Anastasia Zaitseva

	Through April to May 2020, OCT Clinical, one of the largest CROs in Europe, had been running a survey among researchers from 61 sites in Russia to get the perspective of an investigator regarding clinical trials during the COVID-19 pandemic. According to the results, 22% sites reported their being on a lockdown, while the remaining 78% get on with clinical research, adapting to the current situation. Most sites that continue operations are those which admit patients with acute pathologies. Despite the challenges that clinical research world has been facing over the past three months, 83% of respondents said that they were able to find effective approaches to communicating with sponsors and CROs, including remote monitoring.

	Almost 70% of the investigators surveyed reported that they had been receiving substantial help and support from CROs and sponsors in a variety of forms: some sponsors arrange transportation (taxi) for patients and their relatives, and doctors visiting patients at their homes (even if this was not initially included in the protocol); while others handle the process of uploading source data to an electronic system for remote monitoring. The most common example of such assistance was supplying of personal protective equipment (respirators, gloves, protective gear, disinfectants, etc.) for patients and personnel members. Some sponsors and CROs have also been assisting the sites with the following: 

		COVID-19 testing including home-based tests;

		Conducting online trainings, lectures and meetings;

	Indeed, 80% of the participating investigators confirmed their participation in regular remote CRA visits organized by the CROs. 

	“The outbreak of the novel coronavirus, without doubt, has increased the workload within most of the research sites. Collaboration with sites under the circumstances is more time and labor consuming for clinical research teams since it takes more time to resolve various issues especially when it is the case of a newly initiated site. But regardless of these challenges, our clinical team manages to get on with our work on projects and keep it effective. CRAs also note that their communication with investigators runs smoothly and all the researchers respond in a timely manner even during times like this with limited face-to-face communication. We have not experienced a single case when an investigator or a site refused to cooperate and provide necessary assistance even given the recent developments,” commented Julia Stepanchuk, a Project Manager at OCT.

	Investigators from the Petrov Research Institute of Oncology of the Ministry of Health of Russia (one of the largest oncology sites in Russia) shared what measures have been introduced at their site to manage the situation caused by the pandemic. Among such steps there were the implementation of the necessary standard operating procedures (SOPs), moving all ongoing clinical trials to the clinical diagnostic department, minimization of the time a patient stays at a preventive care facility, and providing personnel and patients with personal protective equipment. They also ensure that patients are being tested for the COVID-19 and thoroughly examine and interview all of the patients during visits to detect the coronavirus.

	As a result of mutual work of CROs, pharma and research sites, almost half of the sites (48%) among the survey respondents had introduced home visits. Also, every second site confirmed their employing IP delivery to patients’ homes. Only 10% of the centers resorted to the help of third-party companies to collect bio samples at patients’ home and transport them to labs. The remaining 90% do not entrust this activity to third parties and handle this issue on their own. 

	One of the key highlights of the survey results is the fact, that only 3% of the sites had to transfer clinical trials along with patients to another site. In addition, more than 40% of the respondents reported that new studies were being launched at their sites, including COVID-19 trials.

	There is a slight decrease in the number of patients. However, new approaches are also being applied in this direction: remote communication with patients and remote transfer of informed consent forms have been introduced. Only if a patient makes the final decision on joining a clinical trial, is he or she invited to a face-to-face consultation. In order to ensure the safety of a study subject, all screening procedures are performed as quickly as possible.

	Additionally, through its survey OCT Clinical have determined that half of the respondents had turned to electronic solutions for clinical trials within the past three months. Some of them experienced working with EDC (Electronic Data Acquisition System) and ePRO (Electronic Patient Diary) for the first time and admitted their effectiveness under the circumstances.

	“We live in a time when, with the help of digital technologies, we are able to continue working as efficiently as possible. For instance, the role of e-questionnaires plays an important role in assessing the quality of life of a patient. Given the situation with the pandemic, this tool greatly simplifies the task of assessing a patient’s condition and makes it possible to get a more detailed picture for the investigator,” commented Karina Khidishyan, MD, an oncologist and an investigator at the Petrov Research Institute of Oncology of the Ministry of Health of Russia 

	“Many procedures have been subjected to rigorous testing both by CROs and sites. A thorough analysis of the situation and the introduction of necessary adjustments required considerable effort from all parties involved in running a clinical trial. In the foreseeable future all the processes will get back to normal, travel bans will be lifted, logistic processes will be restored, and research sites will resume their work in the regular mode. We must give credit to those companies that have demonstrated the highest level of professionalism under such challenging times and have passed this test successfully. I would also like to note, that OCT Clinical and its ongoing studies have not suffered serious damages managing to keep the situation under control,” said Irina Petrova, MD, Director of Clinical Operations at OCT Clinical.

