Study replicates pivotal trial results using ‘real world evidence’

A study published in JAMA Internal Medicine on Monday was able to replicate the results of a large randomized controlled clinical trial for the blood pressure drug telmisartan using so-called real world evidence gathered from insurance claims data.

The goal of the study, which was conducted by researchers at Harvard Medical School, was to investigate whether health care databases can be used to confirm findings from clinical trials conducted to support additional indications for already approved drugs.

In recent years, the FDA has stepped up its efforts to advance the use of data gathered from “real world” sources, such as insurance claims data, electronic health records, and patient registries in its decision making.

Historically, FDA’s use of real world evidence has focused on identifying and assessing safety issues for marketed products, but recently leaders at the agency have suggested real world evidence (RWE) could be used to support new indications or label expansions for drugs, and in June the agency expanded the use of Edwards Lifesciences’ Sapien 3 transcatheter aortic valve based on data gathered from a patient registry.


To conduct the study the authors looked at anonymized insurance claims data for some 64,000 patients that were available before the supplemental indication for telmisartan was approved for patients newly prescribed either telmisartan or ramipril, another drug used to treat high blood pressure.

The pivotal study, known as Ongoing Telmisartan Alone and in Combination with Ramipril Global End-point Trial (ONTARGET), was conducted to determine whether telmisartan is noninferior to ramipril in preventing cardiovascular events and to see whether the combination of the two drugs is superior to ramipril alone.

“Among patients newly prescribed telmisartan and ramipril before the FDA’s decision to approve a supplemental indication for telmisartan, we found results that were almost identical to those of the randomized clinical trial that led to telmisartan’s supplemental indication,” the authors write.

The authors say the study shows promise as a way to reduce the amount of time and money spent to support supplemental indications for some drugs. While ONTARGET took seven years to complete and cost tens of millions of dollars, the authors say their study was completed in just 12 weeks and at a hundredth of the cost.

But while the authors were able to confirm the results of ONTARGET with their cohort study, they note that doing so for supplemental indications for most drugs would not be feasible.

From 2005-2014 the authors identified 138 new indications for drugs approved by FDA, more than three-quarters (78%) of which were granted based on a primary outcome that would not be identifiable in existing healthcare databases, such as pathology results or changes in clinical scores.

“The fact that our case study bolstered the conclusions of a trial designed to identify a supplemental indication for a marketed medication and was done relatively efficiently using available data sets, rigorous epidemiologic methods, and modern software platforms supports the concept of conducting similar database analyses as part of routine practice for manufacturers submitting applications for supplemental indications to the FDA,” the authors write, noting that FDA could facilitate the use of such studies by providing guidance on they are appropriate.

First published here. Regulatory Focus is the flagship online publication of the Regulatory Affairs Professionals Society (RAPS), the largest global organization of and for those involved with the regulation of healthcare and related products, including medical devices, pharmaceuticals, biologics and nutritional products. Email news@raps.org for more information.

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
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Atlas Venture Cambridge, MA

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