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Trials Mar 2021Along with its heavy toll of morbidity and mortality, the coronavirus disease 2019 (COVID-19) pandemic exposed several limitations of the current global research... (Review)
Review
Along with its heavy toll of morbidity and mortality, the coronavirus disease 2019 (COVID-19) pandemic exposed several limitations of the current global research response. The slow and inefficient process of carrying out traditional randomized clinical trials led regulatory authorities to hastily approve treatments and tests without sufficient evidence of safety and efficacy.We here outline issues with the current research platform, summarize shortcomings of traditional randomized clinical trials particularly apparent at the time of pandemics, and highlight the advantages of pragmatic clinical trials as an alternative to rapidly generate the needed clinical evidence. We further discuss barriers and challenges to pragmatic clinical trials implementation and explore opportunities for research institutions and regulatory authorities to facilitate widespread adoption of this vital research tool.As a subsequent wave of COVID-19, and/or another epidemic, are all but inevitable in our lifetime, we must ensure that our research infrastructure is conducive to carrying out pragmatic clinical trials to expeditiously generate the needed evidence and blunt the epidemic's toll on human lives and livelihoods.
Topics: COVID-19; Drug Approval; Evidence-Based Medicine; Humans; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 33761968
DOI: 10.1186/s13063-021-05165-0 -
Rheumatic Diseases Clinics of North... May 2019Real-world evidence requires use of new tools and methods to support efficient evidence generation. Among those tools are pragmatic trials, utilization of central/single... (Review)
Review
Real-world evidence requires use of new tools and methods to support efficient evidence generation. Among those tools are pragmatic trials, utilization of central/single institutional review board and electronic consent, and data linkages between diverse types of data sources (eg, a trial or registry to administrative claims or electronic medical record data). This article reviews these topics in the context of describing several exemplar use cases specific to rheumatology and provides perspective regarding both the promise and potential pitfalls in using these tools and approaches.
Topics: Evidence-Based Medicine; Humans; Information Storage and Retrieval; Informed Consent; Pragmatic Clinical Trials as Topic; Research Design; Rheumatic Diseases; Telemedicine
PubMed: 30952398
DOI: 10.1016/j.rdc.2019.01.010 -
BMC Medical Research Methodology Aug 2019The paper opens with a brief history of two of the major intellectual components of the recent utilitarian turn in clinical research, namely 'pragmatic trials' and...
BACKGROUND
The paper opens with a brief history of two of the major intellectual components of the recent utilitarian turn in clinical research, namely 'pragmatic trials' and 'implementation science'. The two schools of thought developed independently and the paper scrutinises their mutual compatibilities and incompatibilities, asking: i) what do the leading advocates of pragmatic trials assume about the transfer of research findings to real-world practice and ii) what role pragmatic trials can and should play in the evaluation of implementation science strategies.
METHODS
The paper utilises 'explication de texte': i) providing a close reading of the inferential logics contained in major published expositions of the two paradigms, and ii) interrogating the conclusions of a pragmatic trial of an intervention providing guidelines on retinal screening aimed at family practitioners.
RESULTS
The paper is in two parts. Part 1 unearths some significant incommensurability - the pragmatic trial literature retains an antiquated view of knowledge transfer and is overly optimistic about the wide applicability the findings of pragmatic trials to 'real world' conditions. Part 2 of the paper outlines an empirical strategy to better penetrate the mechanisms of knowledge transfer and to tackle the issue of the generalisabilty of research findings in implementation science.
CONCLUSIONS
Pragmatism, classically, is about problem solving and the melding of perspectives. The core research requirement in implementation science is a fundamental shift from the narrow shoulders of pragmatic trials to a model of explanation building based upon a multi-case, multi-method body of evidence.
Topics: Biomedical Research; Evidence-Based Practice; Humans; Implementation Science; Pragmatic Clinical Trials as Topic; Reproducibility of Results; Research Design
PubMed: 31420024
DOI: 10.1186/s12874-019-0814-9 -
Contemporary Clinical Trials Aug 2022Home-based testing for COVID-19 has potential to reduce existing health care disparities among underserved populations in the United States. However, implementation of...
BACKGROUND
Home-based testing for COVID-19 has potential to reduce existing health care disparities among underserved populations in the United States. However, implementation of home-based tests in these communities may face significant barriers. This study evaluates the acceptability, feasibility, and success of home-based testing and the potential added benefit of active support from trusted community health workers for Native Americans and Hispanic/Latino adults living in rural Montana and Washington states.
