Şebnem Yaşaroğullari works as VP of clinical operations for Mene Research 

Şebnem Yaşaroğullari

Martine Dehlinger-Kremer, PhD, President, EUCROF and VP Scientific Affairs, Pediatric SME, ICON Plc.

Şebnem Yaşaroğullari, VP, clinical operations, Mene Research

Helena Lüning, study start-up manager, ICON PLC

Clinical research is necessary for the development of new health products. The evaluation of the safety and efficacy of new drugs or devices in patients is already governed by numerous regulations. Furthermore, speed requirements and competition between the various pharmaceutical and biotech companies are also factors in the dynamics of the industry. All these aspects intensified during the outbreak of the COVID-19 pandemic which was an opportunity to exemplify the unique role that Clinical Research Organizations (CROs) play in clinical research due to their expertise and ability to rapidly adapt and respond to a changing environment.

The COVID-19 pandemic had a significant impact on the activity of CROs and many of them had to suspend or delay clinical trials due to the pandemic, as well as the fact that many of their staff were unable to travel to sites due to travel restrictions. This halting led to a reduction of patient enrollments and difficulties for on-site monitoring.

 Additionally, the pandemic caused a disruption in the supply chain for clinical trial materials, as well as the availability of laboratory services, which further complicated the conduct of clinical trials. As a result, many CROs have had to move toward offering virtual services that can be performed remotely, such as patient recruitment, monitoring, data management, and statistical analysis, in order to continue the important work of researching novel and important medicines.

A survey involving the European CRO Federation (EUCROF) was conducted between July and September 2022 with its affiliated CROs in order to determine how the COVID-19 pandemic impacted their clinical research services.

 A total of 52 responses were received and 77% of the participating CROs stated that the COVID-19 pandemic caused changes in their internal organization and 75% reported that this pandemic induced negative impact on their ongoing trials.

The main negative impacts were the discontinuation or slowing down of recruitment of new trial participants (92%), cancellation or postponement of on-site monitoring visits (77%), temporary halt of the trial at some of all trial sites (69%) and cancellation of patient visits as the trial participants cannot reach the site (62%).

 Negative impacts on clinical research encountered in CROs during the COVID-19 pandemic.

David Rolando, biostatistician, Axelys Santé

CROs quickly adapted their services to counter this phenomenon. Telemedicine, which is a form of remote medical practice using information and communication technologies, has been massively deployed in Europe and overall. As an example, in France, 67 studies based on telemedicine and currently recruiting or not yet recruiting are registered on the Clinicaltrials.gov website, making France the

first country in Europe to implement telemedicine massively in its clinical research.

In this survey, the main measures taken to reduce the negative impact of the COVID-19 pandemic were the conversion of physical visits on site into phone or video visits (82%) and extension of the duration of the trial (82%).

The European Medicines Agency published guidelines on “Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic”

; 83% of the respondents of the survey were aware of these guidelines and 97% implemented them. A total of 93% of respondents thought that these guidelines were useful to improve their business in this context.

CROs role in COVID-19 vaccines and treatments

CROs played a critical role in the COVID-19 clinical trial race. They provided expertise in the development of clinical trial protocols, and they helped to ensure that the trials adhered to all local, national, and international regulations. CROs were also responsible for managing the logistics of the trials, including recruitment of sites, patient enrollment, data collection, and data analysis. Finally, CROs were also responsible for the strategy of the development of the new medicines helping biotech companies with limited experience in drug development.

The development of a vaccine against the SARS-CoV-2 in 2020 resulted of an international effort as never seen before. This effort contributed to the development of several vaccine candidates, such as Comirnaty® (Pfizer-BioNTech) and Spikevax® (Moderna), within a year, whereas other vaccines typically took several years to develop in the past.

 This was partly allowed by regulatory authorities (FDA6 and EMA7) who updated their guidelines regarding COVID-19 vaccine development to facilitate the regulatory processes during the pandemic, but also by the rapidity of CROs in proposing services of clinical research and drug development expertise to pharmaceutical companies. Indeed, CROs have played a critical role in the execution of vaccine studies for COVID-19, providing clinical trial support services, such as site selection, sample collection, and data management. CROs have enabled vaccine developers to quickly initiate and execute clinical trials, helping to accelerate the development of vaccines and drugs such as remdesivir. CROs have also helped coordinate global clinical trials, allowing for the timely collection of data from different countries and completion of clinical trials.

