Accommodating cultural differences in the International Conference of Harmonisation Good Clinical Practice guidelines

Introduction

The International Conference on Harmonisation (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use is a collaborative effort between regulatory authorities and the pharmaceutical industry to establish guidelines for pharmaceutical products. The ICH Good Clinical Practice (GCP) guidelines were implemented in 1997 to standardise the management of clinical trials. While intended to harmonise regulatory decision-making among ICH members—and used to guide research in low-income and middle-income countries (LMICs)—it has been argued that the ICH GCP guidelines were developed through informal consensus less rooted in scientific evidence. If GCP guidelines are truly meant to serve global interests, they must involve all relevant stakeholders, including researchers, sponsors, regulators, ethical reviewers and patients’ representatives, particularly those from LMICs. The absence of perspectives of LMIC researchers is perhaps one of the main critiques of these well-intentioned guidelines.

In LMICs, sociopolitical issues, poverty, healthcare inequities and a lack of public awareness are persistent issues that influence clinical research. Research participation is often a last resort for accessing treatment, introducing ethical dilemmas requiring careful consideration. An ‘integrated addendum’ was previously introduced to support less-resourced academic organisations. However, the updated document focused only on technological advancements and quality management. Thus, bridging the divide between existing international guidelines and their application to LMICs is increasingly important.

Bhutta calls for greater cultural sensitivity and equity-focused ethics. Others critique Western-centric approaches to research, advocate for decolonising research ethics and offer models that promote equitable partnerships. In light of this, our roundtable discussions (with 25 health professionals from LMICs and the UK, with diverse research experiences) identified the following seven key challenges, highlighting ICH GCP’s limitations in accommodating cultural, religious and social norms.

Informed consent

Collectivist culture dynamics do not typically accommodate autonomous decision-making, with families significantly guiding individual choices. In LMICs, these challenges are exacerbated by stigma and a lack of awareness about the significance of research. Alternative pathways to written informed consent could be considered to better accommodate deep-rooted cultural norms.

Sociocultural differences

Pervasive mental health stigma in LMICs makes it challenging to recruit participants in overcrowded public hospitals where confidentiality is seldom accommodated. Many fear being ‘seen’ by relatives or friends and want to avoid bringing ‘shame’ to their family. With the added component of multifaceted decision-making involving gatekeepers and family members, maintaining anonymity and privacy becomes a greater challenge. In essence, confidential spaces remain a crucial element to ensuring participants’ ethical engagement and voluntary consent.

Illiteracy and lack of awareness

Participants are often recruited from hospitals, facilitated by local community representatives. However, external ethical committees encourage advertising for potential participants, which is complicated by illiteracy in LMICs (i.e, potential participants cannot read or understand recruitment adverts). External ethical review boards also require consent from participants instead of caregivers. We advise that external ethics boards should perhaps consider feedback from local ethics committees for a better understanding of the local cultural challenges which are unique to LMICs.

Protecting the privacy of minors

LMIC researchers encounter difficulties with recruiting minors without dedicated legal guardians to provide consent. With no access to local ethics committees in such areas, it is arduous to meet participants’ needs while adhering to the consent guidelines of the approving institution board. It is important for children with abusive parents or without legal guardians to be safely provided with access to research. Here, communal culture is construed as a solution, as trusted community leaders may be able to provide proxy informed consent.

Community engagement

The term ‘community engagement’ requires further clarification to be implemented more ethically as a holistic framework; however, it can be a promising approach to addressing ethical challenges in low-income settings. For example, involving patients to comment on ethics applications would give them ownership and create employment for people with mental illnesses.

Communication and trust

Establishing a connection between researchers and participants is integral to cultivating an environment of mutual respect and trust. Being mindful of attire is important to make participants feel comfortable. For instance, community researchers in Pakistan have observed that participants showed a decreased level of trust when researchers were dressed in primarily Western clothing.

Data protection

Community health workers are often poorly paid and detached from the wider impact of research and how it informs policymaking. We need to invest more funds in training these workers and perhaps incentivise their role. Local ethics committees also fail to hold accountability and allocate only a brief section to data management in ethics applications. These are not abstract problems; they have an impact on ethical research practices. What emerges from our discussions is a call for the contextualisation of ICH-GCP. Many researchers may argue against the adaptation of the ICH GCP guidelines, citing the risk of compromising the quality of clinical trials and diluting the ethical standards; however, a strict applicability carries greater ethical cost, mistrust, inequity and exclusion of vulnerable populations. We recommend a consistent partnership and open communication between local and external authorities to incorporate balanced perspectives and harmonise rules for clinical trials. There is a need for research guidelines to be flexible and inclusive of vulnerable populations, particularly in the context of poverty and healthcare inequities that amplify the difficulties in LMICs.

Conclusion

Our findings from the roundtable discussion are not a criticism of the GCP framework—decolonising research ethics means more than critique and demands collective efforts. The ICH GCP guidelines, now nearly three decades old, must evolve—not simply through technological addenda, but through a paradigm shift that puts varying sociocultural sensitivities and norms at its core. Otherwise, the ICH GCP guidelines will remain based only on Western clinical research experiences and will still largely be unrepresentative of the challenges LMIC researchers face in practising ethics and good governance. Future discussions should be more diverse and adopt more structured consensus-building methods to generate a reliable group consensus on a culturally relevant ethical framework for LMICs.

Ethics statements

Patient consent for publication
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Ethics approval
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Acknowledgments

This paper is being submitted on behalf of all discussion group participants as coauthors of the manuscript.

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