Longitudinal Experience With and Impressions of COVID-19–Related Clinical Research Changes

PURPOSE:

The COVID-19 pandemic has led to profound changes in clinical research, including remote consent, telehealth, off-site procedures, shipment of therapy, and remote study monitoring. We assessed longitudinal perceptions of these adjustments among clinical research professionals.

METHODS:

We distributed an anonymous survey assessing experiences, perceptions, and recommendations regarding COVID-19–related clinical research adjustments to cancer clinical research office personnel in May 2020 and again in November 2020. Responses were compared using Fisher's exact and Mann-Whitney U tests.

RESULTS:

A total of 90 of 102 invited research personnel (88%) responded. Fifty-three (59%) reported participating in both initial and follow-up surveys. The proportion of respondents reporting personal experience with COVID-19–related adjustments increased over time, particularly for remote initial consent (29% v 4%), remote reconsent (24% v 9%), and remote study monitoring (36% v 22%). Perceived impact of COVID-19–related adjustments on data quality (P = .02) and patient experience (P = .002) improved significantly. However, perceived effect on patient safety (P = .02) and respondent's experience (P = .09) became less favorable. Individuals with personal experience with the adjustment were more likely to recommend continuing remote consent (62% v 38%; P = .04), remote monitoring (69% v 45%; P = .05), and therapy shipment (67% v 35%; P = .01) after the COVID-19 pandemic, with nonsignificant trends for off-site diagnostics (44% v 24%; P = .13) and telehealth visits (66% v 45%; P = .08).

CONCLUSION:

More than 6 months into the global pandemic, perceptions of COVID-19–related clinical research changes remain favorable. Experienced individuals are more likely to recommend that these changes continue in the future.

INTRODUCTION

The COVID-19 pandemic has posed numerous and unprecedented challenges to clinical research, including site closures, travel restrictions, quarantines, limited or delayed investigational product availability, and staff and patient infections.^1-3 Recognizing that such occurrences may hinder and complicate meeting protocol requirements, regulatory authorities such as the US Food and Drug Administration (FDA) and National Institutes of Health (NIH) have issued guidance on possible adjustments to conventional clinical research practices.^4,5 These include consideration of telephone or video visits; performance of laboratory tests, imaging studies, and even treatment administration at local rather than central study sites; delaying certain assessments; remote informed consent; shipping oral study therapy to patients' homes; and remote monitoring.

In this way, the COVID-19 pandemic has reversed a decades-long trend of cancer clinical trials becoming more complex and rigid.^6,7 Indeed, organizations representing patients, clinicians, investigators, sponsors, and regulatory authorities have long advocated for greater flexibility in cancer clinical trial design and conduct, which in turn may increase access to trials, decrease demands on trial participants, and improve trial enrollment, completion, and result generalizability.^8-10

To assess the perceived impact of COVID-19–related clinical trial adjustments, approximately 1 month into pandemic clinical trial operations, we distributed a survey to clinical research professionals at a National Cancer Institute (NCI)-designated comprehensive cancer center.¹¹ We targeted these individuals because of their familiarity with protocol requirements and contact with patients, investigators, sponsors, and regulatory agencies.^12,13 Because the initial survey was conducted at the outset of the COVID-19 pandemic, we reassessed reactions to COVID-19–related clinical trial adjustments 6 months later.

METHODS

Study Setting

The NCI-designated Harold C. Simmons Comprehensive Cancer Center in Dallas, Texas, conducts clinical trials at a primary university clinic site, two satellite clinic sites, and at affiliate sites of Parkland Health and Hospital System (the safety-net medical provider for Dallas County) and Children's Health Dallas. The Simmons Clinical Research Office employs a staff of more than 100, including nurses, coordinators, managers, and regulatory personnel.

