Research ethics and integrity challenges in accelerated clinical trials, an interview study

Abstract

Background

Accelerated clinical trials for drugs and vaccines during global health crises allow for rapid access but pose research ethics and integrity challenges. Understanding these challenges is crucial for preserving research participants’ safety and supporting research fairness and trustworthiness. This study aims to explore the research ethics and research integrity challenges associated with the acceleration of clinical trials.

Methods

This qualitative interview study used semi-structured online interviews with key stakeholders in the regulation, design, implementation, and publication of clinical trials as professionals (i.e. trial experts from academia, pharmaceutical companies, non-governmental organizations and national and international regulatory authorities and publishers) recruited using purposive sampling. Interviews were conducted online from April to July of 2023. Transcripts were thematically analysed using deductive and inductive coding through MAXQDA software.

Results

The main challenges identified were: amplified familiar challenges related to participant recruitment and informed consent; lack of guidance for, and pressure on, ethics and scientific review processes; missing strategies and ambiguous responsibilities in public communication; and poor collaboration, coordination and competition for research resources and supportive structures among research groups Recommendations included: greater engagement with patients throughout the accelerated clinical trial process from design to implementation; providing Research Ethics Committees with specific training on accelerated trials; promoting transparent public communication; fostering international collaboration; and shifting from an industry-centred to a people-centred acceleration.

Conclusion

These findings highlight the need for systemic changes in the conduct of accelerated clinical trials, including the openness of clinical research and international coordination to address ethical and integrity issues, ensuring scientific rigor and public trust and promoting justice.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12910-025-01328-9.

Background

The urgency of global health crises, such as infectious diseases outbreaks, have stimulated the rapid development of drugs and vaccines through accelerated clinical trials [1–3]. Accelerated clinical trials have also been promoted to allow for increased time of market protection and improved productivity in the pharmaceutical industry [4, 5]. Some examples of accelerated trials include those conducted for the Ebola virus disease (EVD) vaccine, after the 2013–2016 outbreaks in West Africa [1, 2], and the trials for two treatments for drug-resistant tuberculosis (XDR-TB), after it was considered a serious public health threat in 2006 [3, 6]. Accelerated clinical trials are clinical trials with a shorter clinical development time than average, regardless of the underlying cause of that acceleration. This type of trials have shortened their time through expedited regulatory processes, faster recruitment, adaptive trial designs, or parallel manufacturing and trial activities. The COVID-19 pandemic catalysed an unprecedented rise in the number of accelerated clinical trials aimed at developing effective treatments and vaccines [7], many of which employed innovative methodologies (such as multi-arm, multi-stage, and adaptive trial platforms) or the large-scale manufacturing of multiple vaccine candidates before approval [8]. While these accelerated processes can provide benefits for different stakeholders, they can also present significant ethical and integrity challenges, undermine public trust and even lead to inequities in healthcare access [8].

Understanding research ethics and integrity challenges in accelerated clinical trials is crucial to protect research participants and to ensure the quality and trustworthiness of scientific advancements [9, 10]. Research integrity refers to the combination of professional standards ensuring the validity and trustworthiness of research [11, 12], while research ethics addresses the moral issues associated with, or that arise in the course of, pursuing research [12] – these typically concern the protection and autonomy of research participants, as well as issues of justice in relation to who is selected for research and who receives the benefits of research [13, 14]. Some aspects of RI and RE, such as trust and justice, might be particularly affected by accelerated clinical trials. In RI, trustworthiness plays a foundational role in ensuring participation and public support for clinical research, especially under conditions of urgency and uncertainty [10]. In RE, justice has been a key consideration since the Belmont Report [13], and has been further elaborated in the more recent updates to the Declaration of Helsinki. Justice is particularly important in accelerated trials where some social and geographical population groups may otherwise be overlooked [8].

A number of ethics and integrity issues associated with clinical research and trials during the COVID-19 pandemic have already been identified in opinion pieces, first-hand accounts, and articles [15–22]. These articles report on research ethics and integrity challenges such as: processes of informed consent and participant monitoring becoming challenging due to public health measures during the pandemics [22, 23]; unfair research resources and benefits allocation [18, 19]; fast-track review by Research Ethics Committees (RECs) in urgency situations [16]; duplication of studies and competition for participants leading to unrepresentative and small samples [15]; lack of transparency and publication bias in COVID-19-related studies from pharmaceutical companies [7] or systematic exclusion of vulnerable and/or marginalized populations in COVID-19-related clinical trials [24–26].

