Transcript Study Development and Design

Study Development and Design
Suzanne Adams RN MPH
Director, Clinical Operations
Jefferson Clinical Research Institute
Study Design: Learning Objectives
Participants will be able to:
1. Describe types /characteristics of clinical research studies
2. Identify the 4 phases of clinical trial
3. Demonstrate understanding of study design factors
Study Design: Types and Characteristics
• Observational
• Registry
• Interventional
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Prospective
Retrospective
Cross-sectional
Cohort
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Randomized Controlled (RCCT)
Quasi-Experimental (no randomization)
Crossover/Stratified
Blinding / Double Blind
• Single Site or Multi-Center
• RCC with Enrolling Sites
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Adaptive/Pragmatic Design
Patient-Centered/Patient Reported Outcomes
Comparative Effectiveness
Big Data, Computational Analyses
Study Design: Industry vs. Academic Sponsor
Industry clinical research processes can be long and expensive.
• Investment over $1 billion (15.2 m phase I / $41.7 m phase II / $115.2 m in phase III
• 10-15 years for a compound or device to advance from benchtop to bedside
• Subjects may be assigned to take one or a combination of:
 Investigational drugs
 Approved drugs
 Placebo* (*Standard Care)
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Sponsor manages registering and reporting / Clinicaltrials.gov, IND to FDA
Academic Research
• Intramural funding / Support for pilot studies – informing larger grant development
• Resources and sharing
• Value of Academic Capital
• NIH Clinical and Translational Science Awards
• Requirements for Reporting Results - Clinicaltrials.gov
Study Design: Drug Development Phases
Study Design: Phase I and II
Phase I
• Test investigational drug for the first time in humans
• Small number of healthy volunteers
• Evaluate safety - Determine safe dosage range - Identify adverse effects.
NOTE: Due to toxicity of the agent, cancer trials may do Phase I studies on subjects with
advanced disease who have not responded to SOC treatment
Phase II
• Investigational drug given to a larger number of people
• People have a particular disease or condition
• Determine effectiveness - Further evaluate safety
IIa Pilot clinical trials may focus on dose-response, type of patient, frequency of
dosing, or numerous other characteristics of safety and efficacy
IIb Well controlled trials representing the most rigorous demonstration of efficacy
Sometimes referred to as pivotal trials
Clinical Trial Design: Phase III and IV
Phase III
• Several hundred to several thousand people
• Participants have the appropriate disease or condition
• Additional testing for safety, effectiveness, side effects, comparative effectiveness
IIIa Trials conducted after efficacy of the medicine is demonstrated, but prior to
regulatory submission of a New Drug Application (NDA)
Also conducted in special groups or under special conditions dictated by the nature
of the medicine and disease. Provide information for package insert and labeling
IIIb Clinical trials conducted after regulatory submission of an NDA or other dossier,
but prior to the medicine's approval and launch. These trials may supplement
earlier trials, complete earlier trials, or may be directed toward new types of
trials (e.g., quality of life, marketing)
Phase IV
• After a drug is available by prescription, FDA requires reporting of additional
information to assess longer-term risks, benefits and use
• Post-marketing Surveillance or Pharmacovigilance
Study Design: Elements
• Research Question based on Scientific Background and Rationale
• Hypothesis / Null Hypothesis
• Objectives / Endpoints selected to support the study's hypotheses
• Sample Size / Power sample calculation
• Validity – Internal, External, Construct
• Data Collection and Analyses– Descriptive, Correlation, Inferential
• Intervention Design and Risk Evaluation
• Randomization to avoid Selection Bias or Probability sampling
• Blinding to avoid Observation Bias
Industry vs. Federal Grants vs. Investigator-Initiated
CONSIDERATIONS
• Funding Source (Commercial, Federal, Foundation)
• Duration of Study
• Size and Scope
• Conflicting or Competing Studies
• Specific Aims/Exploratory Aims
• Endpoints and Outcomes
• Investigator Role/Expectations
• FDA Interactions for IND/IDE / Exemption “Waiver”
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Contract Research Organizations
Trial Networks
DSMB/DSMP
Enrollment Goals and Timelines/Milestones
Data Quality Monitoring
Study Design: Elements of Operational Analysis
• Tools for Pre-Screening and Screening
• Equipment: Acquisition and Care (Maintenance)
• Coordinator Training
• Standard of Care Overlap
• Subject Injury Language
• Investigational Product/Device Control
• Management/Cooperation/Resources needed for required labs or tests
• Safety Assessments
• Subject Retention
• Clean Data / Data Query Resolution
• Analysis Responsibilities
Clinical Research: Non-Clinical Site Fees
2011 -2015: Median non-clinical U.S. site fee/subject increased from $4,000 to $6,500.
“Non-clinical site fees” include visit, start-up, IRB, pharmacy, administrative and other
fees, except charges for procedures and tests with CPT codes, or scale assessments.
Questions and Comments
Thank You !