In March 2020, in response to the emerging COVID-19 pandemic and an institutional stay-at-home order, the Simmons Clinical Research Office placed new enrollments to clinical trials on hold. However, patients previously enrolled were continued on study and those who had already signed consent for study participation were allowed to be considered for enrollment if deemed in their best interest to continue by the treating clinician. Adjustments covered in FDA and NIH guidance, including remote consent, telehealth visits, shipment of oral study therapy to patients' homes, and remote monitoring were instituted. In April 2020, therapeutic clinical trials were reopened to enrollment in a staged fashion, with almost all trials reopened by June.

Survey Design and Administration

In late May 2020, study authors (D.E.G. and E.L.W.) delivered a webinar reviewing FDA- and NIH-based COVID-19–related clinical research adjustments to Clinical Research Office staff involved in adult cancer clinical trials. Personnel involved exclusively in pediatric cancer clinical trials were not included in this study because at our center, these studies (which are predominantly conducted in the inpatient setting) were not substantially affected by these changes. Immediately after this session, we distributed an anonymous survey to these individuals via e-mail. Two electronic reminders were sent before the survey was closed 1 week later. In late November 2020 (6 months after the initial survey), we redistributed the survey, again sending two electronic reminders before closing the survey 1 week later. The November survey was identical to the May survey with the exception of addition of a single question asking participants if they recalled participating in the earlier survey. The survey was designed by study authors with expertise in clinical oncology (D.E.G. and M.S.B.), clinical trial design and implementation (D.E.G., M.S.B., and E.L.W.), survey administration (V.L.C.), and survey methodology (S.J.C.L.). Survey questions are shown in the Data Supplement (online only). Survey data were collected and managed using REDCap electronic data capture tools.¹⁴

The survey was exempt from institutional review board review and did not require written, informed consent from respondents for the following reasons: following Office of Human Research Protection Program changes to the Common Rule, surveys are no longer considered human subjects research; we did not engage protected health information to identify eligible participants; the survey was voluntary, and individuals could decline to participate simply by not completing the survey; and survey responses were not linked to individual identities.

Statistical Analysis

Mean survey response scores were computed by assigning a point scale ranging from –4 (Negative—A lot) to +4 (Positive—A lot) for the survey questions about impact of COVID-19–related clinical trial adjustments and from –3 (Much worse) to +3 (Much better) for survey questions about perceptions of specific COVID-19 adjustments, then taking the mean of those scores, ignoring unsure or no opinion responses. Whether a respondent had experience with a given adjustment was determined using the answers to a Types of COVID-19–related clinical trial adjustments experienced survey question (Appendix Table A1, online only). Those with experience with either remote initial consent or remote reconsent were counted as having experience with remote consent. P values for adjustment continuance were computed by applying Fisher's exact test to the compared contingency tables. Because the survey was distributed anonymously, no paired comparison analysis was conducted for individual respondents. P values for perceived adjustment impacts were computed by performing a two-sided Mann-Whitney U test on the same set of point scores used to compute mean scores.

RESULTS

Among 102 Clinical Research Office personnel invited to participate, 90 (88%) completed the survey. Of these individuals, 53 (59%) reported having completed the earlier survey distributed 6 months earlier, 15 (17%) did not recall, 21 (23%) reported not participating, and 1 (1%) did not answer. Respondent characteristics are shown in the Data Supplement. Reflecting the diverse responsibilities of a major clinical research operation and the high response rate, respondents held a variety of positions across a variety of disease-related groups. The most common positions were research coordinator (26%), administrative manager (13%), and clinical manager (12%). More than one quarter of respondents had positions that do not typically involve patient-facing activities but do entail experience with other trial considerations such as data quality and study monitoring, including administrative manager (13%), quality assurance or education (6%), finance (4%), and regulatory coordinator (3%). Fifty-three percent of respondents had more than 5 years' experience in the field of clinical research.