Despite some of these challenges being identified from firsthand experience, there remains a notable lack of primary research related to the ethics and integrity challenges associated with accelerated clinical trials in practice in the European context that focuses on the views of key stakeholders involved the regulation, design, implementation, and publication of clinical trials as professionals. Previous empirical research has only focused on the research integrity challenges experienced by health sciences researchers – not only on clinical trials – during COVID-19 at one institution [27] and on the solutions to challenges related to clinical research in pandemics and epidemics other than COVID-19 [23]. This study aims to address this gap by exploring the research ethics and research integrity challenges associated with the acceleration of clinical trials according to clinical trial experts.

Methods

Study design

This is a qualitative interview study. The data collected are used for two different studies: the present study and another in preparation study by van Eck et al., which aims to determine the drivers for accelerating trials in Europe. Semi-structured interviews were performed by authors CPP and LE, located in Amsterdam, The Netherlands and conducted online from April to July of 2023, with key stakeholders involved in the regulation, design, implementation, and publication of clinical trials as professionals.

Participant recruitment

A purposive sample of key stakeholders key stakeholders involved in the regulation, design, implementation, and publication of clinical trials as professionals in Europe were recruited via the varied and extensive professional networks of all of the authors, including European research projects and past and present collaborations (among others), and additionally asking participants to identify and invite further participants (snowball sampling).

For this study, key stakeholders were defined as experts involved in the regulation, design, implementation, and publication of clinical trials as professionals. We recruited a diverse sample of experts working in different organisations relevant to these areas of clinical trials. This included professionals affiliated with scientific journals, clinical researchers, policy advisors, clinical trial development advisors, bioethics experts, pharmaceutical companies professionals and, non-governmental organisations (NGOs), European Medicines Agency (EMA) professionals, National Competent Authorities from different European countries, World Health Organization (WHO), and European Commission representatives. While we successfully recruited participants from many of these categories, we were unable to include representatives from the WHO and European Commission, despite efforts to do so. The final sample composition and detailed participant characteristics is included in the Results section.

All participants received a standard invitation letter introducing the study. After accepting the invitation, participants signed an informed consent (Supplementary file) form and filled in a short questionnaire (Supplementary file) designed to collect their demographic information and their specific expertise in the field of clinical trials. Furthermore, to ensure a shared understanding of the term ‘accelerated clinical trials’, a concise and established definition was shared with participants both prior to and during the interviews:

Accelerated clinical trials are clinical trials with a shorter clinical development time than average, regardless of the underlying cause of that acceleration. This type of trials have shortened their time through expedited regulatory processes, faster recruitment, adaptive trial designs, or parallel manufacturing and trial activities.

Data collection

Semi-structured video-call interviews were performed online by LE alone (14 interviews) or together with CPP (11 interviews). Interviews had a planned duration of 30 min and were recorded after receiving verbal and written consent by participants. Semi-structured interviews were conducted using an interview guide with questions regarding the drivers for acceleration of clinical trials and associated ethics and integrity challenges (Supplementary file). The interview guide was developed in the context of two related studies (one focusing on the drivers of accelerated clinical trials in Europe, and the present study on ethics and integrity challenges). Thus, it included questions covering both areas, some aiming to identify the drivers for acceleration and others aiming to identify the research ethics and integrity challenges of accelerated clinical trials. Challenges related to RE and RI were however described in response to all questions, therefore all responses were analysed for this paper, not just those in response to the specific RE/RI challenges questions. Regarding research ethics and integrity challenges related to accelerated clinical trials, experts were asked for social and ethical challenges, the trustworthiness of results, and public trust. Experts were also free to bring up any issue they considered important to the integrity and ethics of accelerated trials. The interview guide was first piloted with a post-graduate student and with a global health researcher using the ‘thinking-aloud’ method [28] and subsequently refined.

Data analysis

Interviews were transcribed using the GDPR-compliant AI tool Amberscript (www.amberscript.com) and checked for accuracy by LE and/or CPP. Amberscript applies encryption and secure data handling protocols, and all files were deleted from the platform after transcription in accordance with institutional and platform data protection guidelines. For the present study, transcripts were analysed in MaxQDA software using a thematic approach to identify cross-cutting analytic themes in the data using a combined deductive and inductive coding approach [29]. A preliminary deductive code-tree was developed reflecting research ethics topics covered by the Declaration of Helsinki [30] and research integrity topics covered by the Singapore Statement for Research Integrity [11]. This code tree was used to analyse 10 interviews by CPP and GI. New (sub)codes which focused more on the experts’ experience of the ethics and integrity challenges were inductively added. This new coding scheme was used to code the whole data set, with any new additional inductive codes or disagreements in coding being iteratively discussed by the first and second coders (CPP and GI). After the analysis of the 25 interviews, deductive codes which were not reflected in the data were deleted and the final coding scheme was discussed by CPP, GI and NE. CPP developed the analytic themes by grouping related codes to represent the research ethics and integrity challenges experienced by experts, minimizing overlap. The themes were reviewed and refined in team meetings.

