The perspectives on the clinical trials in South Korea under the impact of the global COVID-19 pandemic: the difference between trial site and sponsors

doi:10.21203/rs.3.rs-1461127/v1

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The perspectives on the clinical trials in South Korea under the impact of the global COVID-19 pandemic: the difference between trial site and sponsors

https://doi.org/10.21203/rs.3.rs-1461127/v1

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Background

During the COVID-19 pandemic, novel clinical trial methods known as decentralized clinical trials (DCTs) were rapidly introduced. The differences in operation of clinical trials including DCT perspectives during the pandemic between site and sponsors were investigated.

Methods

The effect of the COVID-19 pandemic on clinical trials was investigated for a society of sponsors and a trial site in South Korea. The current difficulties and future perspectives on clinical trials were assessed and compared between the site and sponsors.

Results

Both the site and sponsors reported on their experiences with the challenges of conducting clinical trials in the pandemic era. While 64% of personnel from the site judged that the difficulties were solved by their own solution, 67.6% of personnel from sponsors considered cooperation with trial sites as a key solution to overcome the difficulties. While half of the personnel from the site were skeptical of the changes in trial operation methods, the sponsors expect the institutionalization of DCT elements.

Conclusions

With varying attitudes, sponsors and sites attempted to overcome the challenges of conducting clinical trials during the pandemic era. To conduct clinical trials, both sponsors and sites must work closely together to find solutions with efficient communication. For the successful implementation of new tools such as DCT, the government needs to solicit support from sponsors and sites and change regulations.

clinical trial

decentralized clinical trial

virtual trial

COVID-19

sponsor

site

In 2020, the COVID-19 outbreak has compelled the governments of many countries to institute a full or partial societal lockdown [1]. Korea also implemented various policies including social distancing and partial lockdown [2]. The spread of COVID-19 gave rise to a burden in the healthcare system. The changes in the quarantine guidelines and people’s fear of infection minimized face-to-face contact, which resulted in the reduction in the use of healthcare units [3].

The COVID-19 pandemic also had an impact on clinical trials around the world [4]. Clinical trial participants tended to avoid face-to-face contact. The sponsors’ monitors had difficulty visiting the sites where clinical trials are taking place. Inspecting the sites was also difficult in some ways. Changes in the clinical trial environment hastened the transition to new approaches to clinical trial operation [5]. Before this pandemic era, novel methods for clinical trials called decentralized clinical trials (DCTs), also termed “direct-to-participant trials” or “virtual trials,” were introduced [6]. DCTs are defined as studies “executed through telemedicine and mobile/local healthcare providers, using processes and technologies differing from the traditional clinical trial model [7]. Although the new approaches are interested in the era of COVID-19 pandemic, the new methods to the clinical trial in some countries seem to be difficult to apply due to regulatory hurdles. In addition, the viewpoints of the new methods may be different between sites and sponsors. Our study investigated the difference in the perspectives to the clinical trials under the impact of the global COVID-19 pandemic between site and sponsors.

The current study was conducted based on two surveys for Korea Society for Clinical Development (KSCD), a society of soponsor group, and a survey for a domestic trial site. The surveys were performed for their own purposes. The ethics approval of this study was waived by the Institutional Review Board of CHA Bundang Medical Center (2022-03-041). The original questionnares of the surveys and English-translated versions are provided in Supplementary Material.

Surveys of KSCD

In July 2020, KSCD surveyed the impact of the COVID-19 pandemic on clinical trials in South Korea. A total of 42 personnel from each member company voluntarily responded to the survey (Table 1). The questionnaire covers the difficulties caused by COVID-19, the solutions to the difficulties, and the prospects after the pandemic. Personnel from domestic and multinational pharmaceutical companies (N = 14 and 16, respectively) and domestic and multinational contract research organizations (CRO; N = 7 and 5, respectively) responded. Half of the respondents (N = 22) were operation heads, managers, or directors. In 2021, KSCD surveyed post-COVID-19 DCT elements. A total of 36 businesses responded (Table 1). The survey included questions about the current state of DCT elements and their prospects.

