirty-nine publications of eleven thousand four hundred eighty screened met the inclusion criteria. Nine types of PRO trial impact were identified; the most frequent of which centred around PRO data informing clinical decision-making. The included publications identified several barriers and facilitators around PRO trial design, conduct, analysis and report that can hinder or promote the impact of PRO trial data. Sixty-nine out of two hundred nine screened REF 2014 case studies were included. 12 (17%) REF case studies led to demonstrable impact including changes to international guidelines; national guidelines; influencing cost-effectiveness analysis; and influencing drug approvals. Conclusions PRO trial data may potentially lead to a range of benefits for patients and society, which can be measured through appropriate impact metrics. However, in practice there is relatively limited evidence demonstrating directly attributable and indirect real world PRO-related research impact. In part, this is due to the wider challenges of measuring the impact of research and PRO-specific issues around design, conduct, analysis and reporting. Adherence to guidelines and multi-stakeholder collaboration is essential to maximise the use of PRO trial data, facilitate impact and minimise research waste. Trial registration Systematic Review registration PROSPERO CRD42017067799.

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Patient Income Level and Cancer Clinical Trial Participation

Journal of Clinical Oncology ◽

10.1200/jco.2012.45.4553 ◽

2013 ◽

Vol 31 (5) ◽

pp. 536-542 ◽

Cited By ~ 114

Author(s):

Joseph M. Unger ◽

Dawn L. Hershman ◽

Kathy S. Albain ◽

Carol M. Moinpour ◽

Judith A. Petersen ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Universal Access ◽

Participation Rate ◽

Treatment Decision ◽

Trial Participation ◽

Lower Income ◽

Clinical Trial Participation ◽

Clinical Trial Results ◽

The Impact

Purpose Studies have shown an association between socioeconomic status (SES) and quality of oncology care, but less is known about the impact of patient SES on clinical trial participation. Patients and Methods We assessed clinical trial participation patterns according to important SES (income, education) and demographic factors in a large sample of patients surveyed via an Internet-based treatment decision tool. Logistic regression, conditioning on type of cancer, was used. Attitudes toward clinical trials were assessed using prespecified items about treatment, treatment tolerability, convenience, and cost. Results From 2007 to 2011, 5,499 patients were successfully surveyed. Forty percent discussed clinical trials with their physician, 45% of discussions led to physician offers of clinical trial participation, and 51% of offers led to clinical trial participation. The overall clinical trial participation rate was 9%. In univariate models, older patients (P = .002) and patients with lower income (P = .001) and education (P = .02) were less likely to participate in clinical trials. In a multivariable model, income remained a statistically significant predictor of clinical trial participation (odds ratio, 0.73; 95% CI, 0.57 to 0.94; P = .01). Even in patients age ≥ 65 years, who have universal access to Medicare, lower income predicted lower trial participation. Cost concerns were much more evident among lower-income patients (P < .001). Conclusion Lower-income patients were less likely to participate in clinical trials, even when considering age group. A better understanding of why income is a barrier may help identify ways to make clinical trials better available to all patients and would increase the generalizability of clinical trial results across all income levels.

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PO 8300 REGIONAL CENTER FOR REGULATORY EXCELLENCE IN CLINICAL TRIAL OVERSIGHT – TRAINING 2017

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.71 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A28.1-A28

Author(s):

Delese Darko ◽

Yvonne Adu-Boahen

Keyword(s):

Public Health ◽

Clinical Trial ◽

Clinical Trials ◽

Good Clinical Practice ◽

Training Programme ◽

Fellowship Training ◽

Training Methods ◽

Health Technologies ◽

Trial Oversight ◽

The Impact

BackgroundThe competencies of the various national medicines regulatory agencies (NMRAs) in Africa vary which leads to generally porous regulatory systems for clinical trial oversight. Consequently, many trials have been conducted under unacceptable conditions compromising participants’ safety and data credibility and resulted in questionable outcomes that are used for making scientific judgement in addressing issues of public health in Africa.To improve the safety and quality of health technologies in Africa, the New Partnership for African Development (NEPAD) agency launched a programme to designate Regional Centres of Regulatory Excellence (RCOREs) with the specific objective of bridging existing gaps between African NMRAs through strengthening regulatory capacity of African Union member states. The Food and Drugs Authority (FDA), Ghana, was designated as RCORE for Clinical Trials oversight in May 2014.MethodsTo achieve the RCORE objectives, the FDA collaborated with the School of Public Health (SPH), University of Ghana to develop a training manual and piloted a training programme with funds from the International AIDS Vaccine Initiative (IAVI) through NEPAD.The programme, consisting of 4 compulsory modules, was organised from 6–30 November 2017 for 10 participants from Zambia, Sierra Leone, Liberia, Rwanda and Ghana. Interactive training methods in the form of theoretical and practical sessions were employed.ResultsThe pilot RCORE training was successful with expected training objectives achieved. Participants gained hands-on experience through activities like observing Good Clinical Practice inspection and a Technical Advisory Committee Meeting. Participants were given template tools to assist in developing regulatory guidelines and forms in their respective countries.A follow-up questionnaire was circulated to participants to assess the impact of the training on their work. Feedback indicates that regulation of clinical trials has improved in their respective institutions.ConclusionThis pilot fellowship training was successful, leading to the improvement of clinical trial regulation in the participating countries.

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Methodological Characteristics of Clinical Trials: Impact of Mandatory Trial Registration

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps30360 ◽

2019 ◽

Vol 22 ◽

pp. 131-141

Author(s):

Ashish Kumar Kakkar ◽

Biswa Mohan Padhy ◽

Sudhir Chandra Sarangi ◽

Yogendra Kumar Gupta

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Statistical Methods ◽

Quality Characteristics ◽

Allocation Concealment ◽

Trial Registration ◽

Control Group ◽

Study Protocols ◽

The Impact

Purpose: Numerous studies across multiple specialties have evaluated the impact of trial registration on quality of study reports and found significant improvements over several domains. However, the impact of mandatory trial registration on the quality of clinical trial protocols remains hitherto unexplored. Methods: We carried out a retrospective cohort study of clinical trial applications submitted to drug regulatory authority of India for initial review with the objective of comparing methodological characteristics of their protocols. Since trial registration was made mandatory in the country in June 2009, we selected two study periods as between January 2007 to May 2009 (Period I) and July 2009 to December 2011 (Period II). Seventy-five protocols were randomly selected using a computer-generated list for each study period, making a total of 150 protocols. Data on twelve key methodological characteristics were collected including clearly defined primary outcomes, randomization, blinding, use of control group, statistical methods, handling of withdrawals amongst others. Results: More than 3/4th of the trial applications in the two study periods were for new chemical entities and nearly 90% were pharmaceutical industry sponsored studies. Comparing the period before and after implementation of mandatory trial registration, description of clearly defined trial outcomes improved from nearly 42% to 80% (p<0.001), sample size justifications increased from 38% to 70% (p<0.001) and use of allocation concealment improved from 24% to 49% (p=0.001). Marked improvement was also noted for blinding, description of statistical methods and handling of withdrawals and dropouts. Remaining characteristics did not change significantly between the two study periods. The mean cumulative scores for the study protocols improved significantly from 7± 0.296 in the first period to 8.93± 0.346 (p<0.001) in the second period. Conclusions: Our study found a significant improvement in the methodological quality characteristics of the protocols particularly in elements related to minimization of bias and statistical methods, which could be attributed to mandatory trial registration. Overall, the significant improvement was limited to global clinical trials, and room for improvement was noted for two quality characteristics – proportion of randomized studies and trials adequately describing the generation of allocation sequence.

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