Compared to the initial survey, a larger proportion of respondents reported experience with multiple COVID-19–related adjustments to clinical trials in the follow-up survey (Data Supplement). At the time of the follow-up survey, 38% of respondents were actively following trial patients enrolled during COVID-19, with 16% following more than five patients. By contrast, at the time of the initial survey, only 14% of respondents were actively following trial patients enrolled during COVID-19 (2% following more than five patients). Similarly, experience with specific COVID-19–related trial adjustments also increased, particularly for remote initial consent (from 4% to 29%) and remote reconsent (from 9% to 24%). Notably, off-site treatment administration remained an extremely rare event, with reported personal experience remaining under 5% (1% and 3% at initial and follow-up surveys, respectively).

Recognizing the clear limitations of asking clinical research personnel to assess reactions of other individuals, we asked respondents to describe their own, patients', and clinicians' perceptions of COVID-19–related clinical research adjustments (Fig 1). In general, mean values for almost all perceptions were either neutral or positive (ie, score ≥ 0). Overall, recent perceptions tended to be more favorable than initial perceptions, but these differences did not reach statistical significance (P = .17). As a surrogate marker of exposure to clinical research considerations during the COVID-19 pandemic, we also compared responses among individuals who reported also participating in the initial survey versus those for whom the recent survey was their first (Data Supplement). In general, the group that reported participating in the initial survey reported a more favorable overall impression of COVID-19–related clinical research adjustments (P = .003), with significant differences noted for reported patient perception of remote consent (P = .001) and patient perception of telehealth (P = .05).

FIG 1.

Perceptions of COVID-19–related clinical research adjustments at 1-month and 7-month timepoints. Blue bars = respondent perception; red bars = reported patient perception; teal bars = reported clinician perception. Mean overall perception at 1 month, 0.7; mean overall perception at 7 months, 0.9 (P = .17). Remote consent: (A) 1-month survey and (B) 7-month survey. Respondent perception: P = .29. Reported patient perception: P = .82. Reported clinician perception: P = .56. Telehealth: (C) 1-month survey and (D) 7-month survey. Respondent perception: P = .72. Reported patient perception: P = .91. Reported clinician perception: P = .16. Therapy shipment: (E) 1-month survey and (F) 7-month survey. Respondent perception: P = .67. Reported patient perception: P = .39. Reported clinician perception: P = .10. Off-site diagnostic procedures: (G) 1-month survey and (H) 7-month survey. Respondent perception: P = .14. Reported patient perception: P = .65. Reported clinician perception: P = .26. Off-site treatment administration: (I) 1-month survey and (J) 7-month survey. Respondent perception: P = .31. Reported patient perception: P = .65. Reported clinician perception: P = .27. Remote monitoring: (K) 1-month survey and (L) 7-month survey. Respondent perception: P = .26. Reported patient perception: P = .51. Reported clinician perception: P = .24.

We also assessed differences over time in the perceived impact of COVID-19–related clinical research adjustments on various aspects of clinical research practice (Fig 2). All perceptions had a mean value either neutral or positive (ie, score ≥ 0). Perceived impact on treatment efficacy, data quality, patient experience, clinician or investigator communication, and sponsor or monitor communication all improved, with significant differences for data quality and patient experience. Conversely, perceived impact on patient communication, patient safety, and respondents' own experience became less favorable, with significant differences for patient safety.

FIG 2.

Perceived impact of COVID-19–related clinical trial adjustments at 1-month and 7-month timepoints. Blue bars = 1-month survey; red bars = 7-month survey. (A) Patient safety (P = .02). (B) Treatment efficacy (P = .77). (C) Data quality (P = .02). (D) Patient experience (P = .002). (E) Patient communication (P = .58). (F) Clinician or investigator communication (P = .41). (G) Sponsor or monitor communication (P = .24). (H) Respondent experience (P = .09).