Table 1

The general characteristics
Sites (N = 33)
Position
Professor	14 (42.4%)
Associate professor	13 (39.4%)
Assistant professor	4 (12.1%)
Clinical research coordinator	2 (6.1%)
Number of ongoing trials
20 or more	2 (6.1%)
10–20	1 (3.0%)
5–10	12 (36.4%)
1–5	15 (45.5%)
0	3 (9.1%)
The phase of clinical trials (N = 30; except for those without ongoing trial)
Phase 1	13 (43.3%)
Phase 2	16 (53.3%)
Phase 3	21 (70.0%)
Phase 4	10 (33.3%)
PMS	11 (36.7%)
Sponsors (year 2020; N = 42)
Characteristic
Domestic pharmaceutical company	14 (33.3%)
Multinational pharmaceutical company	16 (38.1%)
Domestic CRO	7 (16.7%)
Multinational CRO	5 (11.9%)
Position
Project manager	8 (19.0%)
CRA/PM line manager	6 (14.3%)
Operation unit head/manager/director	22 (52.4%)
General manager	6 (14.3%)
Sponsors (year 2021; N = 36)
Characteristic
Domestic pharmaceutical company	7 (19.4%)
Multinational pharmaceutical company	17 (47.2%)
Domestic CRO	5 (13.9%)
Multinational CRO	7 (19.4%)
CRO, a contract research organization

Survey of CHA Bundang Medical Center

In August 2021, a survey on the impact of the COVID-19 pandemic on clinical trials was conducted at CHA Bundang Medical Center in South Korea. A total of 33 personnel participated in this survey (Table 1). This survey also consists of the questionnaires of difficulties due to COVID-19, the solution for the difficulties, and the perspectives after the pandemic. Most responders were professors as investigators.

Challenges in conducting clinical trials due to COVID-19

In the pandemic era, personnel from both the site and sponsors face several challenges when conducting clinical trials (Table 2). Half of both sides’ respondents (43.3% from the site and 61.9% from the sponsors) thought that the clinical trials had been postponed, canceled, or discontinued. The site’s most common response was that it was difficult to enroll subjects (70.0%). Similarly, the most common response from sponsors was a schedule delay due to enrollment difficulties (85.7%).

Table 2

Hurdles in conducting clinical trials due to COVID-19
Sites (N = 30)
Postponement/canceler/discontinuation of trials	13 (43.3%)
Difficulties to enroll subjects	21 (70.0%)
Withdrawal of consents	1 (3.3%)
Difficulties to obey the protocol	11 (36.7%)
Difficulties to meet sponsor staff	16 (53.3%)
Sponsors (N = 42)
Postponement/canceler/discontinuation of new trials	26 (61.9%)
Increment in budget for trials	11 (26.2%)
Difficulties to manage research manpower	19 (45.2%)
Difficulties in business management (e.g., rescission of contracts)	6 (14.3%)
Delay of schedule due to enrollment difficulty	36 (85.7%)
Difficulties to obey the protocol	23 (54.8%)
Low reliability on data quality	7 (16.7%)
Other responses	5 (11.9%)
None	2 (4.8%)

Overcoming difficulties in conducting clinical trials

Twenty-five from the site and 34 from sponsors responded with experiences of problem-solving (Table 3). Most of the personnel from the site (64%) judged that the difficulties were solved by their own solution. Although many personnel from sponsors (67.6%) considered cooperation of sites were helpful, the investigators who felt cooperation of sponsors were supportive were relatively infrequent (24%). Numbers of personnel from sponsors (61.8%) responded that companies provided revised guidelines to solve the difficulties in conducting clinical trials.