Ethics approval

We performed an online ethics review self-check via the website of the Ethics committee of the Faculty of Science (BETHCIE), Vrije Universiteit Amsterdam (Supplementary file). In this self-check a series of questions is used to determine whether your research complies to the Code of Ethics for Research involving Human Participants Faculty of Science. Our research did conform to this code, and further review by the BETHCIE was not required. However, we indicated that we would collect personal data, and/or that the identities of the participants are known to the researchers, and therefore we needed to pay particular attention to the research data management plan (Supplementary file). Additionally, all participants filled out an informed consent form.

Positionality and reflexivity

This study was conducted by a European research team, based in the Netherlands, and involved in several EU-funded research projects. The first author has a background in biomedicine, bioethics and public health and led this study as part of her doctoral research focused on Epistemic Injustice and research ethics and integrity. The first author and her supervisors are affiliated with the department of Ethics, Law and Humanities at Amsterdam University Medical Centre (UMC). Other members of the research team are affiliated with Centre for Tropical Medicine and Travel Medicine at the same institution and contribute to international initiatives focused on improving practices in clinical research. Our research foci and involvement in European projects informed both the framing of our research questions, our access to participants, and our interpretation of the data. Our proximity and expertise in the topic of RE and RI is reflected in the choice of focus of this article.

Results

Participants demographics

A total of 25 out of 192 invited people agreed to participate in this study. The sample included five experts working at large pharmaceutical companies, three experts working at the EMA, three working at different national competent authorities (NCAs), and 13 experts that were experienced researchers in global health, bioethics experts, policy advisors, professionals working at different NGOs, as well as editors at academic publishing groups (Table 1). Most participants [20] worked in clinical trials for more than ten years and 16 were educated to PhD level (Table 2). Participants were working either in Europe, the United States, or Canada at the time of being interviewed and all of them had professional experience linked to European organisations or research centres/projects.

Table 1.

Participants categorized per stakeholder group

Stakeholder group	No. of participants	KOL specifications**	No. of participants
Key opinion leaders (KOL)*	13	Senior editor scientific journal	1
		Senior researcher in health sciences	1
		Policy advisor	8
		Clinical trial development advisor	1
		Bioethics expert	4
		NGO	2
Pharmaceutical companies	6
European Medicines Agency	3
National Competent Authorities	3

*The breakdown of the key opinion leaders is specified in column 3 and 4

**Many key opinion leaders fulfilled multiple roles

Table 2.

Participants demographics

Demographics	Category	No. of participants
Gender	Male	16
	Female	9
Age category* (in years)	31–45	9
	46–60	8
	60+	6
Highest level of education*	Master’s degree	8
	PhD	16
Relevant work experience (in years)*	1–3	1
	5–10	3
	10+	20
Country of current employment *	The Netherlands	8
	United Kingdom	4
	Switzerland	3
	Belgium	2
	Bulgaria	1
	Czechia	1
	France	1
	Greece	1
	United States	2
	Canada	1

*Two participants did not or only partly completed their questionnaire

Themes

Four themes were identified relating to ethics and integrity challenges in accelerated clinical trials:

1. Familiar ethics and integrity challenges amplified.

2. Pressure and gaps in scientific and ethics review.

3. Missing strategies in public communication.

4. Collaboration, coordination and competition.

These themes are described below. Furthermore, each theme includes recommendations for potential solutions which were offered by the experts.

Experts had diverse perspectives on the occurrence of ethics and integrity challenges associated with accelerated clinical trials. While bioethicists and policy advisors rapidly identified challenges, other groups, including researchers, professionals working in pharmaceutical companies and NCAs representatives, found it difficult to explicitly identify ethics and integrity challenges related to accelerated trials. All the experts, however, described ethics and integrity challenges familiar to clinical trials but exacerbated by accelerated timelines. These include recruitment and inclusion of participants and informed consent.

Recruitment and inclusion of participants

Some experts highlighted that problems related to the representativeness of samples and the exclusion of groups considered vulnerable, such as children and pregnant women, are exacerbated in accelerated clinical trials because including vulnerable populations requires special ethical attention which might increase the duration of review processes. As a result, according to Expert 5, a researcher and policy advisor, these populations are even less frequently included in accelerated clinical trials.

Informed consent

Experts suggested that accelerated clinical trials during public health emergencies could potentially increase the pressure on researchers to persuade patients to participate in research:

We still have to [ensure] informed consent. And the persuasiveness of the investigator is something we can’t know. We don’t know from our perspective. We know, of course, that some investigators are more successful to find patients […]. Yes, that depends a lot on how patients are informed on the trial and how they are informed. But that’s up to the investigator. So, we are very far from knowing what is really happening. We ask that in discussions. How do you inform your patients? What do you do? And yes, there’s a lot of difference. (Expert 20, professional working at a large pharmaceutical company)

Some experts discussed the extra difficulties of the informed consent process in COVID-19 decentralised trials, in which such processes were conducted digitally. While online consent procedures are more efficient, one ethicist and policy advisor raised the concern that the lack of human interaction between the research participant and the medical team poses a challenge to the informed consent process since it might lead to lower understanding of the research study.

