Methods

We initially participated in online discussions and agreed to the format of the final 19 questions and their respective answer options. The multiple-choice questions were then converted into an online Google form. The link to this Google form was then forwarded through WhatsApp discussion groups involving oncologists. The online survey was open for 24h on March 27, 2020. The replies received were downloaded as an Excel sheet. Unique E-mail addresses of responders were used to confirm that there were no duplicate entries. Thereafter, we tabulated and analyzed the results limited to those responders who had at least one ongoing clinical trial.

Results

Over a 24-h period, a total of 60 oncologists responded to the survey. This was on the day that the global COVID-19-positive cases were just under 600,000.[1] Of these, 20 did not have an open ongoing clinical trial [[Table 1], Q1. Hence, the results represent the 40 responders who had active ongoing clinical trials and met this sole inclusion criterion. Incidentally, all of them were involved in trials whose objective(s) were unrelated to COVID-19 [[Table 1], Q2.

Table 1 Replies to the 19 multiple-choice question online survey among oncologists

Screening and recruitment [[Table 1], Q3 and Q4]: The majority of sites had stopped screening (22/40, 55%) and recruitment (25/40, 62.5%). About one-third (15/40, 37.5%) were still screening and recruiting. Three centers were not sure.

Staffing and space [[Table 1], Q5]: The sites were almost equally divided among those who still had adequate staff and space to look after trial patients (18/40, 45%) and those who did not (19/40, 47.5%). Once more, three sites were not sure.

Patient concerns about COVID-19 pandemic [[Table 1], Q6–8]: The majority of sites (33/40, 82.5%) made it a point to discuss additional risk related to COVID-19, even though it was not part of the approved informed consent. On their own, patients asked questions regarding their concerns about the COVID-19 pandemic in 35/40 (87.5%) centers. A total of 3 (7.5%) centers had patients who withdrew consent/discontinue on the trial due to COVID-19 fears. Another 8 (20%) centers had documented withdrawal of consent by their patients, where the reason was not disclosed. This gives a total of 11/40 (27.5%) sites who had one or more patients withdrawing consent.

Protocol compliance and deviations [[Table 1], Q9–12]: Difficulties in adherence to scheduling and compliance were faced by 35/40 (87.5%) sites. So also, challenges in performing timely trial-related investigation were reported by 31/40 (77.5%) sites. Problems with providing investigational product (IP) were faced by 17/40 (42.5%) centers. A total of 22/40 (55%) centers had already incorporated the option of virtual visits in place of in-person visits.

Sponsor/contract research organization (CRO)/EC/IRB communication [[Table 1], Q13–16]: PI/co-PI from 30/40 (75%) had already reached out to their respective sponsors or CROs for clarity regarding their trial during the COVID-19 pandemic. Similarly, 27/40 (67.5%) centers had received communication from their sponsors or CROs. A total of 15/40 (37.5%) sites reported difficulty in reporting serious adverse events (SAEs)/protocol deviations/protocol violations as required by the protocol. While EC/IRB remained functional in 15/40 (37.5%) sites, it was not operational in an equal number (14/40, 35%). At 11/40 (27.5) sites, it was not clear whether the EC/IRB was able to do its activity or not.

Safety data-related adverse events and SAE [[Table 1], Q17–19]: A total of 23/40 (57.5%) sites had developed new standard operating procedures (SOPs) to facilitate adverse event reporting and 26/40 (65%) had done the same for SAE reporting. Admission of patients due to SAE while the COVID-19 pandemic was ongoing was reported by 7/40 (17.5%) sites.

Discussion

A PubMed search using “COVID-19” done on March 28, 2020, revealed 1795 references, which became 3075 references by April 8, 2020, an increase of 71% in the short span of 12 days.[4],[5] This is a reflection of the health-care professionals' commitment and focus on tackling the COVID-19 pandemic. With the number of deaths crossing an astounding figure of more than 80,000, the current unprecedented disaster has impacted all walks of our lives, including ongoing clinical trials. In our study, the first proof was the fact that only about one-third (37.5%) of responding oncology centers continued to screen and recruit new patients [[Table 1].

While research priorities should be and remain focused on prevention, mitigation, or treatment of COVID-19, our responsibility toward other ongoing clinical trials should not be forgotten.[6] One of the challenges that we could identify was regarding the adequacy of sufficient space and staff for trial-related activities. It was a stumbling block in 47.5% of the sites included in this study. Redeployment of medical staff for COVID-19 duties coupled with the inability of the nonmedical staff to reach their place of work due to travel restrictions (e.g., lockdown) results in only a skeletal staff available for clinical trials. In addition, some hospitals may have to redeploy clinical trial space to expand inpatients' capacity. Images of hoards of COVID-19 patients lying in hospital corridors (especially from the USA, Spain, and Italy) confirm this to be a reality.[7],[8],[9]

The majority of sites (33/40, 82.5%) made it a point to discuss additional risk related to COVID-19, even though it was not part of the trial requirement. We believe that this is a very important initiative by the investigators, since evidence was quickly emerging from China (confirmed later from Italy) that cancer patients did poorly if infected with COVID-19.[10] On their own, patients asked questions regarding their COVID-19 pandemic concern in 35/40 (87.5%) centers. A total of 27.5% of centers experience patients withdrawing consent, which is exceedingly high and has not been reported earlier from India.[11] We can only assume that the COVID-19 pandemic was the reason, even if that has not been disclosed formally. These data were generated when the global burden of COVID-19-positive cases was just under 600,000. It has now almost tripled and its impact on withdrawal from trials is also likely to be significant.