Table 3

Experiences of problem-solving
Sites (N = 25, allowing duplicate responses)		Sponsors (N = 34, allowing duplicate responses)
Mitigation of COVID-19 spread	7 (28.0%)	Mitigation of COVID-19 spread	20 (58.8%)
Cooperation of sponsors	6 (24.0%)	Cooperation of sites	23 (67.6%)
Support from site hospital	1 (4.0%)	Provision of guidelines by the company	21 (61.8%)
Investigator’s solution	16 (64.0%)	Others	3 (8.8%)
Solutions to overcome difficulties		Solutions to overcome difficulties
Phone contact instead of direct visit	10 (47.6%)	Allowance of phone visit	19 (45.2%)
Using e-consent	1 (4.8%)	Introduction of e-consent	3 (7.1%)
Remote data collection	2 (9.5%)	Telemetry/digital data collection	14 (33.3%)
Use of local clinic	1 (4.8%)	Direct-to-patient shipments of IP	15 (35.7%)
Shipment of IP by parcel service	1 (4.8%)	Central lab	5 (11.9%)
Visit by home health nurses	0 (0.0%)	Home health nurse system	2 (4.8%)
Remote site contact without a direct visit	12 (57.1%)	Remote site monitoring	26 (61.9%)
Unsolved	1 (4.8%)	Remote SDV/SDR	10 (23.8%)
Wait until solved	1 (4.8%)	None	6 (14.3%)
		Self-medication program	1 (2.4%)
IP, investigational product; SDV, source data verification; SDR, source data review

Sponsors tended to try to incorporate different types of DCT elements (Table 3). In contrast, site investigators were far from DCT elements when attempting to solve the problems. The investigators’ most common method of contact with the subjects (47.6%) was simply by phone.

The perspectives on the changes in the operation of clinical trials after the pandemic

The sponsors hoped that DCT elements are needed to be institutionalized soon. The sponsors look forward to regulation changes accepting DCT tools (Table 4). In contrast, half of the personnel at the site never expected the changes in the methods of the clinical trial (45.5%, Table 4). While the personnel at the site ranked direct contact with the aid of telemedicine tools including remote access, e-consents, and remote monitoring as new methods, methods to use home care nurses and another clinic instead of the real sites were not favored. Furthermore, most of the personnel at the site were not aware of terminologies indicating new trial methods such as DCT (Table 5).

Table 4

The site and sponsors’ perspectives on the changes in the operation of clinical trials after the pandemic
Survey at the site
Changes in the operation of clinical trials after pandemic (N = 32)
No changes, return to the past	15 (45.5%)
New methods including telemedicine and intact trial	17 (51.5%)
No idea	1 (3.0%)
Kinds of elements in the changes (N = 20, allowing duplicate responses)
e-Consent	11 (55.0%)
Remote practice	14 (70.0%)
Direct-to-patient shipments of IP	9 (45.0%)
Remote assessment	12 (60.0%)
Visit by home health nurses	2 (10.0%)
Use of local clinic	5 (25.0%)
Remote site monitoring	12 (60.0%)
Survey for sponsors
Kinds of elements in the changes (N = 36, allowing duplicate responses)
Digital data collection tools	34 (94.4%)
Remote monitoring and sponsor visits to study sites	32 (88.9%)
Direct-to-patient shipping	30 (83.3%)
Electronic informed consent	29 (80.6%)
Electronic health records and electronic data capture	24 (66.7%)
Home health visits	23 (63.9%)
Telemedicine	20 (55.6%)
Local lab use	19 (52.8%)
IP, investigational product

Table 5

The investigators’ awareness of new clinical trial methods
N = 25, allowing duplicate responses
Virtual clinical trial	7 (21.2%)
Decentralized clinical trial	5 (15.2%)
Remote clinical trial	9 (27.3%)
Direct-to-patient trial	1 (3.0%)
Unawareness	13 (39.4%)
No response	1 (3.0%)

In the pandemic era of COVID-19, both the site and sponsors have faced many challenges in conducting clinical trials. The most important tasks in resolving the issues are preventing the pandemic spread and communicating with sites and sponsors. While the site investigators favored indirect contact using telephone and email, the sponsors desired to introduce various tools of DCTs.