Recommendation: patient-centred trials

For some experts, engaging patients and research participants in all trial phases, including participation in the set-up of the study design, is essential to address the ethics and integrity challenges associated to accelerated clinical trials. This would allow for more efficient and rapid trials, as well as for increased preparedness and transparency. According to some experts working in clinical trial consultant and regulatory agencies, there is a need for a shift in the design of trials and a deviation from regular practice: efficient methods and adequacy in accelerated trial design encompasses listening to patients’ voices in all stages of the clinical research process including design, execution and outcome:

We need to collaborate much earlier with patient organizations to really make sure that [they] define the right clinical trial objectives, clinical endpoints, target population, because quite often industry is still sometimes misusing the word that any type of product is addressing an unmet need. But this is not always the real case. And if they come up with a clinical trial design or specific endpoints, they are not absolutely always the most relevant ones for the final target population for the patient. […] (Expert 19, professional working at a National Competent Authority).

Theme 2: pressure and gaps in review

Several experts raised concerns about the ethics and scientific review process of accelerated clinical trials which started during the COVID-19 pandemic. During the pandemic, Research Ethics Committees (RECs) faced incredible pressure and often had to improvise their review processes due to reduced timeframes and a lack of guidance and knowledge regarding fast track reviews, novel research designs, and new methodological procedures. For example, a bioethicist and policy advisor working in Europe described a case in which protocols were reviewed solely by the REC’s chair at a university, rather than by two reviewers and a chair as typically required. This deviation was due to the shortage of time, guidance, and the increased volume of protocol submissions:

I think it’s really important that ethics committees have the right guidance around fast track procedures because we do need to be able to respond quickly in a pandemic […]. [When the pandemic broke out] no one really knew what to do in terms of this. So it was just ‘come up with some sort of way for COVID 19 research to be prioritized and have a quicker review’. So instead of it going to the normal two reviewers and a chair, it’d go to like, I think, just a chair or a chair and one reviewer in some cases. But if that’s the case, then we need to make sure that all the things are still being considered. It doesn’t mean that you should just not consider all the ethical considerations because it’s fast track.” (Expert 9, Bioethicist and policy advisor).

Experts also expressed concerns about the lack of a separate scientific review in addition to the ethics review in accelerated trials. At the European level, as stated by a bioethicist and policy advisor, it is unclear who is responsible for reviewing the techno-scientific aspects of trial protocols. On many occasions, the absence of an external body to review methodological issues results in these aspects being neglected, as RECs often lack the skills or time to conduct them thoroughly. According to some experts, this was particularly true during the COVID-19 pandemic due to the increased number of protocols they had to review and the extremely short time to review them.

Recommendation: improving skills and defining responsibilities

Some experts identified potential ways to improve knowledge and skills of RECs. Additional training for REC members and development of crises procedures was suggested by two experts, one working at the EMA and the other at a National Competent Authority. These experts suggested establishing a European REC advisor which could serve as a point of reference in times of crises, and proposed greater collaboration between RECs with different expertise at a European level. Regarding scientific review, one expert, a bioethicist and policy advisor, suggested to establish regulations that make sponsors responsible for assessing studies methodology and feasibility across Europe, a measure that could benefit not only accelerated clinical trials, but also traditional clinical trials in general.

Theme 3: missing strategies in public communication

When asked about public trust in accelerated clinical trials, nearly all experts agreed that communication is a key research integrity challenge. Experts emphasized that communication is essential to ensure scientific advancements have societal impact. Without clear communication, the public may not understand why clinical products can be developed faster, endangering trust. Identified challenges include public understanding of accelerated procedures and ambiguity of responsibilities in science communication.

Public understanding of accelerated procedures

Experts said that accelerated clinical trajectories have an impact on how the public perceives the outcomes of clinical research. The experts’ common view was that acceleration is appropriate in emergency situations, however they were sympathetic with the public’s concerns given the lack of properly communicated information. Especially during the COVID-19 pandemic, some experts said, it was comprehensible that people questioned why the process of obtaining a vaccine was much shorter than for other diseases. A bioethicist and policy advisor stated that COVID-19 related-accelerated trials were completely safe, and that if the general public perceived accelerated trials as more risk-prone, this was due to a failure in communication:

I think a lot of it has to do with communication and understanding of what’s different and why it’s [the clinical trial] fast, because I think a lot of people have a misperception that corners are being cut and that there’s not sufficient evidence or that if they are the first ones to get it [vaccine] marked authorization are going to be still sort of guinea pigs […] So again, to me that was a communication failure, not an ethics failure. (Expert 8, Bioethicist and policy advisor)

The ambiguous responsibility of science communication

Experts agreed on the idea that preserving public trust in science is the responsibility of all research stakeholders, including industry, media, and government, yet roles remain unclear in accelerated trials. Most experts said that lack of defined responsibilities for communicating results contribute to a lack of effective communication strategies. One global health researcher highlighted how pharmaceutical companies developing COVID-19 vaccines failed to explain clearly how the process of drug or vaccine development works, which led to public hesitancy to use them. Experts added that the lack of communication strategies in publishers was evident when studies turn out to be questionable, like in the case of the discredited hydroxychloroquine studies during the COVID-19 pandemic. Some experts also pointed out that political leaders’ can influence trust in science. If politicians do not adequately discredit fake news, or if there is a widespread sense of distrust in political leaders, the quality of public scientific discourse is damaged:

Much of the mistrust in science has nothing to do with the science itself. It has to do with the social and political context in which the science is done and presented. And if there is mistrust in the government. Then there’s only so much you can do as a scientist. (Expert 10, experienced global health researcher and policy advisor)

Recommendation: honesty, transparency, preparation and public involvement

The recommendations proposed by experts to enhance public trust varied widely, ranging from adhering to moral values such as honesty and transparency to more practice-driven solutions.

Honesty and transparency

Some experts described honesty and transparency as crucial values in the trust-building process. Adhering to these values also means fostering public understanding of the scientific process and the evolving state of scientific knowledge:

I think honesty in the communication with the general public is essential to make them understand how vaccines and drugs are developed, to make them understand what kind of controls and checks and attention to ethical elements are put into clinical research […]. And then we need also to be honest: we have seen it at the beginning of the COVID pandemic, that when data from clinical trials are published that’s not the end of the road. Additional information will be added with the deployment of drugs and vaccines. So, we will still learn after that. And it needs to be clear that knowledge will progress. (Expert 2, senior editor at an academic publishing group)

Public and patient involvement (PPI)

Experts advocated for clinical research to be more open, inclusive and understandable to improve the trust-relationship between the general public and the scientific community. Involving the public was also a recurrent recommendation. Practical recommendations to achieve this included: allocating more funding to awareness campaigns and patient advocacy groups, investing in communication experts for all research centres, and involving patient representatives in decision-making processes.

Theme 4: collaboration, coordination and competition

Experts discussed the challenges associated with poor international coordination and collaboration, and competition, and how these can directly lead to injustices in research. In crises situations, given the lack of international coordination, high economic incentives paired with urgency and competitive pressures can lead to fragmentation and duplication of trials and to the exacerbation of existing inequalities.

Fragmentation and duplication of research efforts in COVID-19

Duplication of clinical trials was discussed by some experts with ethics backgrounds or professionals in national and international regulatory agencies. In the COVID-19 pandemic, the urgency to find effective treatments, combined with competition, and lack of coordination led to trial duplication. This was defined as a ‘scandal’ by a bioethicist and policy advisor, who focused on a personal experience:

So I […] spent all my time in this hospital, and one of the first things I saw was that there were two competing trials, ones set up by one hospital, and the other one, I think by the Ministry of Health. They were competing for the same patients. This to me was crazy because we were losing time, duplicating efforts. There were nuances from one study to the next, and the whole COVID story is a scandal. There were hundreds of trials which were totally useless, done by people who were chasing the funds and wanted to have their name on papers. And this was an incredible waste of everyone’s resources, time and money and in fact exposed the whole society to delayed results. Look at the whole chloroquine scandal. (Expert 15, Bioethicist and policy advisor)

When efforts are fragmented, there is competition for resources and supportive structures (including patients, personnel, spaces, bureaucratic systems, and technical materials) which can lead to wasted efforts and underpowered trials. During the COVID-19 pandemic, experts said, this did not only mean that resources were wasted on poor quality studies representing a research integrity challenge, but also that they led to inconclusive results and even affected patients’ safety, being also a research ethics challenge. A bioethicist and policy advisor expanded on the example of accelerated trials for ivermectin as a COVID-19 treatment, which put research participants’ health at risk:

[Y]ou had hundreds and hundreds of poor quality, high biased trials being initiated, the vast majority of which were never completed. And those that were completed were at such high risk of bias that they’re not the kind of trials that we should be following. And that science was not only wasted, it actually harmed patients. So, if you look at the ivermectin systematic review, the first systematic review that was published, they included all of the trials. And including ones that had a very high risk of bias or even kind of outright fraud. And they initially concluded that ivermectin was something that was effective for the treatment of COVID-19, which led to patients being given this toxic and ineffective drug. (Expert 11, Bioethicist and policy advisor)

Economic incentives

Experts pointed out that economic and commercial interests, paired with high competition and urgency play a very important role in the development of accelerated clinical trials, with associated research ethics, integrity and justice issues. In particular, they discussed how economic interests can act as perverse incentives and lead to research ethics issues such as health risks for patients and participants safety, research integrity issues such as publication pressure and poor practices of open science, and justice issues such as unequal prioritisation in acceleration.