METHODS/DESIGN
The academic-community research team designed the trial to be responsive to community needs for understanding barriers and supports to home-based COVID-19 testing. The "Protecting Our Community" study is a two-arm pragmatic randomized controlled trial in which a total of 400 participants are randomized to active or passive arms. Participants of both study arms receive a commercially available home collection COVID-19 test kit, which is completed by mailing a self-collected nasal swab to a central laboratory. The primary study outcome is return of the kit to the central lab within 14 days. The cultural, social, behavioral, and economic barriers to home-based COVID-19 testing are also assessed by qualitative research methods. A survey and semi-structured interviews are conducted after the trial to evaluate perceptions and experience of home-based testing.
DISCUSSION
Implementing home-based testing in underserved populations, including among Native American and Hispanic/Latino communities, may require additional support to be successful. The Protecting Our Community trial examines the effect of trusted community health workers on use of home-based testing, which may be adaptable for community-driven models of home-based testing in other underserved populations.
Topics: COVID-19; COVID-19 Testing; Hispanic or Latino; Humans; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; SARS-CoV-2; United States; American Indian or Alaska Native
PubMed: 35691487
DOI: 10.1016/j.cct.2022.106820 -
European Journal of Rheumatology Jul 2022The aim of this qualitative research was to identify physician-perceived patient and clinic barriers to patient recruitment in a rheumatoid arthritis (RA) pragmatic...
OBJECTIVE
The aim of this qualitative research was to identify physician-perceived patient and clinic barriers to patient recruitment in a rheumatoid arthritis (RA) pragmatic trial of anti-tumor necrosis factor (TNF) biologic versus non-TNF biologic/Janus-Kinase inhibitor initiation after an inadequate response to methotrexate.
METHODS
Semistructured telephone interviews were conducted with 26 rheumatologists in March 2019. An exploratory thematic analysis approach was used to analyze the interview data.
RESULTS
Physician perceived patient barriers to the implementation of an RA pragmatic trial. This theme covers three subthemes: (1) patients' personal barriers, (2) patients' treatment-related factors, and (3) trial-related factors (eg, patient recruitment, side effects, mode of use, etc). Physicians perceived clinic barriers interfered with the pragmatic trial enrollment from the clinic or the healthcare system perspective. This theme covered four subthemes: (1) clinic-related factors, (2) patient-related factors, (3) research personnel, and (4) facilitators (positive factors of the clinic).
CONCLUSION
Our results from the inductive thematic analysis will help researchers understand the key patient and clinic/system factors/barriers that may influence pragmatic RA trial implementation. The themes suggest there are factors that can be modified (eg, coordinator effort needed, effective patient recruitment during clinic visits, provider engagement) and challenges to overcome (patient insurance status, busy clinic flow, and space issues including limited number of patient rooms). In summary, these themes provide a basis for our and other research teams to develop clinic-centered and patientcentered strategies to implement a pragmatic RA trial.
Topics: Arthritis, Rheumatoid; Biological Products; Humans; Physician-Patient Relations; Physicians; Pragmatic Clinical Trials as Topic; Qualitative Research
PubMed: 35156626
DOI: 10.5152/eujrheum.2022.21038 -
Trials Aug 2022Alliance for Clinical Trials in Oncology (Alliance) coordinated trials utilize Medidata Rave® (Rave) as the primary clinical data capture system. A growing number of... (Review)
Review
Successes and lessons learned in database development for national multi-site cancer care delivery research trials: the Alliance for Clinical Trials in Oncology experience.
INTRODUCTION
Alliance for Clinical Trials in Oncology (Alliance) coordinated trials utilize Medidata Rave® (Rave) as the primary clinical data capture system. A growing number of innovative and complex cancer care delivery research (CCDR) trials are being conducted within the Alliance with the aims of studying and improving cancer-related care. Because these trials encompass patients, providers, practices, and their interactions, a defining characteristic of CCDR trials is multilevel data collection in pragmatic settings. Consequently, CCDR trials necessitated innovative strategies for database development, centralized data management, and data monitoring in the presence of these real-world multilevel relationships. Having real trial experience in working with community and academic centers, and having recently implemented five CCDR trials in Rave, we are committed to sharing our strategies and lessons learned in implementing such pragmatic trials in oncology.
