Developing approaches to accelerate clinical trials using real world data (RWD) from electronic health records (EHR)

Lead Investigator: Brian Gillette, Droice Labs
Title of Proposal Research: Developing approaches to accelerate clinical trials using real world data (RWD) from electronic health records (EHR)
Vivli Data Request: 10155
Funding Source: None
Potential Conflicts of Interest: Brian Gillette is an employee and shareholder of Droice Labs, a for-profit organization. This position could be perceived as a potential conflict of interest that may influence the planning, conduct, interpretation, and outcomes of the proposed research. To mitigate this, he commits to full disclosure of this affiliation in all publications and presentations, adherence to independent oversight and data audit protocols, and the objective reporting of all findings.

Mayur Saxena is an employee and shareholder of Droice Labs, a for-profit organization. This position could be perceived as a potential conflict of interest that may influence the planning, conduct, interpretation, and outcomes of the proposed research. To mitigate this, he commits to full disclosure of this affiliation in all publications and presentations, adherence to independent oversight and data audit protocols, and the objective reporting of all findings.

Tasha Nagamine is an employee and shareholder of Droice Labs, a for-profit organization. This position could be perceived as a potential conflict of interest that may influence the planning, conduct, interpretation, and outcomes of the proposed research. To mitigate this, she commits to full disclosure of this affiliation in all publications and presentations, adherence to independent oversight and data audit protocols, and the objective reporting of all findings.

Summary of the Proposed Research:

Randomized controlled trials (RCTs) are the standard for generating evidence on new treatments but are costly and time-consuming. If real-world data (RWD) from electronic health records (EHR) could be used to help understand the safety and efficacy of new treatments, it would reduce the need for placebo controls in RCTs, speeding up trials and bringing therapies to patients sooner, thereby enhancing patient care.

RWD can be used in RCTs in a number of ways. For example, RWD external control arms (ECAs), control groups created from data outside the trial, can be used when randomization is not ethical or feasible. Hybrid controlled trials combine clinical trial data with external data to bolster the control group, and can be used for common conditions for which the Food and Drug Administration (FDA) requires RCTs. Predictive models based on RWD can increase the ability to detect the effects of treatments, reducing the number of required participants.

However, there are major challenges in using EHR data in clinical trials. EHR data, originally compiled for financial and operational purposes, must undergo complex processing to ensure it is ready for analysis and to ensure accuracy and reliability for research. Data errors can create biases that compromise the validity of findings. The FDA has been rejecting submissions using RWD because data reliability – accuracy, completeness, and traceability. For RWD to be reliable, traceability to raw data is required to quantify data accuracy.
Droice Labs developed SuperLineage, an RWD traceability solution specifically designed to solve this challenge. SuperLineage is used to both find and fix data processing errors to improve RWD quality and to measure data accuracy. Droice Labs’ discussed SuperLineage with the FDA, where both FDA and Droice agreed that accuracy, completeness, and traceability are necessary for regulatory use of RWD. Furthermore, Droice and Clinical Data Interchange Standards Consortium (CDISC), the body responsible for developing regulatory data submission standards for FDA, are building an RWD lineage metadata standard based on SuperLineage for FDA regulatory submissions

In this project, Droice Labs is validating RWD by matching patient-level data from multiple RCTs with cohorts from its US hospital partners. SuperLineage will be used by the research team to validate the data by measuring the accuracy and completeness of RWD variables. For each selected RCT, the primary analysis will be replicated across the RCT and RWD study arms to evaluate whether the conclusions of the RCT are reproducible in the RWD with and without considering the error bounds measured using SuperLineage. This research will add to medical science by developing methods to reduce the number of participants required in clinical trials through the use of RWD, which can ultimately improve patient care by speeding up the development of new therapies.

Requested Studies:

A Randomized, Parallel-Arm, Double-Blinded Study Comparing the Effect of Once-Weekly Dulaglutide With Placebo in Patients With Type 2 Diabetes Mellitus on Sulfonylurea Therapy (AWARD-8: Assessment of Weekly AdministRation of LY2189265 in Diabetes – 8)
Data Contributor: Lilly
Study ID: NCT01769378
Sponsor ID: 13193

The Impact of LY2189265 Versus Metformin on Glycemic Control in Early Type 2 Diabetes Mellitus (AWARD-3: Assessment of Weekly AdministRation of LY2189265 in Diabetes-3)
Data Contributor: Lilly
Study ID: NCT01126580
Sponsor ID: 11375

A Randomized, Open-Label, Parallel-Arm Study Comparing the Effect of Once-Weekly Dulaglutide With Once-Daily Liraglutide in Patients With Type 2 Diabetes (AWARD-6: Assessment of Weekly AdministRation of LY2189265 in Diabetes-6)
Data Contributor: Lilly
Study ID: NCT01624259
Sponsor ID: 11377

A Randomized, Parallel-Arm, Double-Blind Study of Efficacy and Safety of Dulaglutide When Added to SGLT2 Inhibitors in Patients With Type 2 Diabetes Mellitus
Data Contributor: Lilly
Study ID: NCT02597049
Sponsor ID: 15361

A Phase 2/3, Placebo-Controlled, Efficacy and Safety Study of Once-Weekly, Subcutaneous LY2189265 Compared to Sitagliptin in Patients With Type 2 Diabetes Mellitus on Metformin
Data Contributor: Lilly
Study ID: NCT00734474
Sponsor ID: 11422

A Randomized, Double-Blind Trial Comparing the Effect of Dulaglutide 1.5 mg With Placebo on Glycemic Control in Patients With Type 2 Diabetes on Basal Insulin Glargine
Data Contributor: Lilly
Study ID: NCT02152371
Sponsor ID: 13195

A Randomized, Placebo-Controlled Comparison of the Effects of Two Doses of LY2189265 or Exenatide on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Pioglitazone (AWARD-1: Assessment of Weekly Administration of LY2189265 in Diabetes-1)
Data Contributor: Lilly
Study ID: NCT01064687
Sponsor ID: 11373

A Randomized, Open-Label, Parallel-Arm Study Comparing the Effect of Once-weekly Dulaglutide With Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes and Moderate or Severe Chronic Kidney Disease
Data Contributor: Lilly
Study ID: NCT01621178
Sponsor ID: 13798

A Randomized, Phase 3, Open-Label Trial Comparing the Effect of LY3298176 Versus Titrated Insulin Degludec on Glycemic Control in Patients With Type 2 Diabetes
Data Contributor: Lilly
Study ID: NCT03882970
Sponsor ID: 16997

A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients With Type 2 Diabetes
Data Contributor: Lilly
Study ID: NCT03987919
Sponsor ID: 17001

A Multicenter, Double-Blind Study to Determine the Efficacy and Safety of SYR-322 Plus Pioglitazone HCl (Actos®), SYR-322 Alone or Pioglitazone HCl Alone in Subjects With Type 2 Diabetes
Data Contributor: Takeda
Study ID: NCT00395512
Sponsor ID: 01-06-TL-322OPI-002