scholarly journals Protecting clinical trials in cystic fibrosis during the SARS-CoV-2 pandemic: risks and mitigation measures

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Silke van Koningsbruggen-Rietschel ◽  
Fiona Dunlevy ◽  
Veerle Bulteel ◽  
Kate Hayes ◽  
Anne Verbrugge ◽  
...  

AbstractThe SARS-CoV-2 pandemic has disrupted clinical trials worldwide. The European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) has tracked clinical trial disruption by surveying its 58 trial sites across 17 European countries and collated information on measures to mitigate the impact of the pandemic and ensure trial continuity. Here, we present recommendations on how to reduce the risk of SARS-CoV-2 exposure to patients and trial staff by implementing remote trial visits where possible, using home assessments, video and phone calls, electronic consent, and home delivery of study drugs. We discuss the practicalities of remote source data verification, protocol amendments, changing trial site location, and staff absences and home working. We outline recommendations on how to protect trial outcomes, including home assessments, safety reporting, protocol deviations, and recruitment challenges. Finally, we discuss the importance of continued access to study drugs via extension trials for some patients. This guidance was co-created from the shared knowledge and experience of sites in our network and was re-distributed directly to all ECFS-CTN sites to help mitigate the impact of further waves of the SARS-CoV-2 pandemic. We will also use this guidance to assist companies, academia, and consortia with future protocol design and risk mitigation plans. This guidance can be applied to clinical trials in other diseases and could help sites that are not supported by clinical trial networks.

2021 ◽  
Author(s):  
Silke van Koningsbruggen-Rietschel ◽  
Fiona Dunlevy ◽  
Veerle Bulteel ◽  
Kate Hayes ◽  
Anne Verbrugge ◽  
...  

Abstract The SARS-CoV-2 pandemic has disrupted clinical trials worldwide. The European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) has tracked clinical trial disruption by surveying its 58 trial sites across 17 European countries and collated information on measures to mitigate the impact of the pandemic and ensure trial continuity. Here we present recommendations on how to reduce the risk of SARS-CoV-2 exposure to patients and trial staff by implementing remote trial visits where possible, using home assessments, video and phone calls, electronic consent and home delivery of study drug. We discuss the practicalities of remote source data verification, protocol amendments, changing trial site location, and staff absences and home working. We outline how to protect trial outcomes, including home assessments, safety reporting, protocol deviations and recruitment challenges. Finally, we discuss the importance of continued access to study drug via extension trials for some patients. This guidance was co-created from the shared knowledge and experience of sites in our network and was re-distributed directly to all ECFS-CTN sites to help mitigate the impact of further waves of the SARS-CoV-2 pandemic. We will also use this guidance to assist companies, academia and consortia with future protocol design and risk mitigation plans.


BMJ ◽  
2018 ◽  
pp. k4738 ◽  
Author(s):  
Joanna C Crocker ◽  
Ignacio Ricci-Cabello ◽  
Adwoa Parker ◽  
Jennifer A Hirst ◽  
Alan Chant ◽  
...  

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.


Author(s):  
Samantha Cruz Rivera ◽  
Derek G. Kyte ◽  
Olalekan Lee Aiyegbusi ◽  
Anita L. Slade ◽  
Christel McMullan ◽  
...  

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.


2013 ◽  
Vol 31 (5) ◽  
pp. 536-542 ◽  
Author(s):  
Joseph M. Unger ◽  
Dawn L. Hershman ◽  
Kathy S. Albain ◽  
Carol M. Moinpour ◽  
Judith A. Petersen ◽  
...  

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.


2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A28.1-A28
Author(s):  
Delese Darko ◽  
Yvonne Adu-Boahen

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.


2019 ◽  
Vol 22 ◽  
pp. 131-141
Author(s):  
Ashish Kumar Kakkar ◽  
Biswa Mohan Padhy ◽  
Sudhir Chandra Sarangi ◽  
Yogendra Kumar Gupta

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.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4191-4191 ◽  
Author(s):  
Helene Caillon ◽  
Michel Attal ◽  
Philippe Moreau ◽  
Thomas Dejoie