METHODS
Five Alliance CCDR trials are used to describe our approach to analyzing the database development needs and the novel strategies applied to overcome the unanticipated challenges we encountered. The strategies applied are organized into 3 categories: multilevel (clinic, clinic stakeholder, patient) enrollment, multilevel quantitative and qualitative data capture, including nontraditional data capture mechanisms being applied, and multilevel data monitoring.
RESULTS
A notable lesson learned in each category was (1) to seek long-term solutions when developing the functionality to push patient and non-patient enrollments to their respective Rave study database that affords flexibility if new participant types are later added; (2) to be open to different data collection modalities, particularly if such modalities remove barriers to participation, recognizing that additional resources are needed to develop the infrastructure to exchange data between that modality and Rave; and (3) to facilitate multilevel data monitoring, orient site coordinators to the their trial's multiple study databases, each corresponding to a level in the hierarchy, and remind them to establish the link between patient and non-patient participants in the site-facing NCI web-based enrollment system.
CONCLUSION
Although the challenges due to multilevel data collection in pragmatic settings were surmountable, our shared experience can inform and foster collaborations to collectively build on our past successes and improve on our past failures to address the gaps.
Topics: Clinical Trials as Topic; Data Management; Databases, Factual; Health Services Research; Humans; Medical Oncology; Neoplasms
PubMed: 35945621
DOI: 10.1186/s13063-022-06536-x -
BMC Medical Research Methodology Jun 2023Pragmatic clinical trials (PCTs) are designed to reflect how an investigational treatment would be applied in clinical practice. As such, unlike their explanatory... (Review)
Review
BACKGROUND
Pragmatic clinical trials (PCTs) are designed to reflect how an investigational treatment would be applied in clinical practice. As such, unlike their explanatory counterparts, they measure therapeutic effectiveness and are capable of generating high-quality real-world evidence. However, the conduct of PCTs remains extremely rare. The scarcity of such studies has contributed to the emergence of the efficacy-effectiveness gap and has led to calls for launching more of them, including in the field of oncology. This analysis aimed to identify self-labelled pragmatic trials of antineoplastic interventions and to evaluate whether their use of this label was justified.
METHODS
We searched PubMed® and Embase® for publications corresponding with studies that investigated antitumor therapies and that were tagged as pragmatic in their titles, abstracts and/or index terms. Subsequently, we consulted all available source documents for the included trials and extracted relevant information from them. The data collected were then used to appraise the degree of pragmatism displayed by the PCTs with the help of the validated PRECIS-2 tool.
RESULTS
The literature search returned 803 unique records, of which 46 were retained upon conclusion of the screening process. This ultimately resulted in the identification of 42 distinct trials that carried the 'pragmatic' label. These studies examined eight different categories of neoplasms and were mostly randomized, open-label, multicentric, single-country trials sponsored by non-commercial parties. On a scale of one (very explanatory) to five (very pragmatic), the median PCT had a PRECIS-2 score per domain of 3.13 (interquartile range: 2.57-3.53). The most and least pragmatic studies in the sample had a score of 4.44 and 1.57, respectively. Only a minority of trials were described in sufficient detail to allow them to be graded across all domains of the PRECIS-2 instrument. Many of the studies examined also had features that arguably precluded them from being pragmatic altogether, such as being monocentric or placebo-controlled in nature.
CONCLUSION
PCTs of antineoplastic treatments are generally no more pragmatic than they are explanatory.
Topics: Humans; Antineoplastic Agents; Medical Oncology; Research Design; Pragmatic Clinical Trials as Topic
PubMed: 37355603
DOI: 10.1186/s12874-023-01975-9 -
Journal of Clinical Epidemiology Nov 2017Pragmatic trials offer the opportunity to obtain real-life data on the relative effectiveness and safety of a treatment before or after market authorization. This is the...
OBJECTIVE
Pragmatic trials offer the opportunity to obtain real-life data on the relative effectiveness and safety of a treatment before or after market authorization. This is the penultimate paper in a series of eight, describing the impact of design choices on the practical implementation of pragmatic trials.
STUDY DESIGN AND SETTING
This paper focuses on the practical challenges of collecting and reporting safety data and of monitoring trial conduct while maintaining routine clinical care practice.
