These unprecedented times remind us of the importance of science and clinical research in developing our understanding of new threats and, most of all, how to combat them. As seen in past pandemics, efforts are placed on experimental medicinal products in an attempt to treat patients – increasing the need and importance of these clinical studies. Clinical research informs evidence-based clinical practice, providing for improved delivery of interventions and better health outcomes. Both assist in generating practice guidelines that apply to a broader population of patients who benefit the most from clinical research.
In the midst of the Ebola outbreak in 2014, the World Health Organization (WHO) ethics working group stated that there is an ethical obligation to conduct research during an epidemic and that research should be a component of the public health response. UNESCO asserted that increasing the knowledge base about Ebola and the various treatment methods was the only way to ensure resources were being used efficiently and that efforts were improving patient outcomes. Clinical studies and experimental medicinal products played a key role in managing the Ebola outbreak. Infected international aid workers were given unproven therapeutic agents and appeared to survive at higher rates. This initiated the call to make potential therapeutics available for the thousands suffering from Ebola. Once the WHO declared the epidemic a public health emergency of international concern, several teams began conducting formal clinical studies to identify potential therapeutics and vaccines. These trials did not only address the short term need for treatment but created the foundation for further research, enabling the development of REGN-EB3 and mAb114, both harvested antibodies from convalescent patients, which were found to be 89% and 90% effective, respectively.
The Need for Clinical Research in Managing Viral Outbreaks
Research and development for pandemic infections like COVID-19 or Ebola are generally not a top priority until there is a global threat that necessitates studies to evaluate therapeutics and vaccines. The World Health Organization has recognized that “when assessing a new infectious disease outbreak, it is of utmost importance—but enormously difficult—to quickly estimate its key characteristics, such as how the infection spreads, clinical severity, clinical presentation, the natural course of the illness, mortality and the risk factors associated with infection”. This information is pivotal for determining appropriate decision making that will address the issue at hand and will assist in finding solutions to the threat. The knowledge acquired in these studies is paramount to understanding the facets of the infection outbreak: determining ongoing preparedness and responses, informing revisions of current diagnosis, treatment protocols and advancing patient care in real-time, and identifying the at-risk groups.
Clinical research is particularly difficult in the midst of an outbreak or pandemic. This knowledge can only be developed if there is capacity in place to conduct research that meets scientific, regulatory and ethical standards. Similarly, to public health measures, the importance and focus of international logistics are frequently discounted in the absence of a crisis. This plays a crucial role in successfully executing a response and conducting research. In an outbreak scenario of a rare or novel pathogen, like the one we currently find ourselves in, this task becomes increasingly challenging. With limited knowledge about the pathogen or infectious agent, patient diagnosis, management and prevention, prioritization becomes nearly impossible. Clinical research plays a crucial role in designing better control measures and Bowhead Health intends to tackle this issue amid this escalating pandemic. The Bowhead platform will expand the reach of clinical studies and simplify the process of linking participants to relevant research that aims at answering critical questions. Streamlining the communication between leading epidemiologists, clinical researchers, public health and participants will facilitate the collection of valuable research data from affected individuals. The collected information will help to better understand the behavior of COVID-19 locally and globally. It will assist decision makers in preparing our health systems for future health crises.
Clinical research and clinical care are sometimes seen as being mutually exclusive. However, clinical research benefits future patient care. Patients who enroll in clinical studies often benefit from receiving better medical care than patients who aren’t enrolled due to better follow up and the potential to benefit from new and improved medicines. The number of registered clinical research studies has increased fourfold over the past decade, with over 330,000 studies registered as of March 31st, 2020. The success of a study, measured in the probability of a medication being approved has also increased 8.6 percentage points over a three year period, with studies investigating infectious diseases increasing by 25.2 percent. Additionally, healthcare decisions in a research setting are not based solely on the interactions between a provider and a patient, but rather are controlled, regulated and standardized.
Medical Countermeasures and the FDA’s Response
In response to the Ebola outbreak in 2014, health officials from around the world collaboratively developed the Global Health Security Agenda. This plan outlined the critical effort to strengthen national and global systems, improving the prevention, detection, and response to infectious disease threats. The US Food and Drug Administration (FDA) engages in a variety of efforts to support global health security, and have developed medical countermeasures (MCMs) to better respond to global infectious diseases and public health emergency threats. These countermeasures are aimed at countering the human health effects of chemical, biological, radiological and nuclear threats, as well as emerging infectious disease threats. In attempts to detect, diagnose, and mitigate emerging threats the FDA has approved and authorized the emergency use of uncleared diagnostic devices. In the case of promising, but unapproved novel diagnostics the FDA uses Emergency Use Authorization (EUA) to authorize the use of tests to strengthen domestic laboratory capacity and public health preparedness.
This strategy has been used in addressing the current pandemic but unfortunately there were some problems. By early February, all testing for COVID-19 in the US was being conducted at the CDC. However, a set of test kits sent to 50 test centers returned inconclusive results. The ineffectiveness of these tests came at a crucial time and resulted in substantial shortages of test kits. A public health emergency was declared on February 4th, invoking a new regulatory regime requiring EUA. Limiting who can develop new tests at such a critical time may sound counterintuitive, however, it ensures that only carefully vetted labs are able to take part in development. According to Joshua Sharfstein, a former principal deputy commissioner of the F.D.A., this limits the ability for “Any lab (to) advertise a coronavirus test”, increasing accountability and thus better managing the pandemic response.
Overall, new drug development is a meaningful and important task that has some risks. The medicines developed through clinical trials have improved health and quality of life on a global scale. Bowhead Health recognizes the importance of clinical trials and is developing a comprehensive tool to identify the trail best suited for improving reported patient outcomes on an individual and global scale. The digital tools developed facilitate the acquisition of critical data that will help to mitigate the risks of developing new medicines. Bowhead tools allow the efficient enrollment of study participants, which is a critical component of clinical research and many times deficient enrollment results in costly delays in the implementation of clinical studies. Additionally, the tools developed by Bowhead assist in the ethical collection and analysis of participants data.
Sources
https://academic.oup.com/biostatistics/article/20/2/273/4817524
https://clinicaltrials.gov/ct2/resources/trends
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171126/
https://prais.paho.org/en/current-information-on-fda-actions-in-response-to-covid-19/
https://www.newyorker.com/news/news-desk/what-went-wrong-with-coronavirus-testing-in-the-us
https://www.ncbi.nlm.nih.gov/books/NBK441674/
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(19)30829-1/fulltext