Although we observed clear support for sustaining COVID-19–related clinical research adjustments beyond the pandemic, enthusiasm did not increase over time, with 31% considering it very important (v 34% initially), 10% considering it pretty important (v 15% initially), 14% considering it important (v 14% initially), 9% considering it somewhat important (v 6% initially), and 36% not answering (v 31% initially). Support for continuing specific adjustments after the COVID-19 pandemic ends is shown in Table 1. Although the proportion of individuals recommending practice continuation increased numerically for all adjustments between the initial and follow-up surveys, these differences were not statistically significant. We also examined recommendations to continue COVID-19–related clinical research adjustments according to respondent experience (Appendix Table A1, online only). With the exception of off-site treatment, more experienced individuals (defined as either personal experience with a specific adjustment or years in the clinical research profession) were more likely to recommend continuing these adjustments. These differences reached statistical significance for remote consent (62% v 38%, P = .04), remote monitoring (69% v 45%, P = .05), and therapy shipment (67% v 35%, P = .01). Despite these trends, only a minority of respondents supported a number of adjustments. For both Table 1 and Appendix Table A1, this observation may reflect the design of these survey questions, for which a not checked response could signify a belief that an adjustment should not be continued, or a preference not to answer the particular question.

TABLE 1.

Proportion of Respondents Recommending to Continue COVID-19–Related Clinical Research Adjustments in the Future

DISCUSSION

The COVID-19 pandemic offers an unprecedented opportunity to evaluate major shifts in clinical research practice, including flexibility in timing and location of study treatment and procedures, shipping therapy directly to patients' homes, telehealth-based consenting and study visits, and remote study monitoring.¹⁵ In this study, we assessed longitudinal reactions to these adjustments among a large group of clinical research professionals. Through surveys administered one and 7 months into this public health emergency, we evaluated respondents' experience, perceptions, and recommendations.

During the 6 months between surveys, we found that clinical research personnel gained greater direct experience with COVID-19–related clinical trial adjustments, particularly for remote consenting and remote study monitoring. Off-site treatment administration remained rare, reported by fewer than 5% of respondents in both May and November 2020. At both time points, clinical research professionals reported that their own, patients', and clinicians' impressions of COVID-19–related adjustments were generally favorable. In particular, respondents felt that patients welcomed adjustments increasing the convenience of trial participation, such as telehealth visits, shipment of oral study therapy to their homes, off-site diagnostic procedures, and off-site treatment administration. This observation echoes growing interest in decentralized clinical trials, in which patients may gain access to promising experimental therapies without frequent travel to distant trial sites.¹⁶

Those with more exposure to COVID-19–related clinical trial adjustments generally viewed their effects on clinical research activities more favorably. For instance, for the November survey, respondents were more likely to perceive impact on data quality as favorable, compared with a perceived detrimental effect reported in the May survey. Reported impact on patient experience also was significantly more favorable on the second survey administration. However, reported effect of COVID-19 adjustments on patient safety and the respondents' own experience—although still considered beneficial—was less favorable when assessed the second time. One possible explanation is that—months into a pandemic in which patients, coworkers, and respondents themselves may have developed COVID-19—these adjustments may seem inadequate in the face of a highly infectious and potentially lethal disease. Alternatively, this trend might indicate that, over time, respondents felt that remote, virtual assessments do not provide as effective monitoring of study patients as do in-person visits. Finally, these responses may reflect pandemic fatigue.¹⁷ Although COVID-19 case rates, hospitalizations, and deaths were considerably higher in North Texas in November 2020 than at the time of the initial survey in May, by this time, health care professionals and the general public had grown more accustomed to the pandemic. For both behavioral and practical reasons, it has been reported that, as the perceived health threat of COVID-19 decreases, adherence to measures such as social distancing and self-isolation become more difficult over time.¹⁸ At the same time, the persistence and devastation of COVID-19 has resulted in heightened rates of professional burnout and depression among health care workers,^19,20 which may underlie the less favorable impression clinical research professionals had of their own experiences in the follow-up survey.

