March 30, 2020

COVID-19 Therapies: Time is of the Essence and Knowledge is Power

In the battle against COVID-19 in the United States, we are in the race of our lives.

In the battle against COVID-19 in the United States, we are in the race of our lives. Or should I say the race for our lives.

With the current terrifying trajectory we’re on in the U.S., time is of the essence. Time is of the essence with respect to social distancing practices to mitigate the numbers of people that get infected with COVID-19, risk to the wellbeing of our healthcare workers due to insufficient supplies of personal protective equipment (PPE) (#GetMePPE), inadequate numbers of ventilators, likelihood of our healthcare system capacity being overwhelmed, and projected numbers of COVID-19-related deaths based on epidemiologic modeling. I say again, time is of the essence. Indeed, we are at a critical juncture with this pandemic, where we must soon turn the corner to be able to successfully address the many known problems. Also, not to be under appreciated are the not yet fully anticipated challenges being brought on by this pandemic.

In this THCQ Consulting Health Care Quality Insights Blog article, I speak of one such topic – that of the conduct of non-placebo-controlled clinical trials to evaluate the comparative effectiveness for already available drugs in the marketplace that are prospective new therapies to treat COVID-19. More specifically, this article focuses on the speed and efficiency of the conduct of prospective, comparative effectiveness COVID-19 clinical trials. Lives can indeed be saved when clinical trials are conducted with the highest levels of scientific integrity and executed with speed, efficiency, and real-world relevance.

Rationale and Purpose for Writing on this Topic

Over the course of my career, I was involved in the conduct of clinical trials for 15 years across three pharmaceutical companies, with a subsequent focus over the last 10 years on new innovations in value-based healthcare delivery and data solutions introduced into healthcare as a result of the Affordable Care Act.

It is with this perspective and purview that I propose a novel clinical trial methodology that will enable the time-efficient generation of real-world clinical evidence at the point-of-care in our U.S. hospitals. The idea is to apply this point-of-care clinical trial (POC-CT) methodology to studies that involve already available drugs in the marketplace that are potential new therapies for the treatment of COVID-19.

Traditional Clinical Trial Versus Novel Point-of-Care Clinical Trial (POC-CT) Approach

We are all keenly aware of the desperate need for the time-efficient establishment of new safe and effective treatments of COVID-19. This methodology is best suited for the testing of active treatments and not as well suited for testing of vaccines. Clinical trial testing is the final evaluative pathway by which such investigative agents are assessed by the FDA for their safety and efficacy. In delivering on clinical trial testing, traditional approaches to clinical trials generally achieve their intended aim from a methodological standpoint.

I contend, though, that for comparative effectiveness testing of drugs already on the market with potential activity against COVID-19 that a novel, rapid data generating, point-of-care clinical trial (POC-CT) approach is warranted and should be given serious consideration. Such an approach will allow for data generation with important advantages compared to traditional clinical trials (see Table 1).

Table 1. Advantages of Data Generated from a Point-of-Care Clinical Trial Versus a Traditional Clinical Trial
Where Did the POC-CT Model Originate? Learnings from Veterans Affairs

The 2011 Clinical Trials article, authored by the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Veterans Affairs (VA) Cooperative Studies Program in the VA Boston Healthcare System, effectively serves as an instruction manual for the POC-CT model (e.g., defined study prerequisites, study design, methodology, study conduct, etc.). So, I will not use space here to fully describe the model. The best way to fully appreciate the point-of-care clinical trial model and its benefits is to read the Fiore et al. article. In brief, though, it is important to share several essential features of the POC-CT model as applied in the VA system.

Table 2. Features of the POC-CT Model
Innovative Partnerships to Expand POC-CT Model to Non-Veteran, U.S. Hospitals

While the Fiore et al., MAVERIC VA paper lays an important foundation for execution of a POC-CT, the conceptualization, design, and conduct of a POC-CT in the VA, U.S. hospitals that are non-VA will require innovative partnerships of a different nature. The good news is that all of the requisite types of organizations, technology, and infrastructure for a POC-CT currently exist. The challenging news is that the requisite organizations will need to form new types of partnerships.  These partnerships will need to be formed with the principle aim to coordinate, plan, design, and execute a POC-CT to address critical clinical questions related to use of proposed new therapies to treat patients with COVID-19 infections.

In normal times, there may not be sufficient motivation to invest the energy to form such partnerships to conduct a new model clinical trial methodology. These, however, are not normal times. Lack of motivation should not prove to be a barrier to such solutions if the approach is thought to be a valuable real-world data generation model to help effectively combat the COVID-19 pandemic.

Table 3. Lists the required types of partnering entities and their respective roles in the conduct of POC-CT model studies

Important Clinical Questions Well-Suited for Study in POC-CT Model Related to COVID-19 and Evaluation of Efficacy and Safety of Investigative Treatments

  1. Does the combination of hydroxychloroquine (PLAQUENIL®) and azithromycin (ZITHROMAX®) demonstrate efficacy and cardiovascular safety in patients infected with COVID-19?
  2. What is the demonstrated efficacy and cardiovascular safety of hydroxychloroquine (PLAQUENIL®) and azithromycin (ZITHROMAX®) in hospitalized patients at different stratified levels of severity of COVID-19-induced pneumonia?
  3. What hydroxychloroquine dosing regimen achieves optimal balance of efficacy and safety in hospitalized patients with COVID-19-induced pneumonia?
  4. Other questions related to investigative COVID-19 therapies that heuristically and empirically arise from frontline clinicians who are treating patients with COVID-19.
For reference to COVID-19 clinical drug trials that are currently planned, ongoing, and recently completed, such information may be accessed at Clinical

In summary, time is of the essence and knowledge is indeed power in the race for safe and effective COVID-19 therapies. The POC-CT model offers a potential new means by which to gain critical time and generate valuable knowledge in combating the COVID-19 pandemic and hopefully in helping save lives.

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