It was not surprising that almost all the sites faced difficulties in adherence to trial schedule of events (such as hospital visits, investigations, and administration of IP). In order to reduce deviations, just over half the centers had commenced virtual visits. Now that the Medical Council of India has notified telemedicine guidelines (March 25, 2020), all health-care facilities will be able to connect with their patients remotely and effectively.[12]

Effective lines of communication are key to the success of any project. In this instance, the investigators were more proactive in communicating with the other party (75%) as compared to the trial sponsors/CROs (67.5%). This is to be lauded. In spite of such efforts, some difficulty still existed in complying with mandatory reporting specified in trial protocols. The importance of using alternate pathways and backup options in disasters and emergencies needs further emphasis. Our survey showed that ECs were either nonoperational (35%) or their status not communicated to the investigators (another 27.5%). State- and country-wide lockdowns to tackle the COVID-19 pandemic did test disaster preparedness plans quite severely and showed us that that real-world situations are sometimes quite different from what we have anticipated in the past.

With the COVID-19 pandemic taking the lives of more than 89,000 humans, emphasis is back on safety. We have previously reported on how efforts are ongoing to protect frontline health-care workers in this war.[13] Protecting trial patients also requires timely recognition of and prompt management of adverse events and SAEs. To address this, majority of sites had actually developed new SOPs to identify and report them among their trial patients. It is interesting to note that SAE admissions were required in a significant fraction of trial sites. Segregated access to health-care facilities, identification of COVID-19 status, and admission in appropriate wards are key to the safety of such trial patients. To reduce their risk of contacting COVID-19 infection while in hospital, additional prophylaxis and/or mitigation methods may be required to accelerate recovery and timely discharge from the hospital.

This survey results will help us better understand the challenges faced by clinical trials while fighting the COVID-19 pandemic. Corrective measures will prevent irreparable consequences to the integrity of trial data. Authorities stepping in to help provide guidelines include examples from India, the UK, and the USA.[14],[15],[16],[17]

References

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3. Thornton J. Clinical trials suspended in UK to prioritise covid-19 studies and free up staff. BMJ 2020; 368: m1172
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5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/?term= covid-19. [Last accessed on 2020 Apr 08].
6. McDermott MM, Newman AB. Preserving clinical trial integrity during the coronavirus pandemic. JAMA. 2020. [Ahead of Print]
7. Available from: https://edition.cnn.com/2020/03/30/us/brooklyn-hospital-coronavirus-patients-deaths/index.html. [Last accessed on 2020 Apr 08].
8. Available from: https://fullfact.org/online/video-supposedly-showing-covid-19-patients-st-marys-hospital-london-was-actually-filmed-madrid/. [Last accessed on 2020 Apr 08].
9. Available from: https://www.dailymail.co.uk/video/news/video- 2133646/Video-COVID-19-patients-lining-corridors-crammed-Italian-hospital.html. [Last accessed on 2020 Apr 08].
10. Zhang L, Zhu F, Xie L, Wang C, Wang J, Chen R. et al. Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China. Ann Oncol. 2020. [Ahead of Print]
11. Dabhade S, Pandit P, Tiwari S, Pandit D, Chopra A. Reasons for patient's withdrawal from clinical trials of rheumatoid arthritis in India. J Orthop Allied Sci 2015; 3: 8-11
12. Available from: https://www.mohfw.gov.in/pdf/Telemedicine.pdf. [Last accessed on 2020 Mar 28].
13. Purvish MP, Prashant M, Shweta B, Shyam A, Amol P, Atul B, Ranjit S. Protecting healthcare professionals and workers (other than COVID-19 management facilities) from contamination during COVID-19 pandemic. Indian J Med Sci 2020; 72: 3-4
14. Available from: https://theprint.in/health/modi-govt-allows-pharma-firms-to-tweak-clinical-trial-rules-during-covid-19-lockdown/392437/. [Last accessed on 2020 Apr 08].
15. MHRA. Managing Clinical Trials during Coronavirus (COVID-19); 19 March, 2020. Available from: https://www.gov.uk/guidance/managing-clinical-trials-during-coronavirus-COVID-19. [Last accessed on 2020 Apr 08].
16. FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Pandemic: Guidance for Industry, Investigators, and Institutional Review Boards. US Food and Drug Administration; March, 2020. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-COVID-19-pandemic. [Last accessed on 2020 Apr 08].
17. Available from: https://www.nihr.ac.uk/news/dhsc-issues-guidance-on-the-impact-on-COVID-19-on-research-funded-or-supported-by-nihr/24469. [Last accessed on 2020 Apr 08].
18. Dean NE, Gsell PS, Brookmeyer R, Crawford FW, Donnelly CA, Ellenberg SS. et al. Creating a framework for conducting randomized clinical trials during disease outbreaks. N Engl J Med 2020; 382: 1366-9

Address for correspondence

Publication History

Received: 19 April 2020
Accepted: 26 May 2020
Article published online:
28 June 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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