Safety issues

Firstly, acceleration for economic reasons might become a research ethics challenge, since it can overlook secondary effects of the developed product because it is tested in fewer patients due to time constraints. Furthermore, two researchers in global health pointed out how in order to rapidly expand the market, the use of vaccines can be incentivised in children or other groups, even when lacking a complete safety profile for such population groups.

Publication and open science issues

Secondly, experts discussed how competition and a widespread sense of urgency in times of COVID-19 pressured research groups in the Global North to push articles out quickly, resulting, in some cases, in low-quality articles. Moreover, several experts stated that economic incentives played a role in the way knowledge was exchanged during the COVID-19 vaccine development. Although open science and open data can accelerate discovery and progress during a crisis, the private sector did not always share knowledge with other parties. According to a global health researcher, this led to delays, wasted money and time and contributed to increase inequalities between countries in terms of access to the COVID-19 vaccines.

Prioritisation issues

Finally, experts highlighted how economic interests can lead to unequal prioritisation of research since these often dictate the agenda setting of acceleration. This can exacerbate global inequalities in health, research contribution and access to scientific advancements. Researchers working in the field of global health and policy advisors, pointed out that acceleration normally only occurs for diseases affecting high income countries, even though a health need exists for other diseases affecting less economically privileged regions, According to a global health researcher and policy advisor this was easy observable during the COVID-9 pandemic, which functioned as a ‘double-edged sword’, allowing for rapid access to COVID-19 vaccines, but delaying progress on the development of treatments for other diseases. The effects on other diseases and its treatments such as Mpox vaccines or XDR-TB drugs were described:

In theory, all patients are equal. But when you look at tuberculosis and COVID-19, you have 1.5 million killed by COVID-19 and 1.5 or 1.6 million killed by tuberculosis. And if you look at the resources directed to this disease and to the other disease, the only difference will be the areas that these patients are [infected with]. (Expert 24, professional working at an NGO)

Overall, experts agreed that economic incentives and commercial pressure driving acceleration can reinforce the lack of access to pharmaceutical products and biomedical knowledge because they are not an attractive economic contributor or lucrative market in the biomedical research race.

Recommendation: equitable knowledge sharing and governance in science

In general, experts advocated for international governance of clinical trials that includes the voices and needs of low-and-middle-income countries (LMIC), emphasizing knowledge sharing between nations and private-public collaboration, especially during crises. A global health researcher described how two major pharmaceutical companies developing COVID-19 vaccines denied knowledge access to South Africa’s mRNA vaccine technology hub during COVID-19, hindering LMIC vaccine production. Regulatory agency experts also stressed the need for better global coordination during international health emergencies. An EMA expert noted the importance of involving other regions in clinical trials, starting with strong European infrastructure but expanding to global collaboration for faster, more effective trials.

Discussion

Our study revealed that there are relevant and unique research ethics and integrity challenges associated with accelerated clinical trials. Whereas previous articles identified challenges such as adapting consent processes [22, 23, 31], allocating fairly resources in research during emergencies [18, 19] or shortening REC review processes [16], this study brings forward the views of a broad variety of key stakeholders, mapping key ethics and integrity issues to the literature. Newly identified challenges include: pressure to obtain informed consent or exclusion of certain population groups; pressure and lack of knowledge and guidance for fast-track ethics review; poor science communication and a lack of defined communication strategies affecting public trust; and economic incentives, high pressure and lack of coordination and collaboration exacerbating global inequalities. Experts also provided potential ways to address the challenges, including public engagement and international collaboration strategies.

Ethical challenges in accelerated clinical trials are sometimes not immediately recognized by clinical trial stakeholders, including some of our experts, but exist beneath the surface and, on many occasions, go beyond the foci of research ethics reviews. The study by Godskesen et al. [32] aligns with these findings and confirms that clinical trials professionals often rely solely on RECs to identify and deal with ethics issues, revealing an epistemic ethics gap in researchers’ and other professionals’ knowledge, which can result in a lack of attention to ethics issues.

