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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 -
Trials Nov 2021Due to ongoing political and social conflicts, the number of international refugees has been increasing. Refugees are exposed to severe mental and physical strain, as...
Effects of an exercise and sport intervention among refugees living in a Greek refugee camp on mental health, physical fitness and cardiovascular risk markers: study protocol for the SALEEM pragmatic randomized controlled trial.
BACKGROUND
Due to ongoing political and social conflicts, the number of international refugees has been increasing. Refugees are exposed to severe mental and physical strain, as well as traumatic experiences during their flight. Therefore, the risk of psychiatric disorders is markedly increased among international refugees. International organizations have criticized the lack of early interventions as a key problem, because untreated mental disorders are often difficult to cure at a later stage. Today, exercise and sport have been successfully employed to treat a wide range of psychiatric disorders. With patients with post-traumatic stress disorders (PTSD), very limited empirical evidence exists, and studies carried out with international refugees are nearly non-existent.
METHODS
We intend to implement a pragmatic randomized controlled trial (RCT) with an exercise and sport intervention group (n = 68, 50% women) and a wait-list control group (n = 68, 50% women) in the Koutsochero refugee camp, located close to the city of Larissa (Greece). During the RCT, exercise and sport will be offered five times per week (60 min/session) for 10 weeks. Participants will be asked to participate in at least two sessions per week. The programme is developed according to the participants' needs and preferences and they will be able to choose between a range of activities. PTSD symptoms will serve as primary outcome, and several secondary outcomes will be assessed. Qualitative data collection methods will be used to gain a more in-depth appraisal of the participants' perception of the intervention programme. In the second year of study, the programme will be opened to all camp residents. A strategy will be developed how the programme can be continued after the end of the funding period, and how the programme can be scaled up beyond the borders of the Koutsochero camp.
DISCUSSION
By moving towards the primary prevention of chronic physical conditions and psychiatric disorders, a relevant contribution can be done to enhance the quality and quantity of life of refugee camp residents in Greece. Our findings may also strengthen the evidence for exercise as medicine as a holistic care option in refugee camps, by helping camp residents to adopt and maintain a physically active lifestyle.
TRIAL REGISTRATION
The study was registered prospectively on the 8 February 2021 with ISRCTN https://www.isrctn.com/ISRCTN16291983.
Topics: Female; Greece; Heart Disease Risk Factors; Humans; Male; Mental Health; Physical Fitness; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Refugee Camps; Refugees; Stress Disorders, Post-Traumatic
PubMed: 34802451
DOI: 10.1186/s13063-021-05808-2 -
Respiratory Research Mar 2020Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and...
Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial.
Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120.
Topics: Anti-Infective Agents; Humans; Idiopathic Pulmonary Fibrosis; Multicenter Studies as Topic; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 32164673
DOI: 10.1186/s12931-020-1326-1 -
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 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 -
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 -
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 -
Contemporary Clinical Trials Jul 2019Current guidelines recommend behavioral intervention to achieve a modest weight loss (e.g., 3-5%) as a first-line obesity treatment. Online behavioral obesity treatment,...
BACKGROUND
Current guidelines recommend behavioral intervention to achieve a modest weight loss (e.g., 3-5%) as a first-line obesity treatment. Online behavioral obesity treatment, delivered via the Rx Weight Loss (RxWL) program, produces clinically significant initial weight losses. However, the program's pragmatic utility in routine medical care has yet to be tested. Further, additional research is needed to determine how best to extend the RxWL program to facilitate weight loss maintenance. This paper summarizes methods for a pragmatic trial aimed at identifying optimal methods for implementation of RxWL in primary care and evaluating relative effectiveness of two approaches to weight loss maintenance.
STUDY DESIGN
RxWL will be implemented in a network of approximately 60 primary care clinics. Implementation outcomes (program uptake and completion metrics) will be compared between a Basic Implementation Intervention consisting primarily of access to RxWL, and an Enhanced Implementation Intervention with additional training in strategies for motivating and supporting patients in their use of RxWL and online clinician support tools for tracking patient progress. Second, two intervention approaches (Monthly Lessons versus Refresher Courses) within the RxWL patient platform will be tested against an educational control condition, and effects on 1-year weight loss maintenance will be compared.
CONCLUSION
This study will provide essential information about the feasibility and utility of online obesity treatment in primary care. It will provide novel information on two approaches to weight loss maintenance for patients in this setting. This project fills key gaps in evidence regarding best practices for obesity treatment in primary care.
Topics: Adolescent; Adult; Aged; Behavior Therapy; Female; Humans; Male; Middle Aged; Obesity; Pragmatic Clinical Trials as Topic; Primary Health Care; Randomized Controlled Trials as Topic; Therapy, Computer-Assisted; Treatment Outcome; Weight Reduction Programs; Young Adult
PubMed: 31063870
DOI: 10.1016/j.cct.2019.05.003