The COVID-19 vaccines that have been developed over the past year are truly remarkable, with data showing efficacy rates rarely seen—but often hoped for—in the vaccine industry. Pharmaceutical companies like Pfizer, Johnson & Johnson (J&J), and AstraZeneca (AZ) received Emergency Use Authorizations by the Food and Drug Administration (FDA), as well as full or conditional marketing authorizations in the EU and numerous other countries. A total of 13 vaccines have now been approved across 127 countries.
There is another key player in addition to the pharma and biotech companies that contributed to rapid vaccine development. On this International Clinical Trials Day, let’s turn the spotlight on Clinical Research Organizations (CROs).
CROs are contracted by pharma and biotech companies to perform clinical trials and other clinical development services for drugs, vaccines, and medical devices in order to provide the data necessary for approval by medicine agencies. Many of the COVID-19 vaccines that were developed in the past year were supported by CROs like PRA Health Sciences, ICON, IQVIA, PPD, Parexel, and Covance.
As with many “conventional” drugs, these vaccines could not have made it to market without CROs. My colleagues at PRA’s Center for Vaccines and Emerging Infectious Diseases and across our operational teams worked tirelessly, sacrificing nights, weekends, and time with their families in order to bring these drugs to market.
To fully explain the contribution of my vaccine colleagues across the CRO industry, let me first broadly explain the stages of vaccine development.
This stage is the province of pharmaceutical companies. This stage involves the chemistry and biology necessary to design the vaccine structure. It also involves laying out steps to produce that vaccine to the required standard in commercial quantities, as well as designing clinical trials that satisfy the regulatory stage.
This stage is the province of the medicines agencies, such as the FDA (USA), EMA (Europe), and the MHRA (UK). These agencies set the standards by which vaccines are assessed: how many patients are to be treated, for how long must they be followed up, and what will be considered acceptable efficacy?
This stage is usually the longest part of most development programs—even eight to ten years is not an unusual length. In this stage, specific numbers of patients are required to enroll in trials to test the vaccine in real people. Pharmaceutical companies sometimes run this stage in house, but many outsource this stage to a CRO. Occasionally, we see almost meteoric enrollment of patients. In the 1990s, Pfizer’s Viagra® recruited at an almost unprecedented rate. The public, or a section of it, were truly interested in a novel drug which for the first time could treat their condition. A decade later, the same was true for the various HIV treatments that emerged. Now, in the 2020s, it has happened again for COVID-19.
The conduct and execution of clinical trials has increasingly become the province of CROs. These organizations largely mirror the infrastructure within pharmaceutical companies, with departments dedicated to project management, clinical operations, regulatory affairs, pharmacovigilance, and many others. And they focus largely on the execution stage of development. They are staffed by scientists and physicians who are as well-qualified as their pharma industry counterparts—often with broader experience.
Most CROs do not have the drug discovery or commercial functions of the pharma industry, but they more than make up for it in the execution stage. That is where the size and scope of the clinical operations and regulatory functions plays a pivotal role. “Big CROs” each employ 10,000-25,000 staff in such roles— substantially more than “big pharma”—and they are how these large COVID-19 vaccine trials were executed so rapidly without any loss of safety or quality. “Big CRO” operational staff are located in upwards of 40 countries. These staff interact with participating hospitals and medical offices, answer the inevitable questions from physicians and nurses at the sites, ensure data are collected properly, and send blood samples to labs for analysis. Without CRO staff, these trials simply would not have worked.
So why are CRO names not alongside Pfizer, J&J, AZ, etc.? The relationships between pharmaceutical companies and CROs are generally kept confidential. CROs are permitted to make known their support for a development program only with the express permission of the pharmaceutical company. Pharmaceutical companies rarely publicly acknowledge the role CROs play in their clinical development programs. However, the press has uncharacteristically carried a few articles this year naming ICON, IQVIA and PPD as CROs involved in COVID development programs. A search of the ClinTrial.gov database reveals that the others in the CRO “big 6” (PRA Health Sciences, Parexel, Covance) are also extensively involved in these efforts. Indeed, a survey conducted by the European CRO Federation (EUCROF) indicated that 53 CROs in Europe were involved in COVID-19 clinical trials of all descriptions (vaccines and treatments). 1
The teams at these CROs dedicated themselves to ensuring the approved vaccines were safe and effective. Their responsibilities included identifying sites, preparing applications to Ethics Committees, Institutional Review Boards, and regulatory authorities (and answering questions from these bodies), ensuring the data capture systems were working properly, and training site staff on the trial protocol (all protocols differ). They also checked the data to be sure they were collected properly, corrected any discrepancies or inaccuracies, followed up on any adverse events to ensure they were properly investigated and understood, and finalized the database. All of these strategies demonstrated to the medicines agencies that these vaccines were indeed effective.
Drug development takes the collective experience and expertise of many people, as well as many tried and tested processes. To some, the vaccine development timeline seems rapid. Behind that rush, however, was decades of best practices, experience, expertise, and dedication from thousands of people.
I urge you to receive your vaccination when you are eligible. I extend a heartfelt thank you to my colleagues across the industry who contributed to the rapid successes of the COVID-19 vaccines.
1. Mariangela Lupo , M., Akuffo, E., Lettieri , M., Bonifazi , D., Marini, S. Dehlinger-Kremer, M. (2021). The Current Status of European Research Related to COVID-19: The EUCROF Perspective. Applied Clinical Trials, January 25, 2021. Available at https://www.appliedclinicaltrialsonline.com/view/the-current-status-of-european-research-related-to-covid-19-the-eucrof-perspective
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