Pramod John, PhD, CEO, VIVIO Health, San Leandro, CA;
Q: Some American pharmaceutical companies are well-known for pricing drugs at “whatever the market will bear”. In oncology, some specialty drugs seem to have price tags completely unrelated to the proven effectiveness of the drug. Your company has been taking a lead in confronting this problem. What do you envision as possible solutions?
A: New oncology therapies carry astronomical price tags—most people know this. Receiving far less attention is the question of actual therapeutic value. Drug manufacturers spend billions on advertisements and PR, but unfortunately, real-world patient results are frequently unimpressive. Two recent articles in BMJ make this point, 1) No evidence of benefits for popular oncology therapies and 2) Do cancer drugs improve survival or quality of life?
Why do high-cost oncology therapies with questionable results continue to be prescribed? Let’s examine a situation my company is dealing with right now. VIVIO Health received a request for neratinib, an FDA-approved extended adjuvant therapy for early-stage HER2 positive breast cancer. Our system analyzed all available performance data from sources such as the FDA, ICER and NICE. The drug approval was based on a newly created surrogate endpoint called invasive Disease-Free Survival (iDFS), which only scored 94.2% vs. 91.9% in the placebo arm. Even worse, 29% of the patients dropped out of the trial due to adverse side effects, 16.8% for diarrhea alone. Not surprisingly, the FDA committee patient representatives voted against approval.
Neratinib’s manufacturer PUMA Biotechnologies provided data on the current standard of care, trastuzumab, showing a disease-free survival (DFS) rate of 89%. Interestingly, the use of iDFS as an endpoint led to an increase in the placebo arm of ~3%, which is larger than the neratinib-to-placebo arm difference of ~2%. Ultimately the creation of a new endpoint made a larger impact than the therapy itself. The trial design itself had been altered so many times; the FDA suspected the trial had been ‘unblinded’ and attempted to determine statistically whether unblinding had occurred. Even with these highly questionable results, the FDA approved Neratinib in July.
After being shown the questionable data and asked, “Why neratinib?” the requesting oncologist explained that it’s an FDA-approved drug and “MD Anderson is giving it to everyone.”
Granted it’s hard, but physicians should have the courage to do the right thing. In the context of high-dollar, high-tech therapies and billion-dollar windfalls for pharma execs like Puma CEO Alan Auerbach, physicians must be America’s frontline ensuring that only the right therapies get to the right patients. Using Neratinib as an example, here are seven steps every physician should consider before prescribing oncology therapies:
- Police endpoint games. Don’t allow drug companies to define arbitrary and meaningless endpoints for your patients. Prescribe medications with objective data on meaningful endpoints such as life expectancy. Anything less should be considered experimental at best and pharma should pay for that.
- Do the math. In the case of Neratinib, a 2% probability of potential benefit means that for every 2 patients that might be helped, 98 are subjected to real side effects or other harm. In the neratinib trial, this equates to the ‘lucky’ 33 out of 1,420 total patients, which is quite a needle in the haystack.
- Consider the actual cost. Spending $5M per patient ‘helped’ with such uncertain outcomes makes no sense.
- Consider societal opportunity cost. Spending money on therapies that don’t work diverts dollars away from developing therapies that do.
- Stop listening to key opinion leaders (KOL). Dig deeper and make your own decision. A KOL’s opinion isn’t data and is too often wrought with conflict.
- Require companion tests. Don’t prescribe low-probability therapies without some form of a companion diagnostic and insist that the drug company provide it for you.
- Prescribe therapies as if you’re the patient and you’re spending your own money.
Physicians, you hold the key to changing the cost curve for ineffective therapies. Drug companies will get the message when you refuse to prescribe treatments that don’t work and cost too much.
Pramod John’s contact info is included in the author affiliations at the top of this page.
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