CONCLUSION
Current ICH guidance recommends that all serious adverse events and all drug-related events must be reported in an interventional trial. In line with current guidance, we propose a risk-based approach to the collection of non-drug-related non-serious adverse events and even serious events not related to treatment based on the risk profile of the medicine/class in the patient population of interest. Different options available to support the collection and reporting of safety data while minimizing study-related follow-up visits are discussed. A risk-based approach to monitoring trial conduct is also discussed, highlighting the difference in the balance of risks likely to occur in a pragmatic trial compared to traditional clinical trials and the careful consideration that must be given to the mitigation and management of these risks to maintain routine care.
Topics: Data Collection; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Humans; Monitoring, Physiologic; Patient Safety; Pragmatic Clinical Trials as Topic
PubMed: 28502812
DOI: 10.1016/j.jclinepi.2017.05.004 -
Journal of Clinical Epidemiology Nov 2017Pragmatic trials can improve our understanding of how treatments will perform in routine practice. In a series of eight papers, the GetReal Consortium has evaluated the...
Pragmatic trials can improve our understanding of how treatments will perform in routine practice. In a series of eight papers, the GetReal Consortium has evaluated the challenges in designing and conducting pragmatic trials and their specific methodological, operational, regulatory, and ethical implications. The present final paper of the series discusses the operational and methodological challenges of data collection in pragmatic trials. A more pragmatic data collection needs to balance the delivery of highly accurate and complete data with minimizing the level of interference that data entry and verification induce with clinical practice. Furthermore, it should allow for the involvement of a representative sample of practices, physicians, and patients who prescribe/receive treatment in routine care. This paper discusses challenges that are related to the different methods of data collection and presents potential solutions where possible. No one-size-fits-all recommendation can be given for the collection of data in pragmatic trials, although in general the application of existing routinely used data-collection systems and processes seems to best suit the pragmatic approach. However, data access and privacy, the time points of data collection, the level of detail in the data, and the lack of a clear understanding of the data-collection process were identified as main challenges for the usage of routinely collected data in pragmatic trials. A first step should be to determine to what extent existing health care databases provide the necessary study data and can accommodate data collection and management. When more elaborate or detailed data collection or more structured follow-up is required, data collection in a pragmatic trial will have to be tailor-made, often using a hybrid approach using a dedicated electronic case report form (eCRF). In this case, the eCRF should be kept as simple as possible to reduce the burden for practitioners and minimize influence on routine clinical practice.
Topics: Data Collection; Electronic Health Records; Evidence-Based Medicine; Humans; Pragmatic Clinical Trials as Topic
PubMed: 28716504
DOI: 10.1016/j.jclinepi.2017.07.003 -
Multiple Sclerosis (Houndmills,... Apr 2024Pragmatic trials are increasingly recognized for providing real-world evidence on treatment choices. (Review)
Review
BACKGROUND
Pragmatic trials are increasingly recognized for providing real-world evidence on treatment choices.
OBJECTIVE
The objective of this study is to investigate the use and characteristics of pragmatic trials in multiple sclerosis (MS).
METHODS
Systematic literature search and analysis of pragmatic trials on any intervention published up to 2022. The assessment of pragmatism with PRECIS-2 (PRagmatic Explanatory Continuum Indicator Summary-2) is performed.
RESULTS
We identified 48 pragmatic trials published 1967-2022 that included a median of 82 participants (interquartile range (IQR) = 42-160) to assess typically supportive care interventions ( = 41; 85%). Only seven trials assessed drugs (15%). Only three trials (6%) included >500 participants. Trials were mostly from the United Kingdom ( = 18; 38%), Italy ( = 6; 13%), the United States and Denmark (each = 5; 10%). Primary outcomes were diverse, for example, quality-of-life, physical functioning, or disease activity. Only 1 trial (2%) used routinely collected data for outcome ascertainment. No trial was very pragmatic in all design aspects, but 14 trials (29%) were widely pragmatic (i.e. PRECIS-2 score ⩾ 4/5 in all domains).
CONCLUSION
Only few and mostly small pragmatic trials exist in MS which rarely assess drugs. Despite the widely available routine data infrastructures, very few trials utilize them. There is an urgent need to leverage the potential of this pioneering study design to provide useful randomized real-world evidence.
Topics: Humans; United States; Multiple Sclerosis; Randomized Controlled Trials as Topic; Research Design; Patient Selection; United Kingdom
PubMed: 38253528
DOI: 10.1177/13524585231221938