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Findings from an OCT Clinical survey of researchers from 61 sites in Russia to gain the perspective of an investigator regarding clinical trials during the COVID-19 pandemic. 

Trials During the Pandemic: A CRO's Perspective

	Within just a couple of months, the coronavirus pandemic has brutally shaken many industries and companies, jeopardizing their business operations and threatening their entire existence. Adjustments have become inevitable for the clinical trial industry as well. Key regulating bodies (FDA, EMA, MHRA, Ministry of Health of Russia) have been urging sponsors to cancel any on-site visits. New measures are being introduced in many countries, including Russia, Europe and CIS countries, especially when it comes to the interaction of research centers with CRAs, who are the binding link between sponsors and investigators.

	How to ensure the continuity of coordination of all the decisions made via online tools, compliance with all the GCP requirements and protocols; these and many other questions were addressed by Julia Stepanchuk, a project manager at the OCT Clinical CRO, and Anastasia Zaitseva, the Head of Data Management at Data MATRIX, a member company of the OCT Group. Both experts shared practical techniques and gave detailed comments on each of the highlighted issues.

	Stepanchuk, along with the entire OCT’s clinical team, notes that the sites in all the countries of OCT’s operations (Russia, Ukraine, Georgia, Bulgaria, Latvia, Estonia, Lithuania, Belarus, Moldova, Serbia, Croatia, Spain, the Netherlands) that are not on a lockdown demonstrate high flexibility and willingness to adapt to the new reality. Most of the sites based in Russia that continue admitting and treating patients with acute pathologies are not on a lockdown either. None of the sites refused to participate in remote visits or showed any restraint toward remote interaction with CRAs.

	“It is true, that working with sites under these circumstances is more labor- and resource-consuming for the team,” Stepanchuk said. “When interacting with investigators, it takes more time to resolve various issues, especially when it is a new site. Nevertheless, our team has been very quick to adapt to the new reality and keep working hard to ensure the continuity of studies.”

	Several measures are also being taken regarding the work of the sites. First, it is necessary to select sites that are ready to work remotely, and those that are ready to conduct face-to-face visits and begin patient recruitment in such difficult conditions. In addition, lockdown risks are being included in the management plan, in cases when a site is in an active patient enrollment stage.

	Stepanchuk said, “On our first remote visits we also invited sponsor representatives. This was done to assure a sponsor that the site in question is ready to participate in a proper CRA visit, despite the remote mode.”

	It became clear that the introduction of restrictive measures led to the development of a whole range of measures initiated both by research sites and CROs. First, all project plans have been designed with the consideration of the COVID-19 pandemic. For instance, in accordance with the FDA, EMA, and the Ministry of Health of Russia, about 95% of CRA visits run by OCT Clinical are now carried out remotely. Secondly, CROs and sponsors have been developing clear instructions for conducting remote monitoring visits, while clinical teams are being trained on the specifics of conducting such visits.

	“Each guideline is developed taking into account the specifics of a project and the number of checks that need to be done in each particular case; steps to be done before, during, and after the visit; what tools are required for a CRA to conduct a proper visit (audio, videos, photo),” Stepanchuk explained. “Prior to a visit, CRAs provide investigators with detailed information on what they need to deliver during the visit.”

	In the meantime, the CRAs stress that they have to dedicate more time to such visits, which in the end pays off, because such an approach ensures continuous CRA-investigator communication, and that, in turn, results in faster and more effective resolution of various issues.

	During a monitoring visit, a significant amount of time is taken up by the data verification procedure (Source Data Verification, SDV). This is a rather time-consuming procedure, the main purpose of which is to make sure that all the information entered in a CRF (case report form) matches the data from the source medical records. Also important is that, in the light of the pandemic, it became necessary to modify some of the eCRFs and to increase the time needed for remote data verification and query issues. This makes a day-to-day communication mode between CRAs and sites necessary.

	“Some of the eCRFs, that were not supposed to include information on additional lab tests, are now being modified to include the entry on COVID-19 tests,” Zaitseva explained. “Though we haven’t encountered such cases yet, COVID-19 positive cases will be coded as adverse events, except when it is a COVID-19 trial.”

	Following all the above cases, it becomes obvious that even operating within lockdown and self-isolation, it is possible to ensure the continuity of clinical trials without compromising quality and safety of the involved participants. Also, important to note is that there is a high probability that the situation will make necessary adjustments to the industry, which will be there even after everything is back to normal. It is the task of the clinical research players to stay alert in order to be able to adapt and quickly respond to all the changes, while always being aware of the top priority of clinical research which is to ensure the safety of all involved participants.

COVID-19 response is leading to new measures being introduced in many countries, including Russia, Europe and CIS countries, especially when it comes to the interaction of research centers with CRAs.

Anastasia Zaitseva

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