1. Clinical Trial Technologies for Precision Medicine: The Current State of the Art
Steven Schwager, Medidata Solutions & Cornell University
Ruthie Davi, Medidata Solutions
Therese Dolan, Medidata Solutions
Jeff Wiser, Medidata Solutions
Joint Statistical Meetings July 29, 2018

2. Outline The nature of precision medicine
FDA initiatives encouraging development of targeted therapies
Importance of the revolution in genomics for precision medicine
The 5 Vs of big data & pivotal role of big data in precision medicine
4 clinical trial technologies with essential capabilities for precision medicine
(1) Continuous collection & integration of data from myriad sources
(2) Adaptive & iterative study design & execution
(3) Maintenance & management of data throughout the study life cycle
(4) Advanced analytics for research discovery
Optional footer

3. Outline (cont) The great potential of precision medicine for:
Developing exploratory hypotheses ← Technologies (1) & (2)
Evaluating these hypotheses ← Technologies (3) & (4)
Producing safer, more effective treatments for patient subgroups determined by favorable benefit-risk profiles – more accurate predictive models for different subsets of patients
Complexities of precision medicine study designs require substantial planning, investment, & commitment from all stakeholders
Goal of this talk: Describe the current state of clinical trial technologies that enable developing precision medicine trials that maximize chances of success.
Optional footer

4. Introduction
Precision medicine (National Academy of Science): “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person”
Additional individual characteristics: anatomical, physiological
Rapidly developing alternative to traditional “one-size-fits-all” medical practices: use best course of prevention / treatment for general population; if initial treatment fails, use next standard treatment, again for population
Clinicians, patients, & drug regulators are adapting to rapidly expanding access to wide range of data
Potential to improve patient care, optimal outcomes, & understanding of disease etiology
Optional footer

5. Precision Medicine and the FDA
Woodcock (Director, CDER) & LaVange (Director, Office of Biostatistics), NEJM 2017: need to capitalize on similarities among trials (e.g., shared control group and recruiting) to gain efficiencies in drug development, using umbrella, basket, & platform trials (e.g., I-SPY2, Lung-Map)
FDA’s Precision Medicine Initiative, 2016: to facilitate identification of genetic drivers of disease & develop better diagnostic tools & treatments
FDA’s precisionFDA portal for oversight, analysis, & validation of NGS (next-generation sequencing) / high-throughput sequencing methodology
FDA’s approval of growing # of medicines for defined subsets of patients, including Keytruda to treat patients whose cancers have specific biomarker
FDA’s approval of drugs & companion diagnostics to identify best patients
Optional footer

6. Genomic Data & Current State of Precision Medicine
Revolutionary advances in genomics are improving understanding of human biology & disease and opportunities for precision medicine (PM)
Example: breast cancer, single disease → distinct molecular subtypes with biomarkers that have been translated into targeted clinical practice
PM evolving from specialized approach to part of standard clinical practice
In Sept 2017, search for “precision medicine” on clinicaltrials.gov returned ≈180 studies, & many more studies involving PM are not explicitly labeled
Keywords related to biomarkers & NGS → # is > by ≈ order of magnitude
Training clinicians to understand PM & use it effectively is important
Establishing suitable infrastructure / platform is crucial → (next slide)
Optional footer

7. Genomic Data & Current State of Precision Med (cont)
To predict outcomes accurately in a patient outcome, Precision Medicine requires massive amounts of data, often from disparate streams, some generated continuously
Clinical development platform for PM must – in real time:
seamlessly ingest, aggregate, integrate, & analyze these datasets in easy-to-use workflow that helps discover meaningful relationships resulting in improved patient outcomes
adapt to emerging data and enable redefining patient clusters into more precise subsets and redesigning study designs for refined hypothesis testing
enable conceiving, executing, & interpreting suitable analyses
Optional footer

8. Big Data & the Path to Precision Medicine
Clustering patients into increasingly more precise subsets requires measuring patients on numerous attributes of many different types
Platform must be flexible, integrated, & intelligent to accomplish the tasks on last slide, which are formidable because of the 5 Vs of big data:
Volume (Ex: over 3 billion nucleotides in human genome)
Velocity (Ex: sensor, imaging data containing hundreds of pts/sec)
Variety (Ex: lab tests, genomic sequencing, sensor readings, imaging)
Veracity (Ex: missing & inaccurate observations must be minimized)
Value (Ex: analytical algorithms must yield improved performance)
Optional footer

9. Clinical Trial Technologies for Precision Medicine
Adaptable platform must leverage both historical and in-study datasets to update and optimize models, revise cohort selection, risk stratification, & consequent intervention assignment
Advanced analytics must enable revising treatment models as new information arrives
Platform must provide these capabilities:
Continuous collection, aggregation, & integration of many data sources
Adaptive & iterative study design and execution as new info arrives
Maintenance & management of data throughout study life cycle
Advanced analytics for research discovery during study & post-study
Optional footer

10. Key Tasks in Designing a Precision Medicine Study
Generate the protocol: establish solid scientific foundation for predictive precision medicine trial
Plan adequately for complex trial designs and real-time decision-making, including criteria for decisions to modify & discontinue treatments
Plan to measure & ingest wide array of relevant data types and attributes
Construct platform to handle data flow & quality, trial logistics, & real-time data analysis & trial redesign
Evaluate innovative methods for analysis and interpretation of results
After finalizing study objectives & outcomes, consider incorporating specialized designs, including: adaptive trials, longitudinal cohort studies, basket trials, umbrella trials, N-of-1 studies
Optional footer

11. Conclusions
Advanced clinical trial technologies are crucial for precision medicine trials
As the range of data streams increases, the promise is that precision medicines will become increasingly targeted
A platform that has the capabilities we discussed is crucial for precision medicine trials
The complexities of the precision medicine approach require solid planning, investment, and commitment from all stakeholders
Precision medicine has unique potential for discovering highly effective targeted treatments
For greater detail and references, see
Davi, Dolan, Wiser, & Schwager, Journal of Precision Medicine, Dec 2017
Optional footer