Donato Bonifazi

The COVID-19 pandemic has affected different countries in different ways, but across the world it has had three common, defining characteristics: speed and scale (i.e., the disease spread quickly with potential to overwhelm the country's health systems); severity (an estimated 20% of cases are severe or critical, with increased risk in older age groups or those with underlying conditions); societal and economic disruption (particularly regarding shocks to healthcare systems and measures taken to control transmission.)

 Clinical research plays a crucial role in developing diagnostics and medicines to fight the ongoing COVID-19 pandemic, through rapid and accurate clinical trials, and collect robust and reliable outcomes, in a variety of different settings, on a large scale. Intensive global research collaborations among all stakeholders and industry involving all countries are necessary to enable identification and testing of effective treatments, vaccines and diagnostics.

The European CRO Federation, EUCROF, is a non-profit entity founded in 2005 and representing the interests of Contract-Clinical Research Organizations (CROs) in Europe towards regulatory bodies, the bio-pharmaceutical and medical device industry, healthcare professionals and patient’s associations. The Federation consists of Members (National CRO associations) from 12 countries, including Belgium with BeCRO, Czech Republic with ACRO-CZ, France with AFCROs, Germany with BVMA, Greece with HACRO, Italy with AICRO, the Netherlands with ACRON, Romania with ACCSCR, Slovakia with SACROP, Spain with AECIC, Turkey with SAKDER, UK with CCRA, and 15 Associate Members based in Albania, Austria, Bulgaria, Croatia, Denmark, Georgia, Serbia, Spain, Sweden, Switzerland (2), Ukraine (2), United Kingdom (2) as well as three Partner Members based outside Europe, in Algeria, Egypt and Israel. EUCROF is intensively engaged with its members and other involved stakeholders in the conduct of COVID-19 related clinical research. Through its large Network, represented by over 385 affiliated member-CROs and 25 countries, EUCROF contributes to have a wide perspective on the impact COVID-19 pandemic has having on ongoing and upcoming Clinical Trials.

The article provides the results of a brief survey conducted by the European CRO Federation (EUCROF) with the goal of collating data focused on COVID-19 research activities of its members. The survey was sent to all affiliated member-CROs to obtain an overview of the extent of contribution of EUCROF members to COVID-19 relatedresearch, and to collect information on pandemic impact on CTs, measuring the active participation to research activities planned to face coronavirus outbreak.

The online quick survey was developed through Google Forms and was distributed by email to all affiliated members-CROs, in March 2020. The survey included the following questions regarding the CROs' research activities:

Has your company been approached to participate in any research activities associated with COVID-19?

If yes, is your company actively participating in research activities now and scheduled to do so in the next 3 to 6 months?

Are the services provided on a national or international level?

If yes to either, please specify what activities you will be contributing to the research? Services provided by the CRO (tick all that apply)

Questions 1-2 of the survey were aimed to understand whether the pandemic had an impact on the clinical studies management activities, and if so, question 3 investigated to what extent the EUCROF affiliated member-CROs were to be involved in the next future (3-6 months). Questions 4 and 5 were aimed to qualify whether and how many respondents provided services at national or international level, and if respondent CROs were national or multinational. Finally, question 6 investigated which services were more frequently provided.

Results were collected from March 2020 to May 2020, analyzed electronically through Google Forms statistics and exported into graphs using Excel.

In total, 68 responses to the survey were received from affiliated member-CROs and analyzed electronically. The analysis of the results shows that 53 out of 68 of the respondent CROs (78%, as shown in Figure 1) were involved in COVID-19-related research activities, of which 48 (91%) expect to maintain and continue with this research for at least further 3-6 months.

respondent CROs who positively declared to be

Graph 1 describes globally the number of the single ongoing research activity associated with COVID-19 performed by the CROs and in detail if it involves only a potential therapeutic, and/or a vaccine, and/or a diagnostic or altogether the three research activities, Table 1 describes both the number and the percentage of each research activity.

In total 42 out of 53 (79%) respondent CROs are focusing their current research activities on a potential therapeutic, 24 (45%) on testing vaccines and 14 (26%) on testing diagnostics.

