[Ip-health] Reuters - New Drugs Are Barely An Improvement Over Decades-Old Standbys, Study Finds

Riaz K Tayob riaz.tayob at gmail.com
Mon Jun 3 22:44:42 PDT 2013

[With the rise of the financial rentiers in the US, perhaps this sheds 
some light on the IPR rentiers...]

  New Drugs Are Barely An Improvement Over Decades-Old Standbys, Study

*Reuters*  | Posted: 06/03/2013 4:00 pm EDT


By Sharon Begley

NEW YORK, June 3 (Reuters) - Despite the more than $50 billion that U.S. 
pharmaceutical companies have spent every year since the mid-2000s to 
discover new medications, drugmakers have barely improved on old 
standbys developed decades ago.

Research published on Monday showed that the effectiveness of new drugs, 
as measured by comparing the response of patients on those treatments to 
those taking a placebo, has plummeted since the 1970s.

While that is already unwelcome news to drug and biotech companies, the 
consequences for the pharmaceutical industry could get worse under 
President Barack Obama's healthcare law.

The law established an independent research institute to compare the 
effectiveness of different treatments for the same condition. That way, 
patients as well as private insurers and government programs such as 
Medicare can stop paying for less effective therapies. If the new 
analysis is correct, then "comparative effectiveness research" could 
conclude that older drugs, which are more likely to be generics, are 
better than pricey new brand names that deliver the most profits for 

Fears of a crisis in drug innovation have grown over the years. When the 
healthcare journal Prescrire in 2011 ranked new drugs, only 17 of the 
984 developed since 2001 were deemed "a real advance" or better. And a 
survey of 184 expert physicians in 15 specialties published last month 
in Nature Reviews Drug Discovery showed the doctors were more likely to 
rate drugs more than a decade old as "transformative."

To be sure, drugs that completely change outcomes for patients continue 
to emerge. Gleevec, from Novartis, greatly extends life for leukemia 
patients, for instance. New antivirals such as Incivek from Vertex 
Pharmaceuticals have doubled the cure rate in hepatitis C, and Eylea 
from Regeneron Pharmaceuticals is better than anything previously 
developed for macular degeneration.

Because of those and other examples, "we believe that a lot continues to 
be accomplished in terms of yielding very, very positive results for 
patients, so there seems to be a disconnect between that and this 
paper," said Randy Burkholder, deputy vice president of policy at the 
Pharmaceutical Research and Manufacturers of America (PhRMA) trade group.


The new study in the journal Health Affairs examined 315 clinical trials 
that compared a drug to a placebo and were published in four of the 
world's top medical journals (BMJ, Journal of the American Medical 
Association, Lancet and New England Journal of Medicine) from 1966 to 
2010. The drugs targeted the full range of human ills, from 
cardiovascular disease and infections to cancer, mental disorders and 
respiratory illness.

In the early years, drugs easily beat the placebo: They were, on 
average, 4.5 times as effective, where effectiveness means how well they 
lowered blood pressure, vanquished tumors, lifted depression or did 
whatever else they were intended to.

But the trend line was inexorably downhill, found Dr Mark Olfson of 
Columbia University and statistician Steven Marcus of the University of 
Pennsylvania. By the 1980s drugs were less than four times better; by 
the 1990s, twice as good, and by the 2000s just 36 percent better than a 
placebo. Since older drugs were much superior to placebo and newer ones 
only slightly so, that means older drugs were generally more effective 
than newer ones.

"Their results are pretty compelling," said Dr Aaron Kesselheim of 
Harvard Medical School, who helped conduct the survey of physicians on 
"transformative" drugs but was not involved in this study. "It does 
appear that things are headed in the same direction, with newer drugs 
having relatively less efficacy."

Experts disagree on why that should be, but suspicions range from the 
U.S. regulatory process to basic biology.

"It may be that the drug discoveries based on low-hanging fruit were 
made long ago," said Olfson, as with discoveries based on the most basic 
or easily targeted causes of high blood pressure. In that case, older 
drugs based on those targets would pack a bigger punch than newer ones 
that target less-central causes of disease.

Or, it could be that the patients who volunteer for clinical trials have 
gotten harder to treat. In many cases, people volunteer because existing 
drugs are not helping their cancer, schizophrenia or other condition, 
Olfson said, "and may have forms of the disease where it's harder for a 
drug to demonstrate a benefit."

Another explanation could be that the scientific quality of clinical 
trials has improved over the decades, as the Health Affairs analysis 
found. Human studies in the 2000s were more likely than those in the 
1960s to enroll hundreds of patients rather than dozens.

"It may be that the compounds aren't getting less effective but that 
they're getting looked at more carefully," said Dr Harold Sox of the 
Dartmouth Institute for Health Policy and Clinical Practice and former 
editor of the Annals of Internal Medicine.


While experts agree that tougher trials and similar factors explain some 
of the decline in drugs' reported effectiveness, "something real is 
going on here," said Olfson. "Physicians keep saying that many of the 
new things just aren't working as well," and therefore prescribe 
antidepressant drugs called tricyclics (developed in the 1950s) instead 
of SSRIs (from the 1980s), or diuretics (invented in the 1920s) for high 
blood pressure instead of newer anti-hypertensives.

Whatever the reason for many new drugs packing less punch than old ones, 
that will not keep them from reaching patients.

"The way the drug regulatory system is set up, even if you have just a 
small advance, if you market it right it can be very profitable," said 

Critics of the high prices of drugs that are only marginally (if at all) 
more effective than older, cheaper, often generic medications hope that 
head-to-head studies will persuade more physicians to stop prescribing 
expensive but less effective drugs. The Affordable Care Act of 2010 - 
"Obamacare" - established the Patient Centered Outcomes Research 
Institute (PCORI) to conduct such comparative effectiveness research.

The drug industry says it isn't worried. "Our sector is not concerned 
about objective, high-quality patient-centered comparative effectiveness 
research," said PhRMA's Burkholder. "We believe the substantial value of 
our products will continue to be demonstrated."

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