Currently, there are no established plans to continue COVID-19–related clinical trial adjustments after the pandemic ends. Doing so will require support not only from regulatory authorities, but also from clinical trial sponsors and payors. For instance, for years the FDA has encouraged centralized study monitoring (ie, remote evaluations) to simplify and reduce the cost of clinical trial conduct.²¹ Despite these recommendations, most trial sponsors and contract research organizations have failed to adopt such practices to a meaningful extent, a particularly notable observation, given the relatively widespread support for remote study monitoring, even among nonexperienced individuals, in this study. Similarly, even if telehealth for remote consent and study visits is permitted, this practice will not be sustainable if insurers stop reimbursing such encounters after COVID-19. Our findings suggest that clinical research professionals will continue to support extending certain COVID-19–related clinical research adjustments in the future, with greatest enthusiasm for remote study monitoring, telehealth visits, remote informed consent, and oral therapy shipment to patients' homes, but fewer than 20% of respondents recommended continuing off-site treatment. As with the initial May 2020 survey, respondent experience with a particular clinical research adjustment was consistently associated with recommendation to continue the adjustment in the future, an observation suggesting exposure heightens comfort and enthusiasm.

Our study has a number of limitations. The single-center setting reduces generalizability to other health care institutions. While the breadth of clinical research professionals represented among respondents allowed assessment of diverse trial considerations, it also resulted in unanswered questions, or unsure or no opinion answers. This was a particular concern for questions about extending COVID-19–related adjustments in the future, for which we were not able to distinguish between an unanswered question or an active recommendation not to continue a specific practice after the pandemic. Nevertheless, we were able to identify responses in favor of extending a COVID-19–related adjustment. We also recognize that asking clinical research personnel how patients and clinicians or investigators perceive these changes does not adequately represent the opinions of these other groups, who should be surveyed directly in the future. Indeed, asking respondents how they think these other groups perceive COVID-19–related adjustments may have directed responses to those most closely approximating observed reactions. Because surveys were conducted entirely anonymously, we needed to rely on self-report to identify respondents who completed both surveys. We were not able to compare responses for specific individuals between the initial and follow-up surveys, which would have allowed us to examine time trends according to respondent characteristics.

More than 6 months into the global pandemic, clinical research professionals in a single NCI-designated comprehensive cancer center continue to report favorable impressions of COVID-19–related clinical trial adjustments. In particular, individuals who have personal experience with changes such as remote consent, telehealth visits, shipping oral therapy to patients' homes, and remote study monitoring support continuing these practices into the future. Given the limitations of this study, conducting similar surveys in a multicenter setting and directly studying the perceptions of patients, clinical investigators, other clinical personnel, and sponsors will be important to understanding the broader response to COVID-19–related clinical trial adjustments. Additionally, studies to identify the impact of these changes on patient safety, data quality, and experimental treatment efficacy will inform the feasibility of making these changes permanent features of cancer clinical trials going forward.

APPENDIX

TABLE A1.

Recommendation to Continue COVID-19–Related Clinical Trial Adjustments in the Future According to (a) Experience With Adjustment and (b) Years of Experience as a Clinical Research Professional

AUTHOR CONTRIBUTIONS

Conception and design: David E. Gerber, Valerie L. Clark, M. E. Blair Holbein, Celette Sugg Skinner, Simon J. Craddock Lee, Erin L. Williams

Financial support: David E. Gerber, Celette Sugg Skinner

Administrative support: David E. Gerber, Valerie L. Clark, Erin L. Williams

Provision of study materials or patients: David E. Gerber, Simon J. Craddock Lee

Collection and assembly of data: David E. Gerber, Valerie L. Clark, Yang Xie, Celette Sugg Skinner, Erin L. Williams

Data analysis and interpretation: David E. Gerber, Thomas Y. Sheffield, M. Shaalan Beg, Yang Xie, M. E. Blair Holbein, Simon J. Craddock Lee

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Longitudinal Experience With and Impressions of COVID-19–Related Clinical Research Changes

The following represents disclosure information provided by the authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.

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