Dr. and Coach Catana Starks, the coach profiled in our film From the Rough, passed
As I have watched reporters, Dr. Anthony Fauci, the President, and others try to figure out the role Chloroquine (the anti-malarial drug) and other drugs might play in reducing the number of Coronavirus deaths and serious illnesses, I realized that they are speaking from very different frames of references and paradigms.
There are two completely different paths to succeeding against the Coronavirus:
- Multiple customized or precision treatments can be developed and deployed by individual physicians or groups of physicians who repurpose existing approved drugs approved by the FDA for other illnesses or diseases. The use of these drugs for something other than their approved “indication” or use is called an “off-label” use. The FDA does not control what individual clinicians do and it cannot prohibit them from doing so.
- A new, standardized vaccine or drug that either prevents or “cures” the Coronavirus or most of its cases that is developed by a pharmaceutical company and approved by the FDA. The FDA has complete control over the marketing, production, and distribution of a drug by a pharmaceutical company and must approve any new drug introduced into the market. It requires a multi-stage clinical trial before the non-clinical trial populations can use the drug.
There is a “compassionate use” exemption for individuals not eligible for a clinical trial for drugs that are deemed safe but have not concluded the clinical trial process.
However, we have ample precedents for more customized repurposing of drugs that are approved for one use and deployed successfully by treating physicians for other uses.
Precedents for a more customized approach to controlling diseases and illness
In 1971, President Nixon announced a “war on cancer” which was addressed in the National Cancer Act of 1971 The paradigm on which he was operating was that cancer was a single disease.
We now know that the term “cancer” is an umbrella term for uncontrolled growth and slower deaths of cells. We also know that the cancers in every victim follow a different “pathway” and therapies have to be customized for many cancer victims. Our way of thinking about “cancers” is very different from what we understood in 1971.
Oncologists buy their own medications, customize them for many patients, and administer them in different doses over different time periods. They also adapt their treatment plans based on how the patient’s body and the tumors respond. In recent years, they do genetic profiling of the tumors to gain better insights. This article talks about how Mount Sinai researchers experimented with and used “drug cocktails” as targeted cancer therapies.
The death rate for HIV/AIDS has been brought down to the point where this diagnosis is not the automatic death sentence that it once was. This is what was done in the 1990’s to reduce the death rate for HIV/AIDS.
Here is where we are now on HIV/AIDS, which has 40,000 new cases a year.
“Today, these are the facts about HIV/AIDS.
- There is no cure for HIV, although antiretroviral treatment can control the virus, meaning that people with HIV can live long and healthy lives.
- Most research is looking for a functional cure where HIV is reduced to undetectable and harmless levels in the body permanently, but some residual virus may remain.
- Other research is looking for a sterilizing cure where HIV is eradicated from the body completely, but this is more complex and risky.
- Trials of HIV vaccines are encouraging, but so far offer partial protection only.”
We do not hear much about HIV/AIDS because of the widespread use of “antiretroviral treatment.” We did not “win the war on HIV/AIDS.” We stopped its advance and converted casualties from deaths to chronic disease patients.
More recently, the World Health Organization sponsored a clinical trial to develop targeted drug therapies for controlling the deadly Ebola virus outbreak.
What clinicians and researchers did in all these cases is practice a form of “personalized” or “precision” medicine.
Dr. William Grace of Lenox Hill Hospital, who was interviewed on two different news programs, is actually an oncologist who is quite comfortable mixing and matching existing anti-viral drugs to treat Coronavirus patients. He is practicing a form of personalized medicine.
It is entirely possible that hundreds of different specialists may develop hundreds or thousands of customized combinations of existing drugs developed or “indicated” as treatments for other diseases or illnesses. They may end up being successful in treating multiple subsets of the seriously ill Coronavirus population and significantly reducing the death rate. However, they would not have succeeded in developing a “cure” or a “vaccine” for the Coronavirus.
Last evening, Dr. Martin Makary of Johns Hopkins University specifically took issue with any characterization of the anti-malarial drug therapy as being only supported with “anecdotal evidence.” He said that many clinicians are reporting success rates in reversing severe illness cases consistent with what Dr. Grace has reported.
More recently, clinicians and research scientists are successfully transferring blood from recovered Coronavirus patients to seriously ill patients. This therapy may only work for a six-month period, but it will relieve the stress on overloaded intensive care systems.
Other therapies will emerge from the innovation of clinicians working together with researchers, some of which are beyond our imagination, but they will reduce the lethal impact of this virus.
More standardized vaccines and therapies
On the other hand, Dr. Fauci and others who work with pharmaceutical companies are on a completely different path. Their goal is to develop and deploy a standardized vaccine to prevent the Coronavirus from infecting people or a standardized therapy to treat seriously ill Coronavirus patients. The pharmaceutical companies must do multi-stage clinical trials and secure FDA approval before they can produce and do mass marketing of a new drug. That takes a long time, and the odds of success are relatively low.
