Point of Care Clinical Trials Building a Learning Healthcare System Louis Fiore louis.fiore@va.gov
Evidence Creation Randomized Controlled Trials Gold standard Resource intense Observational studies Affordable Bigger n s Contend with bias
POC Clinical Trial - Definition A clinical trial with a substantial portion of its operations conducted by clinical staff in the course of providing patient/subject s routine clinical care and where the choice of treatment is between two equivalent options
POC Trials - Attributes Clinical research performed with minimal perturbation of the clinical care ecosystem Subject identification and randomization occurs at usual health care encounter Minimal study-defined procedures or visits (mostly directed via EMR) Outcome data captured passively
POC Trial - Advantages Pragmatic qualities address issues of Clinical Effectiveness Results directly relevant to healthcare system ( locally selfish research ) Ability to assess long-term clinically relevant outcomes (lower cost) Faster (immediate) Integration of results into practice thereby lowering the T2 translation barrier Enhanced acceptance by providers Adaptive randomization Conversion to a decision support node Improved logistics: Facilitation of economic analysis Accommodates device and strategy studies
POC Requirements: Trial Design Limited to questions of the type: which approved treatment works better? Interventions with well described toxicity Broad inclusion criteria; limited exclusion criteria Objectively identifiable endpoints Minimal need for study specific visits
POC Requirements: Implementation Buy-in by providers and clinical operations Rational Approach to Regulatory Oversight Informed consent Engagement in research SAE reporting Ability to adapt the EMR (VistA) Scalable methodologies to support a national deployment
POC Trials Will Not: Explain how biological, etiologic, or behavioral mechanisms interact to produce the observed clinical outcomes Test new therapies where side effects are not well established
POC-CT Pilot Study Goals A pilot study was adapted to assess the following: 1. Ability to modify the of EMR (VistA) to conduct the research 2. Physician and patient acceptance 3. IRB and regulatory acceptance of approach 4. Identification of logistical obstacles
POCR Pilot Study Background: Best regimen for insulin administration (weight based versus sliding scale) in hospitalized patients is uncertain. No published data comparing outcomes Study Design: Open label randomized clinical trial comparing the two regimens in non-icu hospitalized diabetic patients in VA VISN 1, starting in Boston. Endpoints: Primary - length of hospital stay Secondary - inpatient glycemic control and readmission within 30 days for glycemic control
Recruitment Workflow
View of the Endocrine Medication Menu in VistA: Consider Patient for Study Enrollment Select Option 1
Study Information Page Study Information and Instructions (select Yes or No)
Enrollment Note Entry Dialog template for note (decision to enroll)
POC Desired State The final product of the initiative is to create a learning healthcare system through clinical effectiveness research that capitalizes on the national electronic medical record in a population that is pre-enrolled from the general population of the VA.
Moving from Current to Desired State Early introduction of Point of Care Research to regulatory/oversight thought leaders to plan the way forward Consider implementation requirements - from single site with highly engaged research personnel using in-person informed consent to national rollout Conduct focus groups of providers and patients to better understand acceptability Move toward blanket opt in for general enrollment into the program (non-study specific)
Requirements For POC Adoption Rethink relationship between clinical care and research Revisit engagement in research, consent, adverse event reporting Educate to create a cultural change in responsibilities of patients Reengineer the EMR infrastructure To allow questions to be asked and answered To facilitate decision-support adoption Develop novel analytical approaches New ideas for supporting research Alternative to the investigator-initiated approach Support of research by clinical care dollars
POC Milestones and Objectives FY 2011 FY 2012 FY 2013 Conduct proof of concept with Pilot Project Test application at other sites Develop and conduct education of stakeholders Write scholarly articles on concept and methodologies Begin discussions with OIT to consider enhancements to EMR/VistA for national implementation Complete and publish results of Pilot Project. Define use cases and identify proposals in which the POC methodology could be implemented Establish program parameters. Evaluate POCR technologies and methods Continue discussions with OIT and ORD Begin national education and training Implementation of use cases across a variety of VA sites (50+). Evaluate engagement in research; ethics. Refinement and tracking of metrics of success.
Closing Thoughts Here s a poke in the eye: CER is not scientific research, it is engineering Closing implementation gap is different from getting a generalizable result The science is in CER methods, not in the results but, the main value is in the results - as they are implemented! This suggests that stopping rules could be local to a site or system New sites could decide to borrow strength, or ride coattails of previous site experiences
The Bad News The health care system is inhospitable to intolerant of and unmoved by experimental research
The Good News The health care system is unaffordable unsuccessful, and on the verge of collapse.
POC-CT Research Team Principal Investigators: Louis Fiore and Philip Lavori Informatics: Leonard D Avolio and Chester Conrad CPRS Engineers: Gus O Neil and Tom Sabin Co-Investigators: Mary Brophy, James Kaufman, Mike Gaziano and Matt Liang Ethics and Informed Consent: John Hermos Content Expert: Stephen Swartz Data Management: Elizabeth Lawler, Ryan Ferguson and Galena Sokolovskaya Statisticians: Philip Lavori, Robert Lew and Gheorghe Doros
Sponsored by the VA Cooperative Studies Program Office of Research & Development Department of Veteran s Affairs Additional NIH support to Stanford University is gratefully acknowledged CTSA UL1 RR025744 CCSG P30 CA124435