Abstract Background: Detection and/or measurement of monoclonal components by serum protein electrophoresis (SPE) is essential for evaluation of response in multiple myeloma according to the International Myeloma Working Group (IMWG) criteria. Patient peak on SPE has a single presentation due to the extreme heterogeneity of monoclonal components based on isotype of immunoglobulin (Ig), charge, polymerization, viscosity, precipitation … Regarding the Ig isotype, distribution of myelomas has been known for a long time with about 55 % of IgG myelomas, 25 % of IgA myelomas, and 15% of light chain multiple myelomas (LCMM). Therefore differences in terms of various physical and chemical characteristics are observed according to isotype such as half-lives (IgG : 7-21 days ; IgA : 6 days ; only a few hours for light chains of Ig). Considering both differences about frequency and clearance according to Ig isotype, we addressed the question of the impact of isotype on the speed of response in multiple myeloma. Objective: The aim of this study was to assess if the different isotypes of monoclonal components involved in multiple myeloma have an impact on the velocity and the depth of response. Design and methods: Data from two recent clinical trials conducted by IFM were analysed. The first analysis was based on patients enrolled in the IFM DFCI 2009 clinical trial who benefited of each of the three MRD points planned in this trial (after induction and autograft for one arm, pre-maintenance and post-maintenance). Patients were categorized on the isotype of the monoclonal component involved : IgG, IgA or IgD intact immunoglobulin multiple myelomas (IIMM) with serum measurable disease according to IMWG criteria (i.e. serum monoclonal peak ≥ 10 g/L), LCMM, and IIMM without any serum measurable disease (i.e. serum monoclonal peak < 10 g/L).The percentage of patients who achieved at least a very good partial response (VGPR) was evaluated globally as well as for each category defined. The same analysis was carried out for the IFM 2013-04 clinical trial with one response assessment, after four induction cycles. Results: Concerning IFM DFCI 2009 trial, 398 patients evaluated on the three MRD points could be included in this analysis, divided into 185 and 213 in each arm of treatment. Within the total enrolment, two types of response kinetics could be distinguished : for IgA, IgD IIMM, IIMM without serum measurable disease and LCMM, the gain of response between post-induction +/- autograft and post-maintenance is on average 11,1 points (6,7 - 15) when IgG myelomas presented a difference of VGPR percentage of 27,9 points. The same observation could be made for each arm of treatment : 16,6 and 5,8 points of VGPR percentage gained in each arm for the "faster response" group as defined previously, whereas 33,3 and 23,3 points were gained for IgG myelomas. Apart from this difference of kinetics, we notably observed that IgG myelomas never reached VGPR rates obtained with other isotype myelomas. About IFM 2013-04 trial, 264 patients could be evaluated in our analysis after four cycles of VTD (131) or VCD (133) for induction. 98,0% of IgA myelomas achieved at least VGPR after induction (96,3% for VTD arm and 100% for VCD arm) whereas only 50,6% for IgG myelomas (57,3% and 43,2%) and 68,3% for LCMM (46,7% for VTD arm and 80,8 for VCD arm). Conclusion: This study shows that time of evaluation is a key factor regarding the different speed of response for each isotype of Ig. IgA myelomas and LCMM have a faster response than IgG myelomas. IgG myelomas have a lower biochemical response than other isotype myelomas. Consequently, for an accurate interpretation of data in clinical trials, patients should be equally distributed in each arm of treatment according to their isotype. Ideally, to be compared, clinical trials should always have the same isotype distribution, especially when an early evaluation is performed such as after induction. Disclosures Attal: jansen: Honoraria; celgene: Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3073-3073
Author(s):  
Marc Ryan Matrana ◽  
Scott A. Tomlins ◽  
Kat Kwiatkowski ◽  
Khalis Mitchell ◽  
Jennifer Marie Suga ◽  
...  

3073 Background: Widespread integration of systematized next generation sequencing (NGS)-based precision oncology is hindered by numerous barriers. Hence, we developed the Strata trial (NCT03061305), a screening protocol to determine the impact of scaled precision oncology. Methods: We implemented no-cost NGS on formalin fixed paraffin embedded (FFPE) clinical samples for all patients with advanced tumors, a common portfolio of partnered therapeutic clinical trials, and robust infrastructure development across the Strata Precision Oncology Network. Results: Across the network of 17 centers, specimens from 8673/9222 (94%) patients were successfully tested in the Strata CLIA/CAP/NCI-MATCH accredited laboratory using comprehensive amplicon-based DNA and RNA NGS. Patients were tested with one of three StrataNGS test versions; the most recent panel assesses all classes of actionable alterations (mutations, copy number alterations, gene fusions, microsatellite instability, tumor mutation burden and PD-L1 expression). Median surface area of received FFPE tumor samples was 25mm2 (interquartile range 9-95mm2), and the median turnaround time from sample receipt to report was 6 business days. 2577 (27.9%) patients had highly actionable alterations, defined as alterations associated with within-cancer type FDA approved or NCCN guideline recommended therapies (1072 patients), NCI-MATCH trial arms (1467 patients), Strata-partnered therapeutic trials (327 patients), or specific alteration-matched FDA approved therapies in patients with cancers of unknown primary (71 patients). Of the 1467 patients matched to an NCI-MATCH trial arm, 15 enrolled. Of the 327 patients matched to one of nine Strata-partnered clinical trials, 77 (24%) were screen failures, while 250 (76%) have either enrolled or are being actively followed for enrollment upon progression. Conclusions: Through streamlined consent methods, electronic medical record queries, and high throughput laboratory testing at no cost to patients, we demonstrate that scaled precision oncology is feasible across a diverse network of healthcare systems when paired with access to relevant clinical trials. Clinical trial information: NCT03061305.


2018 ◽  
Vol 217 (suppl_1) ◽  
pp. S40-S47 ◽  
Author(s):  
Amy Callis ◽  
Victoria M Carter ◽  
Aparna Ramakrishnan ◽  
Alison P Albert ◽  
Lansana Conteh ◽  
...  

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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