In details, the respondents who declared to be involved only in research activities on potential therapeutic are 19 (36%), while those who are involved only in research activities on vaccine and diagnostic are respectively 2 (4%) and 4 (8%). Furthermore, we analyzed the different combination of research areas and it resulted that the number of CROs whose research activities involved both in a potential therapeutic and a vaccine are 15 (28%); research activities involving both a vaccine and a diagnostic are 2 (4%); research activities involving both a potential therapeutic and a diagnostic are 3 (6%). The respondent CROs who are involved in all the three areas of research are 5 (9%).

As illustrated in Graph 2, the survey results show that 76% (52 out of 68) of the respondent CROs provide international services, whereas 24% (16 out of 68) provide national services. Regarding their legal forms, 65% (44 out of 68) are multinational CRO, whereas 35% (24 out of 68) are national CROs. We also analyzed the number of national CROs which provided services at International level, and these are 14 out of 24, while the number of national CROs which provide services locally is 10 out of 24. The multinational CROs who provide services at national or International level are respectively 6 and 38 out of 44.

Graph 3 and 4 in details illustrate the number of International and National services provided by respondent CROs involved in COVID-19 research, as well as whether they are national or International. Moreover, table 2 describes that 12 (23%) National CROs involved in COVID-19 research provide International services, whereas 8 (15%) provide national services; 6 (11%) multinational CROs likewise involved in coronavirus research activities declared to provide national services, while 27 (51%) answered to provide International services.

With reference to the type of services provided by the respondent CROs and the kind of activities they are or will be contributing to in the research on COVID-19, 69% (47 out of 68) declared to be involved in Clinical Monitoring, 68% (46 out of 68) in Project Management, 63% (43 out of 68) in Data Management, 54% (37 out of 68) in Regulatory Affairs, 54% (37 out of 68) in Statistics and 53% (36 out of 68) in Medical Writing. In detail, considering only the 53 CROs involved in COVID-19 research activities, we found that 40 out of 53 (75%) are mainly involved in Clinical Monitoring, 41 (77%) in Project Management and 37 (70%) in Data Management. Also, 32 CROs out of 53 (60%) are involved in Regulatory Affairs, 33 (62%) in Statistics, 32 (60%) in Medical Writing.

Answers to questions 3a, 3b and 3c are considered in total, as single choice and in combination. They are reported as numbers and in percentages (out of the Total of 53 CROs involved in COIVID-19 Research).

. Answers to questions 3a, 3b and 3c. The participation in research on potential therapeutic, vaccine and diagnostic is provided by all combinations among research activities. On the left Y-axis, it is reported the number of positive responses calculated on the total number of CROs participating in COVID-19 research.

. Answers from questions 4 to 5. Graph 2 describes the number of CROs providing National or International services, the National or Multinational CROs and National CROs proving International Services, out of a total of 68 CROs respondents.

Graph 3 describes the total number of National and International services provided by the respondent CROs which are involved in COVID-19 research. Graph 4 describes the total number of National and Multinational EUCROF CROs, involved in COVID-19 research

National and international CROs, involved in COVID-19 research, providing International or national services were counted.

The survey has been successful in identifying among the respondents how many EUCROF affiliated members-CROs are involved in research related to COVID-19 and are at the forefront of the fight against this challenging pandemic. It is envisaged that EUCROF, through its affiliated members-CROs, and other researchers, would continue to work together to accelerate research activities related to COVID-19 and diagnostics. Leveraging tools, resources and knowledge would give the greatest chance of success against this difficult threat and provide an opportunity for collaborative (rather than competitive) clinical research in a way that is unprecedented. The opportunity of surveys and the dissemination of their data at European and pan-European level is intended to contribute to build large datasets. The potential integration of these large datasets would result in valuable insights to help tackle any subsequent SARS-COV-2 like outbreaks. The impact of COVID-19 on day-to-day activities as well as on the health of people across the world and the global economy is considerable enough to have evidently warranted coordinated and focused initiatives to circulate and share knowledge and expertise. Examples of this are represented by the nationally targeted effort, UK Coronavirus Immunology Consortium (UK-CIC),

 intended to understand immune responses to the virus SARS-CoV-2 that causes Covid-19 and to tackle some key questions and deliver real benefits to patients and public health. The UK-CIC focuses on five key research themes: 

, to characterize the primary immune response to COVID-19 and how this relates to clinical outcome of individual patients; 