In the survey cited above, 65% of CROs reported to have participated in COVID-19 trials in 2020–2022 and almost a majority participated to two studies (41%; n=5–10 studies for 21% and >10 for 29%). Most of these studies included more than 100 patients.

Number of patients/participants in COVID-19 studies managed by CROs in 2020–2022.

Most of these studies were large studies, involving thousands of participants and were essentially drug (59%) and vaccine (53%) COVID-19 studies (

). About half of the CROs participated in vaccine studies (one or two studies in majority, involving hundreds of patients). The vast majority of these studies were performed in Europe.

Types of studies on COVID-19 performed by CROs in 2020–2022 (more than one answer possible).

Despite the COVID-19 crisis, CROs have been able to be innovative to avoid disruption in clinical research and therefore they played an important role in the development of COVID-19 vaccines studies. Thus, 69% of the CROs surveyed in the cited EUCROF survey have implemented new digital tools (e.g., telemedicine, remote monitoring) within the context of the COVID-19 pandemic and they all consider they will keep them once the pandemic is over. A total of 35% of CROs conducted more than 50% of their monitoring visits remotely. Even though CROs have used new digital tools, they generally (83%) did not actively participate in the development of health mobile applications.

CROs were heavily involved in COVID studies, but for 70% of those surveyed in the EUCROF survey, this activity represented less than 10% of their business. They considered that the biggest challenges during COVID-19 pandemic was set-up, conduct and follow-up of clinical studies (e.g., recruitment, data collection (77%), business development, interactions with partners and clients (44%) and development/adaptation to new working tools e.g. videoconference, remote monitoring (34%)).

CROs are essential in providing the necessary expertise, resources and support to carry out clinical research and bring new drugs to market. CROs can help improve quality, create efficiencies and reduce timelines, making them an invaluable part of the drug development process. The COVID-19 pandemic allowed CROs to show flexibility and innovation despite physical obstacles. They were able to maintain the ongoing clinical research in particular by using new technologies in a shortened timeframe to meet an urgent public health demand. CROs have been a key contributor to the development of new medicines in a very short period of time during the COVID-19 pandemic. Their ability to be agile and drive innovation will position them as the trusted partner for drug development as the clinical research industry continues to evolve.

1. Tuttle KR. Impact of the COVID-19 pandemic on clinical research. Nat Rev Nephrol. 2020;16:562-4.

2. Sathian B, Asim M, Banerjee I, et al. Impact of COVID-19 on clinical trials and clinical research: A systematic review. Nepal J Epidemiol. 2020;10:878-87.

3. Harrison F, Coladangelo, Heutte M, Hardman TC, Marini S (2022). Impact of the COVID-19 Pandemic on Clinical Trial Conduct: Lessons for the Future [Preprint]. doi:10.21203/rs.3.rs-1118410/v1.

4. La France est le pays européen avec le plus d’essais cliniques en télémédecine. Télémédecine 360. Published July 28, 2015. Accessed June 1, 2022. 

https://www.telemedecine-360.com/la-france-est-le-pays-europeen-avec-le-plus-dessais-cliniques-de-telemedecine/

5. European Medicines Agency. Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic. Version 5 10/02/2022. 

https://health.ec.europa.eu/system/files/2022-02/guidanceclinicaltrials_covid19_en_1.pdf

6. Wibawa T. COVID-19 vaccine research and development: ethical issues. Trop Med Int Health. 2021;26:14-9.

7. Food Drug Administration. COVID-19 Vaccines.Published online May 27, 2022. Accessed June 1, 2022. 

https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines

8. European Medicines Agency. COVID-19 vaccines: development, evaluation, approval and monitoring. European Medicines Agency. Published October 27, 2020. Accessed June 1, 2022. 

https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/vaccines-covid-19/covid-19-vaccines-development-evaluation-approval-monitoring

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