Everyone would agree that it would be best if we could prevent the development of cancer rather than treat it once it’s there. But thanks to financial incentives, researchers are focused more on treatments than on finding ways of prevention.
The patent systems interact with the FDA’s drug approval system in a way that twists the types of cancer clinical trials that could be done. There are more profits in investing in medication that extends the lives of cancer patients by some months than investing in medicines that would altogether prevent the development of cancer.
This is what economics Professor Heidi Williams of M.I.T. found in her studies. She is also the winner of the MacArthur Foundation “genius” grant. Her study of the problem was conducted in conjunction with another economics professor, Dr. Eric Budish (University of Chicago), and an assistant professor (technological innovation, entrepreneurship, and strategic management), Dr. Ben Roin (also of M.I.T.).
These researchers said that research and development on preventing and treating early-stage cancer are highly valuable from a social perspective. They found that society doesn’t offer much incentive (unintentionally) for conducting such research.
In order to get the FDA’s approval, once pharmaceutical companies have patented a drug, they rush through it to show that their drug is both effective and safe. The faster they are able to get the studies completed, the more time they will have for their patent to remain effective. This is the time when their profit margins are the biggest.
It is faster to develop drugs for treating later-stage diseases than to make drugs for treating early-stage diseases (or preventing disease). Later-stage diseases are more destructive and progress at a very fast pace.
Because of this companies are able to get results faster during clinical trials, even when the results are in the form of tiny improvements in survival.
The same lesson has been offered in some of the medicinal chemistry books. For example, one of these books says that certain chemicals are never developed (into medicines), as the patent-protected production time at hand for recovering the developmental cost is too small.
If FDA is to approve medicines for commercialization, the required clinical trials can take several years. Although a patent can last for 2 decades (excluding extensions), a standard drug enters the market with around 12.5 years of those years remaining.
However, prospective innovators hold some control over the time from receiving the patent and getting FDA approval. This time is referred to as the “commercialization lag.” Innovators minimize this lag by studying those patients in whose case effectiveness and safety can be shown in a shorter time (according to current studies, commercialization lag duration might be decreasing in the case of certain types of drugs).
The study found that more cancer trials have been targeted on treatments in the case of patients suffering from later-stage cancers than for those with early-stage cancers.
During 1973-2011, around 12,000 trials were conducted for later-stage patients who had around a 90% chance of dying within 5 years. On the other hand, just 6,000 trials were targeted at early-stage patients (who had a 30% chance of dying). There were around 17,000 trials involving patients who had the lowest possible chances of surviving (having recurrent cancers.
Interestingly, there were only 500 trials focused on preventing cancer (which has the highest survival benefits). It was also found that the biased approach towards studies that targeted patients with the shortest survival time was much more in the case of trials that were funded privately as compared to public-funded trials.
According to Professor Heidi Williams, her study came to an estimate that around 890,000 life-years were lost in American patients (who had cancer in 2003) because of the commercialization lag’s incentive for investing in drugs that offer short-duration benefits.
There are many ways for addressing the commercialization lag. According to one concept, which is Healthline (currently in Congress), FDA approval should be conferred regularly on finding improved health (that could be measured faster than survival) – the supposed surrogate endpoints, such as cancerous white blood cell counts and characteristics of bone marrow in leukemia research. The measures have a high level of correlation with survival. Therefore, they are more reliable in speeding up leukemia drug trials.
The analysis of Dr. Williams’ study shows that this approach is effective. When cancer drugs are approved depending on certain kinds of validated surrogate endpoints, she and her co-authors saw that the difference between the number of clinical trials based on survival rate vanished. In other words, surrogate endpoints can help in eliminating the bias around the commercialization lag.
Up to now, the sole privately financed drugs for preventing cancer (for which the survival benefits cannot be known for several years), were all approved by FDA depending on surrogate endpoints.
It is controversial to use surrogate endpoints without any solid or known connection to survival. For instance, the prostate-specific antigen test level (evaluated through a blood test), is linked to how much cancer is there in the prostate. However, it is of limited value when it comes to predictive survival in prostate cancer.
Although they may look profitable to drug companies, there will be little confidence in it that drugs receiving approval according to P.S.A. tests would offer survival benefits. According to a current systematic review, almost all surrogate endpoints examined within cancer drug trials have a very weak connection to survival.
Although most cancer drugs have recently been approved depending on surrogate endpoints, most of them feature no or unknown positive survival effects.
The other approach is to lengthen the duration of a medicine’s market exclusivity for compensating for the commercialization lag. According to the Hatch-Waxman Act (1984), it is already permitted to provide a partial extension (6 months for every 12 months) in a clinical trial, with a maximum of up to 5 more years. The analysis by Williams shows that this is the best possible concept. However, there are still several potential drugs that get very short market exclusivity duration.
Under the Affordable Care Act, market exclusivity is granted for 12 years starting from FDA approval. This is 6 months less than the standard 12.5 years remaining on a typical patent. However, it is Cancer Schmancer.
While drug patents are incentivizing innovation, FDA approvals are working as a check on drug effectiveness and safety. But when they come together, it affects the incentives against research. It can reduce the most important thing – preventing cancer.
Via NY Times
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