What is a Pragmatic Clinical Trial
Definition of a Pragmatic Clinical Trial
Karen Staman, MS
Jonathan McCall, MS
Liz Wing, MA
According to Califf and Sugarman, there are “three key attributes of PCTs: (1) an intent to inform decision-makers (patients, clinicians, administrators, and policy-makers), as opposed to elucidating a biological or social mechanism; (2) an intent to enroll a population relevant to the decision in practice and representative of the patients or populations and clinical settings for whom the decision is relevant; and (3) either an intent to (a) streamline procedures and data collection so that the trial can focus on adequate power for informing the clinical and policy decisions targeted by the trial or (b) measure a broad range of outcomes. Given these attributes, a common-sense definition for a PCT would thus be as follows:
Designed for the primary purpose of informing decision-makers regarding the comparative balance of benefits, burdens and risks of a biomedical or behavioral health intervention at the individual or population level” (Califf and Sugarman 2015).
To achieve generalizable results in an efficient manner, PCTs commonly take place in the setting where patients already receive their usual clinical care. In contrast with traditional RCTs, the intention is to avoid the need for a separately constructed infrastructure with specially trained research staff responsible for data collection. For a broader, more representative population, eligibility criteria are minimized and recruitment expanded to potentially all eligible individuals receiving care in the participating setting. Intervention delivery, participant follow-up, and adherence protocols are more flexible and closely align with usual care in order to understand the real-world implications of the intervention. Arguably, many of these pragmatic qualities occur along a spectrum, with some trials being more pragmatic than others (Thorpe et al. 2009).
There are many current examples of PCTs (see Table). The NIH Collaboratory supports the design and execution of Demonstration Projects, which are PCTs that address questions of major public health importance. As another example, the Patient-Centered Outcomes Research Institute (PCORI) funded the National Patient-Centered Clinical Research Network (PCORnet) to link multiple integrated health systems and ‘‘patient-powered’’ networks to conduct comparative effectiveness research and explore questions about conditions, care, and outcomes that matter most to patients and their families. PCORnet consists of clinical data research networks and patient-powered research networks that are linked through a distributed research network (DRN) to facilitate multi-site, observational, and interventional research (Fleurence et al. 2014). The DRN harnesses data from the electronic health record for research, allows each participating organization to maintain physical and operational control over their data, and minimizes the transfer of individual-level clinical data (Fleurence et al. 2014). PCORnet’s first PCT is ADAPTABLE: the Aspirin Study.
NIH Collaboratory Demonstration Projects
|Study Name ClinicalTrials.gov number
||Project Goal||Setting||Population||Unit of Randomization|
|PPACT Pain Program for Active Coping and Training (NCT02113592)||Help patients adopt self-management skills for chronic pain, limit use of opioid medications, and identify factors amenable to treatment in the primary care setting||Three staff model health plans||Patients with chronic pain on long-term opioid therapy (~800 patients)||Cluster-randomization by primary care provider|
|STOP CRC Strategies and Opportunities to Stop Colon Cancer in Priority Populations (NCT01742065)||Improve the rates of colorectal-cancer screening by mailing fecal immunochemical testing tests to patients at Federally Qualified Health Centers||26 Federally Qualified Health Center clinics||Individuals eligible for screening per the US Preventive Task Force guidelines (~41,000 patients)||Cluster randomization by Federally Qualified Health Center clinic|
|SPOT Suicide Prevention Outreach Trial (NCT02326883)||Compare outcomes in patients who receive care-management or online skills training for suicide prevention versus usual care||Three large health care systems||Individuals at elevated risk for suicide on a depression scale (~19,500 patients)||Individual randomization|
|TiME Time to Reduce Mortality in End-Stage Renal Disease (NCT02019225)||To determine whether increasing hemodialysis session durations reduces mortality and hospitalization rates for patients receiving maintenance hemodialysis care||266 dialysis facilities operated by two dialysis provider organizations.||Adults who have initiated treatment with maintenance hemodialysis within the past 120 days (~6,800 patients)||Cluster randomization by dialysis facility|
|PROVEN Pragmatic Trial of Video Education in Nursing Homes (NCT02612688)||Determine if showing advanced care planning videos in nursing homes affects the rates of hospitalization||360 nursing homes||2 nursing home health systems serving long-stay (>12 months) patients with advanced comorbid conditions (~15,000 patients)||Cluster randomization by nursing home|
|LIRE Lumbar Image Reporting with Epidemiology (NCT02015455)||Determine if inserting epidemiological benchmarks (essentially representing the normal range) into lumbar spine imaging reports reduces subsequent tests and treatments||4 health systems||100 clinics (~245,000 patients)||Cluster randomization by clinic; stepped-wedge, one-way crossover design|
|ABATE Active Bathing to Eliminate Infection (NCT02063867)||Determine if using antiseptic bathing for all patients and nasal ointments for patients harboring methicillin-resistant Staphylococcus aureus (MRSA) reduces multidrug-resistant organisms and bloodstream infections||53 hospitals||Patients in adult medical, surgical, oncology, and step-down units. (~600,000 patients)||Cluster randomization by hospital|
|ICD-Pieces Improving Chronic Disease management with Pieces (NCT02587936)||Improve care for patients with chronic kidney disease, diabetes, and hypertension by using a novel technology platform (Pieces) that uses the electronic health record to identify patients and by assigning practice facilitators within primary care practices or community medical homes||4 healthcare systems||Patients with multiple co-morbid conditions (chronic kidney disease, diabetes, and hypertension; ~11,000)||Stratified cluster randomization of clinical practices within health systems|
|TSOS Truama Survivors Outcomes and Support
|To coordinate care and improve outcomes for trauma survivors with post-traumatic stress disorder (PTSD) and comorbidity and to provide the American College of Surgeons with multisite pragmatic trial evidence that could further inform regulatory policy||25 US level 1 trauma centers||Trauma survivors with PTSD and comorbidity (~1000 patients)||Cluster randomization by trauma center; stepped-wedge design|
This table is based on a table previously published by the Colloboratory in a white paper titled Lessons Learned from the NIH Health Care Systems Research Collaboratory Demonstration Projects and is used with permission (NIH Collaboratory Healthcare Systems Interactions Core 2016).
Califf RM, Sugarman J. 2015. Exploring the ethical and regulatory issues in pragmatic clinical trials. Clin Trials. 12:436–441. doi:10.1177/1740774515598334.
Fleurence RL, Curtis LH, Califf RM, Platt R, Selby JV, Brown JS. 2014. Launching PCORnet, a national patient-centered clinical research network. J Am Med Inform Assoc. 21:578–582. doi:10.1136/amiajnl-2014-002747.
Thorpe KE, Zwarenstein M, Oxman AD, et al. 2009. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 62:464–475. doi:10.1016/j.jclinepi.2008.12.011. PMID: 19348971.