The investigators at the site strongly believed that the difficulties could be overcome by themselves despite the pandemic environment. In addition, half of the personnel at the site not only were unfamiliar with the terminologies of novel methods on clinical trials but also had skeptical insights into them. It advocated for a cautious approach to the changes in clinical trial methods. With sposnors’ support, the site investigators must take action against the changes [8]. Our study showed a gap between site investigators and sponsors. Sponsors are more prepared to use DCT elements than site investigators. As site investigators does not recognize the benefits of DCT in terms of patients perspectives, both parties must communicate more efficiently with one another [9]. As the sponsors are required to train clinical research associates (CRAs), CRAs need to play more roles to communicate with site personnel [10]. Each site needs to prepare a new standard operating procedure according to the government’s guidelines and to train the affiliated personnel.

As known well, the COVID-19 pandemic disrupted many clinical trials that were potentially bringing new therapeutics to market [11]. As a result of this crisis, the US Food and Drug Administration, alongside its international counterparts, has developed guidance to protect both research participants and trials by advocating for remote data collection supplemented by telemedicine [12]. The regulatory authorities must set the direction for resolving the issues by developing guidelines. According to global data 2021, digitalization of preclinical and clinical trials was viewed positively by 39% of healthcare and pharmaceutical professionals in North America, 39% in Europe, and 28% in the Asia-Pacific region [13]. In our study, clinical trial sponsors believed that DCT items, such as digitalization, were required for successful clinical trials even after the pandemic era. However, some DCT items cannot be used in some countries including South Korea due to regulatory hurdles [14, 15]. Hence, regulatory authorities need to find hurdles with sponsors and sites and to solve those hurdles. In addition, trial sites also need to support remote monitoring performed by sponsors.

This study has several limitations. First, contrary to the sponsors, only one trial site was considered for the survey. Although overestimation of our result is cautious, it is advisable to see a viewpoint of the personnel working at the site. Second, one of the surveys for the sponsors was conducted the previous year; due to the interval between the surveys, the pandemic status, policy response, and social attitude may be different from the two points. However, even in this advanced year, it is interesting to note that many site investigators remain unaware of new approaches to conducting clinical trials. Third, the subjects who participated in clinical trials were not surveyed on. Changes in trial methods have a direct impact on the subjects. The changes must be geared toward the subjects’ benefit and convenience.

Despite many common hurdles in conducting clinical trials during the pandemic era, sponsors and sites were trying to overcome the hurdles with different attitudes. The COVID-19 pandemic has accelerated the implementation of decentralized clinical trial solutions, and DCT will be used in clinical trials more and more in the future, with benefits for sponsors and sites. Furthermore, decentralized solutions improve the patient experience. Both sponsors and sites need to have close communication and find solutions when they face difficulties like COVID-19 in conducting clinical trials. In addition, sponsors and sites need to share feasible solutions and coordinate to train the personnel involved in the clinical trial. The government needs to gather opinions from sponsors and sites and change regulations for the successful implementation of new tools like DCT.

CRA, clinical research associate

CRO, contract research organization

DCT, decentralized clinical trial

KSCD, Korea Society for Clinical Development

Ethics approval and consent to participate

This study is based on the surveys performed for their own purposes. The participants answered to the questionnaires of the surveys anonymously. In this reason, the need for consent to participate was waived by the Institutional Review Board of CHA Bundang Medical Center (2022-03-041).

Consent for publication

Both KSCD and CHA Bundang Medical Center agreed on the publication of the article.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

None

Authors' contributions

Substantial contributions to the conception or design of the work: YS Lee

interpretation of data for the work: YS Kim and YS Lee

Drafting the work or revising it critically for important intellectual content: YS Kim and YS Lee

Final approval of the version to be published: YS Lee

Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: YS Lee

Acknowledgements

The authors thank to Korea Society for Clinical Development on conducting surveys and sharing the results.

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Reviews received at journal
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Reviewers invited by journal
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Editor assigned by journal
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First submitted to journal
03 Apr, 2022

You are reading this latest preprint version

The perspectives on the clinical trials in South Korea under the impact of the global COVID-19 pandemic: the difference between trial site and sponsors

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Abstract

Background

Methods

Results

Conclusions

Background

Methods

Results

Discussion

Conclusions

List Of Abbreviations

Declarations

References

Supplementary Files

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