Despite many experts considering REC review to be sufficient for accelerated trials to be conducted at the highest ethical standards, shortcomings were described. Our ethics experts and policy advisors reported that RECs faced heavy workload and insufficient guidance during fast-track reviews of COVID-19-related trials and that scientific review was often lacking. Previous literature has attributed this problem to the absence of national regulations for RECs, lack of collaboration between researchers, and poorly designed protocols [15, 16]. However, less attention has been paid to the lack of specific training and guidance and unclear distribution of responsibilities in the scientific review of accelerated clinical trials. In Europe, according to the Clinical Trials Regulation, clinical trials assessment is divided in two parts: Part I covers techno-scientific matters, including pharmaceutical quality or trial methodology, while Part II includes locally relevant issues such as informed consent [33, 34]. Although the responsibility for assessing each part can be decided by each member state, ethical issues can arise in both parts, meaning that in many countries RECs end up assessing Part I and Part II falls [35]. While RECs’ involvement can enhance ethical surveillance, this increases the pressure felt by REC members, who already lacked guidance and knowledge regarding accelerated trials during the COVID-19 pandemic.

Our study suggests that a lack of global coordination, competition and economic interests can also have consequences for the relevance and robustness of accelerated clinical trials. Previous articles have described that economic incentives and the absence of proper coordination can lead to fragmentation of resources and efforts, resulting in underpowered studies, prioritizing quantity over quality [18, 20]. In global health crises these issues exacerbate economic and health disparities, especially affecting LMIC [36–38]. Distribution of vaccines is the most studied example of this [39], but our findings also point identified insufficient knowledge sharing between the Global North and the Global South as a way inequalities are exacerbated during accelerated research [36].

Taking the theoretical framework of epistemic injustice [40, 41], we argue that acceleration of clinical trials, when done without proper coordination and inclusion of global, can have unjust epistemic consequences that harm LMIC and marginalised populations. Epistemic injustice refers to the wrongs done to someone in the processes of knowledge generation, exchange or use [41]. Our study suggests that when trials are driven by commercial interests rather than public health needs, the resulting research may overlook critical health issues pertinent to LMIC and/or disadvantaged populations. In recent years, the neoliberal model of globalisation and the marketisation of pharmaceutical clinical research has reduced the ability of LMIC national governments to establish research priorities and lead complex studies [42], such as accelerated clinical trials. Since these regions are a nonprofitable market economically, there are few financial incentives to accelerate trials which makes them more vulnerable to becoming merely a means for researchers (as data collection extraction sites, for instance) from affluent nations and large multinational pharmaceutical companies and not active contributors and benefactors of accelerated research. Furthermore, what is recognized and prioritized as a ‘global’ health emergency is often framed by Global North institutions, shaping which health issues are accelerated and which are neglected. All of this can make LMICs bear the burden of research studies without reaping the benefits, or contributing to scientific discussions [36–38], which intensifies the already operating economic, and epistemic injustices between the Global North and the Global South.

Accelerated clinical trials have a tendency to exacerbate issues that arise in all trials, such as sample representativeness. While our experts recognised that the inclusion of certain vulnerable participants is especially hard in accelerated clinical trials, the challenges related to the recruitment of participants belonging to marginalised groups such as ethnic minorities were not discussed. Inclusion of these groups requires more time and efforts due to additional recruitment strategies or lack of participant awareness [43] which can be too time consuming for accelerated trials. However, excluding vulnerable and marginalised groups can limit the data on potential side effects [43–45] exacerbating health disparities. Also, there is a risk that involving these groups in poorly designed or rushed studies may cause long-term harm to public trust in clinical research, particularly in communities that already with low engagement with research [43–45]. Furthermore, it can harm trust in clinical research [24, 44, 46]. Trust has a central role in clinical research: public acceptance of biomedical and clinical interventions and products is indispensable to ensure sustainable results [10]. One of the main aims of both research ethics and integrity is to promote trustworthiness, that is, to ensure that researchers and institutions behave in ways that justify public trust, which in turn helps maintain and strengthen public trust in clinical research [12, 47]. This can be achieved by ensuring the robustness of clinical trials implementation - even in emergency situations. Our experts recognized the importance of public trust during the COVID-19 pandemic, aligning with other authors who have emphasized public communication and trust as essential for the acceptance of new therapeutics [20, 21]. But trust is also linked to relevance and epistemic value: in order to maintain and gain societal trust in research, society must feel that the knowledge and advancements produced by it will be of benefit for them [10]. In situations of emergency and global crises, this dependent trust-relationship between the general public and the scientific community is even more at stake, due to a climate of panic and fear, spread of misinformation and general feelings of uncertainty [48].

