Current clinical trials were already stressed to function in a timely manner prior to Covid-19. Perpetual supply chain disruptions, in-person discontinuances, and constantly changing regulatory amendments make it very difficult for clinical trials to run effectively. With Covid-19, clinical trials are now completely disrupted. However, there are specific ways in which clinical trials can regain traction. These include developing virtual clinical trials and activating Emergency Use Authorizations (EUAs) by the Food and Drug Administration (FDA) to continue clinical trials in order for patients to have access to life saving emerging drugs.
Supply Chain Disruptions
Currently, the U.S. is reliant on pharmaceutical manufacturing from other countries. In particular, the U.S. is largely dependent on China for important pharmaceuticals. These drugs include traditional small molecule medications but also emerging biologics. About 60% of shortages were attributed to supply disruptions due to manufacturing and/or quality problems in 2019”.2 From 2017 to 2018, the FDA reported an increase in the number of drug shortages. These shortages can be long and, in some cases, are delayed up to eight years.2
COVID-19 was the tipping point into total chaos. Due to the pandemic, pharmaceutical drug distribution is in disarray. Labor shortages quarantined staff, and port disruptions are major contributors to the now severe disruption for supply chains. As many as 57 drugs made by large and small pharmaceutical companies are at risk due to Covid-19-induced restrictions in China.2 The most apparent disruption is, an active pharmaceutical ingredient, which is made in one country, must then be shipped to another for final formulation. Unfortunately, alternative manufacturing and distribution options are extremely expensive (up by 225%).2 Thus, as the Covid-19 pandemic is projected to continue into the near future, it is unclear how severe supply chain disruptions will impact on people’s well-being.
Virtual Trials Ahead
Virtual trials are a way to overcome the difficulties that Covid-19 has created. The virtual method is composed of approaches such as “the use of telemedicine, video/online meetings, telephone monitoring, wearable health, direct-to-patient delivery and sample pickup services, and decentralized laboratory facilities” 2
There are a multitude of benefits that come with virtual clinical trials. One of the longer-term benefits is that virtual clinical trials “reduce unnecessary trips to hospitals, making trials more convenient for patients who are giving their time and energy.” 3 In turn, studies will gain increased important information due to the higher number of enrolled participants. As a result, virtual trials can potentially provide more meaningful and more statistically significant information compared to traditional trials limited to participants who can travel. Over 50% of patients are more likely to participate in a trial if home care is offered.
Another benefit of virtual clinical trials is cost. Typically, 40 to 60 % of a traditional clinical trial budget goes towards investigators.4 As virtual clinical trials will require fewer physical sites, fewer investigators to be hired is anticipated. On-site monitoring by nurses and staff makes up another 25 to 30% of the costs for traditional clinical trials. By reducing the number of investigators sites, the cost of on-site monitoring and management is significantly reduced. The use of remote-monitoring also reduces the cost for site monitors and all the travel, hourly rates, and expenses associated with all the personnel involved.4 Therefore, the ability of virtual trials to provide faster and more meaningful studies has the potential to not only be cost-effective but also accelerate the rate of drug approvals and patient access.
EUA May Save Current “brick and mortar” Clinical Trials
An EUA permits the FDA to “help strengthen the nation’s public health protection against chemical, biological, radiological (CBRN) threats by facilitating the availability and use of medical countermeasures (MCM) required in public health emergencies.” 5 A significant amendment to the Federal Food, Drug, and Cosmetic Act was made in 2013, with the creation of the Pandemic and All-Hazards Preparedness Reauthorization (PAHPRA). The PAHPRA allows for “the FDA to waive otherwise applicable manufacturing requirements to accommodate emergency response needs.”6 The amendment also enables the FDA to dispense MCM’s during a CBRN emergency without requiring an individual prescription for each recipient of the MCM.6 Using this amendment, the FDA could potentially enable clinical trials to successfully complete trials for anti-Covid-19 therapies or vaccines faster and more efficiently, which will provide patients access to these much-needed medications. For clinical trials testing therapies focused on non-Covid-19-related illnesses, they could also be completed in a timely manner. Thus, the EUA is an effective tool the FDA can use to provide the necessary framework to guide clinicians and sponsors conducting clinical trials during the pandemic.
The pandemic has triggered a necessary change in clinical trial design and management. Covid-19 has caused a significant disruption in providing everyday people and sick patients in hospitals with access to pharmaceuticals. However, virtual clinical trials may emerge as a viable alternative to in-person trials. Ongoing clinical trials may also benefit from the use of the EUA by the FDA. The degree of impact that Covid-19 has had on clinical trials is still ongoing and won’t be realized until this pandemic is over. But at least there are preparations in place to ensure the continued health of the global population.
Bioinsider is hosting an intimate and informal Friday Roundtable Event on Friday, Nov. 6 to discuss some of these critical topics, “Addressing Bioanalysis in Clinical Trials during COVID-19” from 11:45 AM EST to 1:00 PM. You can sign up for FREE and join this discussion to share your thoughts here.
1 U.S. Dependence on Pharmaceutical Products From China. (2019, August 14). Council on Foreign Relations. https://www.cfr.org/blog/us-dependence-pharmaceutical-products-china
2 Alvaro, D. (2020, September 29). The COVID-19 Pandemic Magnifies Pharmaceutical Supply Chain Issues. Pharma’s Almanac. https://www.pharmasalmanac.com/articles/the-covid-19-pandemic-magnifies-pharmaceutical-supply-chain-issues
3 Sukirti, K., & Newbould, C. (2020, August 25). Adapting clinical supply practices during Covid-19. European Pharmaceutical Manufacturer. https://www.epmmagazine.com/opinion/adapting-clinical-supply-practices-during-covid-19/
4 Measuring The Financial Impact Of Remote (Digital) Clinical Trials. (2019, January 29). Clinical Leader. https://www.clinicalleader.com/doc/measuring-the-financial-impact-of-remote-digital-clinical-trials-0001
5 Emergency Use Authorization. (2020, November 2). U.S. Food and Drug Administration. https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization
6 PAHPRA MCM Provisions. (2019, December 6). U.S. Food and Drug Administration. https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/summary-pahpras-mcm-provisions