By Peter Loftus
Drugmakers are trying to win drug approvals by parsing vast data
sets of electronic medical records, shifting away from lengthy, and
costly, clinical trials in patients.
Pfizer Inc., Johnson & Johnson and Amgen Inc. are among the
drugmakers that have submitted the data-mining analyses to the U.S.
Food and Drug Administration in seeking approval to sell new
medicines or for new uses for older ones. The FDA has approved new
uses for breast cancer, bladder cancer and leukemia drugs in part
based on the data.
For the companies, the use of real-world data can cut costs and
shorten drug-development times. Instead of finding trial subjects,
companies simply mine hospital and doctor files for cases where
patients already took a drug in routine medical care, looking for
changes in blood pressure, tumor size and other readings to see if
the medicine is helping or causing a side effect.
This real-world evidence is sometimes used in lieu of a clinical
trial's control arm, to compare outcomes for past patients who got
a standard treatment against people who are taking a new drug in a
clinical trial. Such analyses can take months, compared with years
for prospective clinical trials.
Some doctors worry about forsaking clinical trials, which are
carefully designed and conducted in patients to get a sound read on
a drug's safety and efficacy. Health records often have errors, the
skeptics say, and even an analysis of records that are error-free
doesn't have the same scientific rigor as a clinical trial in
sizing up a drug.
Data from a clinical trial "are invaluable because it gives you
a sense of, 'In perfect circumstances, did the intervention work?'"
said Dr. Joseph Ross, professor of medicine and public health at
Yale School of Medicine.
Supporters of real-world analyses say it is unlikely they would
replace standard clinical trials needed for the initial approval of
a new drug. Instead, data-mining could augment such trials or be
done instead of trials for secondary approvals of a new use, when
patients are already taking the drug for an unapproved use and can
be tracked.
Clinical trials have been a bedrock of medical testing for
decades. The most reliable ones randomly assign some subjects to
take an experimental drug, while other subjects get a placebo or
older drug.
But for rare diseases especially, it can take awhile to even
enroll enough patients in studies. And their cost can limit the
number of trials that companies can fund, drugmakers say.
A 2016 law required the FDA to explore greater use of real-world
data, and the agency is developing standards to assess the
reliability of different data sources and which kinds of decisions
the data support.
"Real-world evidence should not be a means toward dropping
standards, but rather a mechanism to have more efficiency in
evidence generation while maintaining standards," said FDA
Principal Deputy Commissioner Amy Abernethy, a former executive at
health-data firm Flatiron Health.
A market has emerged in recent years for digital drug-use
information. Iqvia Inc., which tracks prescription and health data,
has about a dozen projects under way, said Nancy Dreyer, the
company's chief scientific officer of real-world evidence.
Swiss drugmaker Roche Holding AG has spent about $5 billion in
recent years acquiring two health-data companies: Flatiron provides
electronic health-record software to cancer clinics and analyzes
data from those records for drug companies, while Foundation
Medicine tests patients' tumor samples for genetic mutations and
aggregates the information for drug research.
Roche included a Flatiron analysis of patients whose cancer has
a certain genetic defect in the company's application to market a
new drug targeting that defect, Rozlytrek, which FDA approved in
August.
Amgen used real-world data from leukemia patients to serve as a
comparison for a small clinical trial in which all patients in the
trial received its leukemia drug Blincyto. The FDA last year used
the analysis in its decision to approve a new use for Blincyto
treating patients who are in remission but have some cancerous
cells that put them at risk for relapse.
Amgen would have had to enroll at least 50% more patients in the
clinical trial to have a standard control arm, said Elliott Levy,
Amgen's senior vice president of global development.
Such trials "typically involve the potential to be randomized to
existing standard of care or even no therapy, when what patients
want is the opportunity to be treated with a promising
experimental" drug, he said.
J&J used Flatiron and Foundation data to find that
bladder-cancer patients with a certain genetic trait didn't benefit
significantly from certain immune-boosting drugs. This analysis
augmented a separate clinical trial in which patients with the same
genetic trait did benefit from J&J's experimental drug
Balversa, said Craig Tendler, vice president of oncology clinical
development and global medical affairs at J&J.
J&J included the Flatiron/Foundation results in its
application for Balversa's approval, which the FDA granted in April
2019.
Pfizer's breast-cancer drug Ibrance was originally approved in
2015 for women based on a clinical trial. After some doctors began
prescribing the drug to men off label, Pfizer contracted with
Flatiron to mine electronic health records to see how men who got
the drug fared compared with those who hadn't.
Separately, Iqvia reviewed prescription claims and found male
breast-cancer patients stayed on Ibrance longer than those taking
other drugs.
Chris Boshoff, Pfizer's chief development officer for oncology,
said the analyses took less than a year and cost a fraction of a
clinical trial, which he estimated would have taken four or five
years and cost tens of millions of dollars.
But an FDA reviewer of Pfizer's application said the Flatiron
data provided limited evidence of Ibrance's effectiveness in men
because of small sample sizes, according to an FDA document
obtained by The Wall Street Journal via a public-records request.
And the two patient groups weren't well balanced on factors like
age, the FDA reviewer said.
FDA reviewers also said it was difficult to conclude from the
Iqvia analysis whether an increase in prescription duration
translated into improved survival or a delay in disease
progression.
Yet the FDA approved the use of Ibrance in men, noting that the
prior clinical trials in women gave the agency the confidence the
drug could help men, supported by the real-world evidence and
Pfizer's safety-tracking databases.
Write to Peter Loftus at peter.loftus@wsj.com
(END) Dow Jones Newswires
December 23, 2019 05:44 ET (10:44 GMT)
Copyright (c) 2019 Dow Jones & Company, Inc.
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