Chloroquine may never get the perfect study proving it's good. Use it anyway

Most folks have read tantalizing reports of patients who have received a combination drug cocktail of chloroquine (or hydroxychloroquine), azithromycin (commonly known as a Z-pack), and sometimes zinc for treatment of COVID-19.  These reports have been mostly anecdotal and have involved small numbers of patients.  But there have been a decent number of such reports — enough to spark President Trump's interest and endorsement. 

And if you personally know and speak to any physicians — particularly hospitalists, pulmonologists, intensivists, E.D. physicians, or primary care physicians — you'll soon find someone who has quietly prescribed this drug cocktail to one or many patients.  The reports I've received from physician colleagues have invariably been positive.  In addition, virtually all physicians I know would not hesitate to treat their own family members with the CZZ cocktail.

The FDA has been quite hesitant to approve such treatment — even though it's a long known and approved practice for physicians to prescribe drugs "off label" — in other words, to use drugs for a purpose other than their specific FDA-approved use.  Docs aren't jailed for doing that!  The exercise of physician judgment is a recognized and accepted principle and practice.

The reason for the FDA foot-dragging is generally understandable under most circumstances: there is no current Level I clinical data that supports the use of these drugs to treat COVID-19.  As mentioned above, the reports have all involved a small number of patients and are simply anecdotal in nature.  And there is always valid concern about risks and side-effects of drugs.

Level I clinical data generally — not always, but generally — involves a randomized, prospective, double-blind study.  Such studies are carefully planned, organized, and conducted.  There is typically a treatment group — the patients who receive the treatment — and a control group — a well matched group of patients who receive a placebo, not the actual treatment.  Such studies take time.  That's the first problem.

In a pandemic, we don't have the luxury of a lot of time to conduct an exquisite study.  Lives are immediately at stake.

A second potential problem is the risk of side-effects from the use of any drug.  However, both drugs in question have been in use for many years and have a well known and reasonable risk profile.  It's not as if we're testing brand new drugs.

There is a third problem.  To do a really strong Level I clinical study, the study population would ideally need to consist of the high-risk population group — older patients with one or more significant co-morbidities.  In a younger healthy population, COVID-19 is more likely to be a benign disease process even if not treated.  So there is a reasonable chance that investigators wouldn't be able to demonstrate a clear and persuasive drug treatment advantage even if there is one.  To do so would require an immense study population.

Finally, there's a fourth problem with a Level I clinical study that I haven't heard discussed.  At the current point in time, it is this: 

By raise of hand, who among you who are in the high-risk population group wants to contract COVID-19, agree to participate in a study, then volunteer to take your 50/50 chance of being assigned to the control group?  Anyone?

I know there are studies underway to evaluate this drug combination.  But I would hope the FDA would consider loosening its otherwise tight control — perhaps if even on a temporary basis — to allow treatment that can be evaluated on a real time ongoing basis.  It's not Level I clinical data, but for the reasons listed above, we may never achieve Level I clinical data — at least not in the necessary time frame.  And sometimes emergent need trumps standard procedure.

Most folks have read tantalizing reports of patients who have received a combination drug cocktail of chloroquine (or hydroxychloroquine), azithromycin (commonly known as a Z-pack), and sometimes zinc for treatment of COVID-19.  These reports have been mostly anecdotal and have involved small numbers of patients.  But there have been a decent number of such reports — enough to spark President Trump's interest and endorsement. 

And if you personally know and speak to any physicians — particularly hospitalists, pulmonologists, intensivists, E.D. physicians, or primary care physicians — you'll soon find someone who has quietly prescribed this drug cocktail to one or many patients.  The reports I've received from physician colleagues have invariably been positive.  In addition, virtually all physicians I know would not hesitate to treat their own family members with the CZZ cocktail.

The FDA has been quite hesitant to approve such treatment — even though it's a long known and approved practice for physicians to prescribe drugs "off label" — in other words, to use drugs for a purpose other than their specific FDA-approved use.  Docs aren't jailed for doing that!  The exercise of physician judgment is a recognized and accepted principle and practice.

The reason for the FDA foot-dragging is generally understandable under most circumstances: there is no current Level I clinical data that supports the use of these drugs to treat COVID-19.  As mentioned above, the reports have all involved a small number of patients and are simply anecdotal in nature.  And there is always valid concern about risks and side-effects of drugs.

Level I clinical data generally — not always, but generally — involves a randomized, prospective, double-blind study.  Such studies are carefully planned, organized, and conducted.  There is typically a treatment group — the patients who receive the treatment — and a control group — a well matched group of patients who receive a placebo, not the actual treatment.  Such studies take time.  That's the first problem.

In a pandemic, we don't have the luxury of a lot of time to conduct an exquisite study.  Lives are immediately at stake.

A second potential problem is the risk of side-effects from the use of any drug.  However, both drugs in question have been in use for many years and have a well known and reasonable risk profile.  It's not as if we're testing brand new drugs.

There is a third problem.  To do a really strong Level I clinical study, the study population would ideally need to consist of the high-risk population group — older patients with one or more significant co-morbidities.  In a younger healthy population, COVID-19 is more likely to be a benign disease process even if not treated.  So there is a reasonable chance that investigators wouldn't be able to demonstrate a clear and persuasive drug treatment advantage even if there is one.  To do so would require an immense study population.

Finally, there's a fourth problem with a Level I clinical study that I haven't heard discussed.  At the current point in time, it is this: 

By raise of hand, who among you who are in the high-risk population group wants to contract COVID-19, agree to participate in a study, then volunteer to take your 50/50 chance of being assigned to the control group?  Anyone?

I know there are studies underway to evaluate this drug combination.  But I would hope the FDA would consider loosening its otherwise tight control — perhaps if even on a temporary basis — to allow treatment that can be evaluated on a real time ongoing basis.  It's not Level I clinical data, but for the reasons listed above, we may never achieve Level I clinical data — at least not in the necessary time frame.  And sometimes emergent need trumps standard procedure.