Seasonal influenza vaccines are developed and deployed faster, and they generally work for most variants of the influenza virus.
Both treatments and vaccines that are developed by pharmaceutical companies and that secure FDA approval are designed to be more standardized treatments against pathogens (viruses, bacteria, or fungi) that are sufficiently similar that a single drug can treat them.
Why President Trump and Dr. Fauci are not inconsistent but are referring to completely different treatment approaches.
President Trump is celebrating the entrepreneurial and rapid deployment of these customized treatments that physicians are using for their particular patient populations. He is expressing an opinion that enough physicians can find enough of these customized off-label therapies that the number of deaths can be reduced to a very low level.
He is not claiming that this path will lead to the FDA approval of a standardized vaccine treatment in the next few months because that cannot happen. The testing and FDA approval process would take that well into late next year and probably later.
Dr. Fauci acknowledged today that physicians might develop multiple customized treatments using combinations of existing approved drugs that might work on subsets of the Coronavirus patient population. He uses the unfortunate term “anecdotal,” which tends to confuse the non-medical person. The successes that Dr. William Grace and others are achieving are not individual stories, but treatment paths that are working in dozens, if not hundreds of cases.
However, Dr. Fauci is cautioning us to recognize that these successes are not vaccines, standardized treatments, or “cures.” In fact, we may find that no standard vaccine or treatment will ever be developed.
It is possible that the path for controlling the Coronavirus for the most seriously ill patients may end up with an outcome in which we do not eliminate the virus or develop early immunities to it, but may get rid of its most life-threatening symptoms for enough people that we can resume normal activities sooner.
Is President Trump peddling “false hope” by telling the public he is optimistic? Not at all, if what he is saying is that he has total confidence that our best physicians can develop customized therapies to reduce deaths and to control serious illnesses. To have customized therapies usable to reduce the deaths significantly is truly a “game-changer.” His goal is to reduce the lethal impact of the disease, not to contain its spread. We have three separate examples from cancer, HIV/AIDS and Ebola treatments that support what he is saying.
He has not claimed, nor can he claim, that there is any quick fix to eliminate infections or to destroy the Coronavirus.
Accordingly, Dr. Fauci is correct that we should not expect anything that eliminates the Coronavirus infection pandemic any time soon. His recommendations on social distancing and harsh social isolation may be the only workable strategies for reducing the spread of the disease. His goal is to reduce the spread of the disease so that the efforts to treat it do not overwhelm our healthcare system. We can debate whether this social distancing should be universal or just limited to vulnerable populations, but it is the best available temporary very near-term strategy.
If the members of the media do not understand this, it is understandable. Very few people understand or can relate to “personalized medicine” and targeted drug cocktails because it goes against much of the way we think about illness or disease.
We put labels on combinations of symptoms because we want a simple way to describe something that may be complex and non-standard. The idea that you and I can go to the same doctor, be told that we have the same disease or illness and be prescribed two completely different treatments, each of which is right for us, is hard to reconcile with what we see every day online and hear in conversations people have about illnesses and diseases.
What President Trump is highlighting is the only short and medium-term option for treating many seriously ill patients. The use of off-label anti-viral medications to treat patients is too expensive, even though the medications are not expensive, because of the healthcare infrastructure required to deliver them and the level of research and small-scale testing at the clinician and research scientists level required to validate them.
However, these customized treatments will keep many people from dying and will reduce the strain on the hospital system, but we need strategies in addition to them, including vaccines and broad-based therapies.
If these customized therapies work to reduce deaths and serious hospitalizations, we will see a big boost in morale and a more positive response from the financial markets, even while we are sheltered in place.
How might we deploy these customized therapies?
We require a much more in-depth understanding of what the “vulnerable population” looks like. Artificial intelligence tools are able to do this. Those individuals should be targeted to receive these anti-viral therapies earlier and more systematically, because they are the ones most likely to progress to serious illness and death, especially younger people with long life expectancies.
Dr. David Katz of Yale, whom I know, has developed a sophisticated risk stratification model to assess who needs what kind of public health and clinical intervention. Governor Cuomo referred to this as a “more productive, less destructive public health strategy.”
We have to make sure that we pay close attention to advance directives and recognize that providing anti-malarial drugs to someone in his state of health may be inconsistent with his wishes and values. We do not have the luxury of extending lives at all costs, given scarce resources.
Conversely, we need to start gathering data to be able to invite some other people back into everyday life. As Governor Cuomo recommended in his Sunday, March 22, 2020, daily briefing, we also need to identify those who have recovered and have developed antibodies to send them back to work, particularly if they are healthcare workers.
Moreover, we should have standard dis-infecting and distancing protocols for places that reopen, so they do not become transmitters of the Coronavirus. Israel is putting healthy teenagers to work to do rigorous and frequent cleaning of highly frequented public spaces. As Governor Cuomo said at his March 23 daily briefing, we need a plan on an early pivot to get people back to work.