The world is full of patients suffering from diseases without available therapeutic options and the FDA’s “accelerated approval” pathway offers many an additional degree of hope. Introduced in 1992 and later modified in 2012, the program is not without its downsides.
Accelerated approval guidelines allow investigational drugs to undergo expedited review for the treatment of “serious conditions that fill an unmet medical need whether the drug has an effect on a surrogate or intermediate clinical endpoint.” In clinical trials, a surrogate endpoint is an indicator or sign used in place of another to tell if a treatment works. Instead of stronger indicators, such as longer survival or improved quality of life, surrogate endpoints are something like a shrinking tumor or lower biomarker levels.
While the use of surrogate endpoints in clinical trials may allow earlier approval of new drugs to treat serious or life-threatening diseases, they are not always true indicators or signs of how well a treatment actually works. Which leaves us with the question, is faster better?
The accelerated approval program has attracted a great deal of controversy since its inception. Both drugs and devices are fast-tracked to market without sufficient proof of their efficacy and safety. After the approval process, drug companies are required to perform confirmatory trials to prove the drug is meeting the clinical endpoint.
Of the 93 cancer drugs granted accelerated approval between 1992 and 2017, post marketing requirements were only fulfilled for 55% (in a median of 3.5 years), 40% had not yet completed confirmatory trial(s) or verified benefit, and 5% had withdrawn from the market.
It is no surprise that this quick-on and quick-off the market mechanism for drugs to reach the marketplace has been advantageous for drug companies.
For example, Roche announced the withdrawal for Tecentriq (atezolizumab) after confirmatory trials did not meet their primary endpoint(s) for bladder cancer. The mean cost of this treatment for the drug alone is approximately $244,000 ― not including ambulatory care visits for potential infusions or other supportive care measurements that may be needed while on these drug therapies.
So, what does this mean for consumers and plan sponsors? These medications usually come with a hefty price tag and risky side effects ― without proven benefit. Is it really appropriate to have patients and plan sponsors pay for medications that have not demonstrated long-term clinical benefits or improved survival rates?
The clinical intent of therapeutic interventions is to prolong life or improve a patient’s current condition. You might think taking a “can’t hurt, might help” approach is acceptable, but false hope ― combined with toxic side effects and huge, wasted expenses ― does not seem to be in the best interest of health plans or their plan members.
While pharmaceutical companies are looking for avenues to quickly get drugs in the hands of consumers, the pitfalls of relying on surrogate end points needs a closer look. Faster access to new drugs rarely leads to better outcomes. We would probably be better off if the FDA (and our health plans) continued treating them as experimental until sufficient data demonstrated otherwise.