Recommendations

The experts’ recommendations relate to the idea of accelerating clinical trials through dialogue and collaboration making special efforts to include those parties that have been traditionally excluded from research. This represents a fundamental shift in the way clinical research is being accelerated, particularly during global health emergencies like the COVID-19 pandemic. Experts called on funders and global governance organisations to make the general public and representatives from LMIC actively represented in accelerated trials. Moving from an industry-focused approach to one centred on patients and communities, would help to address challenges like participant recruitment, sample diversity, public trust, and inequalities in setting research priorities. While participation processes may be time consuming, it can be feasible and beneficial for accelerated trial pathways [48, 49]. Firstly, pre-existing literature shows that including patients and research participants in the trial design can improve participants retention and transparency in informed consent [50]. Secondly, public involvement and engagement of LMIC stakeholders voices can increase public trust in clinical research [25, 26] and avoid exacerbating existing global geographical inequalities [49]. Furthermore, early preparedness and long-term planning are needed to make the inclusion of patients, participants, and LMIC stakeholders feasible and effective in the context of accelerated trial pathways. Lastly, building relationships of trust through inclusivity could cultivate epistemic democracy and plurality, which could be of great benefit for research institutions, the general public, and clinical researchers [51]. Thus, this strategy can contribute to filling a hermeneutical epistemic gap in researchers and other clinical trial experts’ knowledge [49] as well as contribute to stopping forms of historical epistemic injustices [40].

Limitations and future lines of research

This study has several limitations. First, the experts were based in the Global North even though Global South voices can be especially relevant when issues and potential solutions of expedited research are discussed. Second, patients and research participants were not included in our sample, as the study focused on key stakeholders involved in the regulation, design, implementation, and publication of clinical trials as professionals. This reflects the specific scope and target population of the research. Including patients and research participants would require a broader research question exploring the lived experiences of research participation, as well as a different topic guide (it is difficult for those without professional training related to accelerated clinical trials to think of challenges experienced in terms of RE and RI challenges, indeed it is sometimes even difficult for those with professional training) and recruitment. This would be a valuable focus of a future study. Third, the recruitment via the professional networks of the authors, may have introduced bias. Although we invited 192 experts, those who accepted might be more sensitive to, or concerned about, ethical and integrity issues in clinical research, which might over-represent the level of reflection and concern for the challenges identified within the target group. At the same time, participation by those more able to reflect on the issues provides important, practice-informed, insights into specific RE/RI challenges related to accelerated clinical trials. Fourth, the questions of the 35 min long interviews were designed to fit experts’ busy schedules, which limited the depth of exploration of complex topics, such as potential ethical benefits of accelerated research. Finally, while our study offers important insights, it is also shaped by the limitations of participant recruitment. Despite extensive outreach to 192 individuals, only 25 agreed to participate, and we were unable to secure interviews with experts from key institutions such as the European Commission and the WHO. This reflects the challenges of accessing high-level decision makers and the extensive efforts that were made to recruit the purposive sample of 25 experts.

Conclusion

This study provides insights on the most relevant research ethics and integrity challenges associated with accelerated clinical trials. These challenges go beyond ethics approval by RECs. In fact, in the field of clinical trials in general, and of accelerated clinical trials specifically, research ethics and integrity are intimately and inevitably entangled with epistemic, social and justice matters. Furthermore, attention should be paid to social and epistemic considerations in clinical trials; without joined and coordinated efforts, robust and sound methodologies and open and transparent communication, accelerated clinical trials will not be as impactful as they could be. Thus, the relevance of research and trustworthiness of trials in emergency times becomes even more central, not only in highly needed therapeutics and vaccines, but also in progressing towards a landscape of socially and epistemically just clinical research. To do that, many more parties, including representatives of unprivileged geographical areas and research participants’ representatives, should be included in the decision-making processes related to accelerated clinical trials.

Authors’ contributions

CPP, LE, HJ, MvdH, NE: conceptualized and developed the study protocol. CPP, LE, HJ, SH, MG, NE: participant recruitment. CPP, LE: data collection. CPP, GI, NE: data analysis. CPP, GI, LE, HJ, SH, MG, MvdH, NE: drafted, reviewed and approved final manuscript.

Funding

This paper was supported by the PREPARED project funded by the European Union under the grant agreement No 101058094.

Data availability

The datasets generated and analysed during the current study are not publicly available due to ensuring participants’ privacy but are available, always protecting participants’ privacy and anonymity, from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study did not suppose any risk for participants, and it was performed in line with the principles of the Declaration of Helsinki. The study was performed in accordance to institutional regulations at the Vrije Universiteit Amsterdam. The self-check procedure of the Research ethics review committee of the Faculty of Science of the Vrije Universiteit Amsterdam (BETHCIE) was passed and approved to this study. In this self-check a series of questions is used to determine whether your research complies to the Code of Ethics for Research involving Human Participants Faculty of Science. The study did conform to this code, and further review by the BETHCIE was not required. Additionally, all participants filled out an informed consent online form and received written and oral information about the study.

Consent for publication

All authors five their consent to publish this manuscript. All the participants gave their informed consent to have the results published.

Competing interests

The authors declare no competing interests.