, to identify how effective immunity is established and maintained to prevent re-infection; 

 to understand how the immune system can damage tissue while fighting COVID-19 and how this can be stopped; 

 to examine if immunity to other mild ‘seasonal’ coronaviruses (that cause common colds) can alter the outcome of SARS-CoV-2 infection; and 

 to reveal how SARS-CoV-2 can ‘evade’ the immune system. Also, innovation hubs such as NESTA

 are mobilizing collective intelligence to face the COVID-19 threat. NESTA promotes the exploitation of collective intelligence to predict, monitor, and find solutions to the COVID-19 pandemic. For instance, responding to concerns about lack of access to testing for COVID-19, Nesta Collective Intelligence grantee 

 is behind an effort to develop a cheap, quick coronavirus test to be possibly used anywhere in the world. The initiative is crowdsourcing ideas from Do-It-Yourself biology communities,

 with the ambition to open source and share designs so that certified labs can easily produce test kits for their communities.

This pandemic also represents an example of increased collaboration among industry and authorities such as the European Commission and the European Medicines Agency (EMA), where an easing of competition rules and flexibility shown by authorities has helped pharmaceutical companies and medical device manufacturers, cooperate to overcome problems that threaten the security of supply of vital medicines and equipment during the COVID-19 pandemic.

EMA has established dedicated task forces to deal with the scientific, regulatory and operational challenges created by the COVID-19 pandemic and initiated its business continuity plan. The COVID-19 EMA pandemic Task Force (COVID-ETF) has the role to help EU Member States and the European Commission to take quick and coordinated regulatory actions on the development, authorization and safety monitoring of medicines and vaccines intended for the treatment and prevention of COVID-19.

Moreover, the European Commission proposed a new Pharmaceutical Strategy for Europe which has been largely fostered by the crisis Europe is facing also due to the coronavirus pandemic. It has been acknowledged that 

the unprecedented coronavirus pandemic further demonstrated how important it is to have a crisis-resistant system and ensure availability of medicines under all circumstance.

 The Pharmaceutical Strategy for Europe aims to fulfil unmet needs and ensure accessibility and affordability for patients and health systems sustainability. Therefore, the strategy will establish a future proof of regulatory framework and support industry in promoting research and technologies that actually reach patients and fulfil their therapeutic needs while addressing market failures.

Due to the current pandemic, EUCROF is also developing a second survey to be submitted to all its affiliated members, aimed at collecting information on the economic impact the coronavirus pandemic is causing on CROs research activities and Clinical Trials.

In summary, our data reveal that the majority of EUCROF affiliated member-CROs responders to the survey are dedicated to supporting clinical research activities aimed at developing effective and safe medicines, vaccines, and diagnostics for COVID-19. Since the pandemic outbreak, European clinical research has aimed to address challenges from the SARS-CoV-2 infection and disease, and many innovative initiatives, involving industry, academia, policy makers, patient associations and society at large, have been started with the intention, of delivering useful and effective solutions to face this and possible future pandemics. Our findings show how promptly the respondent CROs have oriented towards research activities to fulfil the current needs which have arisen from the COVID-19 pandemic. Successful collaborations between Pharma/Biotech/Device industry and CRO'S, as well as the ability to leverage knowledge and resources between all of them, will play a key role in an effective and efficacious fight against the global COVID-19 pandemic and are desperately needed in order to overcome such a tremendous challenge. Projecting the preliminary results of this survey on a larger scale, we may deduct how constructively critical is the role of CROs in implementing research projects in every field the community may identify as strategic for the rising needs, particularly in difficult times when the maximal flexibility and a fast reaction represent a substantial requirement.

, MSc, EUCROF Communication Working Group;

, EUCROF Associate Member, Richmond Pharmacology Ltd;

, PharmD, EUCROF Code of Conduct Task Force;

, MEcon, EUCROF Events and Training Working Group Chair;

WHO COVID-19 preparedness and response progress report 1 FEBRUARY TO 30 JUNE 2020.

Nesta tackles the COVID-19 threat; https://www.nesta.org.uk/blog/mobilising-collective-intelligence-tackle-coronavirus-threat/. accessed 07 Oct 2020

Do-It-yourself biology; https://diybio.org/

Landrain T, Meyer M, Perez AM, Sussan R. Do-it-yourself biology: challenges and promises for an open science and technology movement. 

. 2013;7(3):115-126. doi:10.1007/s11693-013-9116-4

COVID-19 EMA pandemic Task Force; https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/emas-governance-during-covid-19-pandemic

https://ec.europa.eu/health/human-use/strategy_en

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