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 Pharmaceutical companies, patient advocacy groups and lawmakers
around the world are pushing regulators to cut through what they see
as red tape and adopt more streamlined approval processes for new
drugs.
Europe has been looking at new approaches to drug testing for
several years and the issue came to the fore again in January after
U.S. President Donald Trump vowed to accelerate approvals to get new
drugs to patients faster.
However, critics of new approaches, such as lowering the
requirements for lengthy clinical trials, worry that selling drugs
with relatively little testing data, even if the go-ahead comes with
strict limits, will expose patients to greater risks.
The independent authority in Germany (IQWiG) that evaluates new
drugs and plays a key role in what price health services pay for
them has been one of the most vocal opponents of such new approaches
within Europe.
Given Germany is Europe's biggest drugs market and the fourth in the
world, its misgivings risk hurting a broader drive to bring new
treatments to patients faster, not least because drug companies may
conclude that dealing with price-setting authorities
country-by-country ends up being too costly.
"Accelerated approval on the basis of reduced data should be limited
to special situations. But there is reasonable concern that it is
intended to become the norm," said Stefan Lange, the deputy director
of Germany's Institute for Quality and Efficiency in Health Care (IQWiG).
The agency has in the past rejected pivotal studies that had
convinced the EMA to approve a drug, saying they were not
statistically valid. This has resulted in some drugs not getting
launched in Germany, or being withdrawn soon after their launch.
REAL-WORLD DATA
The push to adapt the approval process is partly the result of
advances in genetics that are yielding previously unknown treatments
for serious conditions and new tools that can forecast better which
patients can be helped, and which cannot.
Europe's drug licensing authority, the European Medicines Agency (EMA),
has been pursuing a new approach to testing known as "adaptive
pathways" for experimental drugs against serious, hard-to-treat
conditions. It picked six drugs under development for a pilot scheme
that ran from March 2014 to August 2016.
Two of the drugs were for rare cancers, two for hereditary blood
diseases, one for a fungal infection and one for heart problems. The
companies included U.S. biotech firm Bluebird Bio Inc <BLUE.O>,
Israel's Pluristem Therapeutics Inc <PSTI.O> and unlisted British
firms Immunocore Ltd and F2G Ltd.
One of the most contested methods advocated by the adaptive pathways
approach is to bring the launch of a promising drug forward on a
provisional basis, and then gather some of the evidence about its
effectiveness and side effects in an everyday medical setting, known
as the use of "real-world evidence".
Under established randomized controlled trials (RCT), new drugs are
given to some participants while a standard treatment or placebo is
given to a randomly assigned control group, with the results
determining whether the medicine gets approved.
Typically, neither group in the trial knows whether it is getting
the new treatment or not.
The new approach is to gather data from patients being treated,
using new medical sensors, smartphone apps and data processing
tools. Depending on the outcome of the real-world trial phase, the
group of patients eligible for the drug could be narrowed down or
widened for permanent approval.
This approach appeals to patient advocacy groups such as Eurordis
for rare diseases, or the European Cancer Patient Coalition, which
has called for more faith in real-world data and letting patients
decide whether they want to take the risk.
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"BOUND TO FAIL"
Germany's IQWiG argues that reducing the role of randomized trials
goes against the scientific principles that are needed to get clear
results on the risks and benefits of a new treatment.
IQWiG's Lange said relying on real-world evidence would mean
experimental research, with all its risks of side effects, would be
moving into the "uncontrolled environment" of everyday medical care
- and that could only be justified if the early signs of a drug's
therapeutic benefits were truly dramatic.
Linked to this is the problem that once a treatment gets even a
provisional green light, it would be hard to conduct a randomized
trial simply because it would be unethical to arbitrarily deny some
patients an approved treatment.
Attempts to preserve comparison benchmarks for real-world evidence
projects include drawing on data from patients still taking older
treatments elsewhere.
IQWiG argues that any factors playing a role in the composition of
study groups would skew the findings. "Any attempt to statistically
eliminate the distortions from these selection mechanisms afterwards
is bound to fail," said Lange.
France is another country to voice scepticism about the EMA's new
approach and some smaller countries have expressed misgivings
privately. France's Haute Autorite de Sante, for example, says it
has "mixed feelings" about expanding existing conditional marketing
approval rules, according to Chantal Belorgey, its director in
charge of medical assessment.
But Britain's National Institute for Health and Care Excellence
(NICE) said it supported the adaptive pathways concept and was
exploring how different sources of evidence could supplement data
from randomized trials.
The EMA's Senior Medical Officer Hans-Georg Eichler also says the
advent of precision drugs which would only be used by small groups
of patients has added urgency to the quest for new sources of
evidence to complement the established trial route.
Researchers are splitting medical conditions such as cancer or
neurodegenerative diseases into ever smaller sub-groups as they
learn to parse through the multitude of genetic traits that fuel a
disease. But that is leading to smaller drug trials, making it
difficult to produce statistically reliable results.
The EMA is now taking stock of the conflicting views about its pilot
scheme from the national cost-effectiveness watchdogs, patients and
organizations that pay for healthcare.
In the meantime, the companies involved in the pilot are continuing
to receive scientific advice from the EMA and the scheme is open to
new applicants, a spokeswoman said.
(Additional reporting by Matthias Blamont in Paris; editing by David
Clarke)
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