COVID-19 - A Patient Call for Earlier FDA Approvals and the Perfect Time for Healthcare Innovation
The COVID-19 crisis is shining a light on the pace of healthcare advancements in the United States. I’m so happy to see faster-than-usual clinical trial creation for COVID-19 vaccines and I know that the FDA is working incredibly hard. We should all be applauding (and helping!) the heroic efforts of the men and women in our hospitals who are serving patients every day at risk to their personal safety.
Today’s Process Slowdowns
Even with these herculean efforts, we are still most likely a year out (or much more) from seeing an approved vaccine with our current structure. Why? Because the FDA currently requires the following steps to approve a new therapy:
|Phase I||Drug Safety: Is the drug safe to take?||$4.5M cost||Handful of patients|
|Phase II||Efficacy: Does the drug work?||$11.2M cost||Dozens of patients|
|Phase III||Comparison: Is the drug better than “standard of care?”||$22.1M cost||Hundreds of patients|
|NDA Application and FDA approval||$2M cost|
|Phase IV||Long-term impact of side effects, quality of life, etc.||$38.9M cost||Thousands of patients|
(cost data for the average oncology drug approval for a single clinical trial provided by Health and Human Services)
The US healthcare system today uses incredibly slow incremental innovation and today, it takes on average 15-17 years to get a new drug through the drug development and approval process. Of course in bringing new therapies to patients, we are dealing with patients’ lives. Safety is paramount. But what if the safety bar gets cleared? How can we speed things up?
FDA Approval after Phase II Study
Once a Phase II study is run, the safety data has been determined and you know if the drug works, even in a fraction of patients. At this point, the FDA should approve the drug. Then let doctors and patients decide if it is worth using.
Let’s go back over 58 years. You may be surprised to learn that before 1962, new pharmaceutical drugs could be approved after clearing the Phase I safety bar. The 1962 Keefauver-Harris Amendments changed that by requiring efficacy to be part of the FDA’s mandate.
Ironically (for myeloma patients), the amendment was in response to the thalidomide tragedy, where the drug caused birth defects in Europe when their mothers used it for morning sickness in the 1950’s. This was clearly a safety issue, not an efficacy issue.
The drug had not yet been approved in the United States. Senator Kefauver of Tennessee and US Rep Harris of Arkansas required drug manufacturers to show both safety and efficacy and it was signed into law by John F. Kennedy. FDA reviewer Frances Oldham Kelsey refused to approve thalidomide in the US.
It wasn’t until 1998 that it became approved for a complication of leprosy. Then in 2006 it was approved for multiple myeloma and remains a core drug class for myeloma patients (thalidomide, lenalidomide, pomalidomide, etc).
That’s a 50 year journey to find an effective drug for a terminal cancer. What a waste of time. What if its negative effects on pregnancy had been isolated and the drug been tested for a variety of conditions? Myeloma patients may have been able to try thalidomide in the 1950’s instead of the clinical trials that were then comparing Coke vs. urethane (a real myeloma study!).
According to Charles Hooper, President of Objective Insights, Inc. and David Henderson, a research fellow with the Hoover Institution and former senior health economist with President Reagan’s Council of Economic Advisors, in the Wall Street Journal:
Further, the Kefauver-Harris Amendments dramatically increased the time and cost of getting new drugs approved. Evidence provided by University of Chicago economist Sam Peltzman suggests that the number of new drugs approved dropped by 60% in the decade following the law change. We have fewer ineffective drugs, but also far fewer effective ones than we could have had.
Although a drug passes through today’s lengthy and expensive FDA clinical trial process, patients in the real world still have to see whether the drug will work for them. For example, lenalidomide works marvelously for some myeloma patients, but others have severe reactions.
This is the real world data that truly matters at the end of the day. The FDA doesn’t not need to duplicate expansive efficacy data. If it passes a Phase II study that shows it works for any patients, we can use real world data to figure out which patients will benefit the most from the drug.
I wanted to see this sort of data when I was diagnosed with multiple myeloma in 2010. I was trying to make life and death decisions with my doctor for my care. This is why we built HealthTree (www.healthcare.org). It is a tool for myeloma patients to use to navigate their care, but it also aggregates our shared myeloma experiences to provide data to both researchers and patients about myeloma drug efficacy and outcomes. We can now see early indications of efficacy in certain patient populations (by genetics, co-morbidities, etc.) with aggregated data in myeloma and we can tell quickly what is and isn’t effective - and for whom.
Just like in myeloma, we need fast efficacy data for COVID-19 solutions. We are currently replicating part of HealthTree for COVID-19 for cancer patients. And we will be launching a COVID-19 study specifically for myeloma patients in HealthTree. Solutions like remdesivir (known to be generally safe), hydroxychloroquine with or without azithromycin, or other such therapies could be tested rapidly to see if they work and for whom.
Mr. Hooper and Mr. Henderson have valid points about sticking with the “standard” process for an emergency like COVID-19:
These clinical trials take time, and they still won’t answer many of the questions doctors have about the drug’s use against Covid-19 now. What’s the right dose to get remdesivir into the lungs? How early should it be given? If it is given to sick patients already on ventilators in hospitals, will it help? All these things will depend on the individual patient.
I agree that this process change is just as needed in myeloma or other terminal diseases as it is for COVID-19 and that today we have “a critically flawed approach to medicine.”
Perhaps we could spare ourselves another 50 years of drug development for future viruses and terminal diseases with the change.