We Must Keep the Pressure On To Succeed in Global Public Health During COVID and Beyond

The following article is an opinion piece written by Kevin Hershberger and David Wesche. The views and opinions expressed in this article are those of the author and do not necessarily reflect the official position of Technology Networks.

While COVID-19 is still impacting nations globally, we must not forget that other infectious diseases – which could include the next pandemic we face – need attention. If we in the global health community fail to commit time and resources necessary now, we’ll likely find ourselves playing another deadly game of catch-up later.

Infectious diseases claim millions of lives worldwide every year, especially in low and middle income (LMIC) countries. Several of these diseases, including tuberculosis, diarrheal diseases and malaria, have plagued humanity for millennia. In the age ofvaccines, antibiotics and new technologies, these diseases should have been brought under control, yet they still account for more thanone in eight deathseach year.

These deadly diseases are persistent; we cannot let our guard down, especially where people have little means and communities lack adequate sanitation and infrastructure. Addressing infectious diseasesin LMICs poses unique challenges, foremost among them developing regionally effective medications and ensuring access and affordability.

Developing effective medications

Having regionally effective products is the cornerstone of any infectious disease campaign.Whether we are looking to develop drugs at warp speed or repurpose existing medications, the magic is in bringing available technical resources and different regulatory-path strategies, such as the World Health Organization’sCollaborative Registration Procedure, to bear in drug development.

In particular, modeling and simulation (M&S) can help guide and inform development paths, efficient trial designs, decision-making and address equity in drug development by increasing diversity of patient populations included in trials.For example,model-basedmeta-analysisof several thousand trials for COVID-19 treatments increased productivity, informed decisions and enabled swift comparison across several options being evaluated. Ideally, a well-powered, harmonized trial design would effectively ensure all data and resources are efficiently applied to the common goal.

However, while M&S could have played a more critical role in proper dose finding for repurposed drugs for COVID, this step was typically skipped during many of these studies. One of the advantages of biosimulation is that it allows optimizing safe and effectivedoseand treatment duration in diverse patient populationsbeforegoing into human studies. This is especially critical in ensuring that dosing is correct for the patient populations in LMICs, who have historically been excluded from clinical trials and the setting of dosing regimens. The pharmaceutical industry has a poor track record of getting dosing right at product approval, with about80% of drugs having a reduction in dose within 2–6.5 years after approval, but modeling tools can accelerate and streamline trials for patients in LMICs who most need a particular drug, helping select appropriate doses to study and identifying key therapeutic questions to address, such as regimen adjustments.

Promoting access

The most effective medications are useless if patients cannot access them.Not only canM&S be used to advance drug development, but it also has the potential to expand patient access to treatments in LMICs by simulating virtual patients in hard to recruit or special populations and optimizing trial design to expand product labeling.In addition, pandemic-related restrictionsresulted in trial delays, slowing development of new treatment modalities that could have saved lives.M&Scould have immense impact in trial conduct, even under pandemic conditions.

Furthermore, meeting the challenge of equitable access requires investment and funding models that have little commercial return, and yet, since these challenges disproportionately impact LMICs, we must meet them to promote global health. This extends to investing in a strategic physical presence; you cannot administer treatmentsif the people who need them can’t get to you. In addition, strategies developed with agencies and local governments for educating caregivers and patients are critical; differences in culture, processes and communities from place to place will require different treatment paradigms and dosing regimens.

Access also hinges oninfrastructure. A robust supply chain must be able to deliver medicines to remote regions in harsh temperatures and high humidity without cold chain requirements. To help meet this challenge, programs that evaluate and establish product stability in the extreme-heat/high-humidity conditions need to be devised early in the development process. This helps ensure drugs intended for use in LMICs can be delivered with confidence to the patient.

Guaranteeing affordability

The introduction of innovative, diverse drug delivery platforms, including long-acting formulations, targeted drug-delivery systems and fixed-dose combinations, can help address patients’ unmet needs. However, to be successful in the developing world, we need to minutely control the cost of manufacture to make the drugs we create affordable.

Collaboration with drug companies is critical. Together, public health officials and developers can identify localized need, encourage streamlined formulation development with commonly available raw materials, and source local contract development and manufacturing companies with the capability to produce drugs when and where they are needed. This will help promote drug development while keeping costs down.

As we think about how to fight the infectious diseases with which we are familiar and those just over the horizon, consider what we have learned and how it can prepare us. Leveraging collaboration with pharmaceutical companies to promote affordability, working with agencies, local governments and logistics professionals to educate and guarantee access, and making full use of technology to put into practice rapid drug development strategies are approaches that work. They can help us to better fight known diseases and prepare for emerging infectious diseases, so that we're best positioned to save lives worldwide.

About the authors:

Kevin Hershbergeris vice president of integrated drug development at Certera.

David Wescheis vice president of clinical pharmacology at Certera.