By: ABRS- Clinical Insights Team
Abstract
Informed consent is a fundamental ethical and legal requirement in clinical research, ensuring that participants are fully aware of the risks, benefits, and procedures associated with their involvement. Despite its importance, the consent process continues to face challenges, including overly complex documents, cultural and linguistic barriers, and misconceptions about therapeutic benefit. Recent innovations, such as electronic informed consent (eConsent), health literacy–based communication strategies, and patient involvement in the design of consent materials, have been introduced to address these limitations. This article reviews the ethical and regulatory foundations of informed consent, identifies ongoing challenges in practice, and highlights technological and methodological innovations that aim to strengthen participant autonomy, trust, and comprehension in modern clinical trials.
Introduction
Informed consent has long been considered a cornerstone of ethical clinical research. It provides the foundation for respecting participant autonomy by ensuring that individuals understand the potential risks, benefits, and obligations associated with their decision to participate. However, despite decades of guidance from international ethical codes and regulatory authorities, the consent process remains one of the most debated aspects of clinical trial design and execution.
Traditional consent forms are often lengthy, complex, and filled with medical or legal jargon that can overwhelm participants. As a result, individuals may sign documents without fully comprehending the nature of the study or the implications of their participation. This issue is compounded by cultural and linguistic differences that can affect how information is understood, creating inequities in participant access and representation.
In recent years, the clinical research community has begun to recognize that informed consent should not be reduced to a signed form but rather understood as a dynamic, ongoing process of communication. Regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the International Council for Harmonisation (ICH) have emphasized the importance of clarity, cultural sensitivity, and participant-centered approaches in their updated guidance (Food and Drug Administration, 2023; International Council for Harmonisation, 2016). At the same time, technological innovations such as eConsent platforms and interactive multimedia tools are being adopted to improve comprehension and enhance participant autonomy.
This article explores the ethical and regulatory framework of informed consent, examines persistent challenges in current practice, and discusses innovative approaches and future directions aimed at making the consent process more transparent, inclusive, and effective.
Ethical and Regulatory Framework of Informed Consent
Informed consent is a cornerstone of ethical clinical research. It is not only a legal requirement but also a moral obligation to ensure that participants fully understand the risks, benefits, and procedures involved in a study. Its foundation lies in international standards such as the Declaration of Helsinki, which states that research involving human subjects must respect individual autonomy and guarantee that participation is voluntary and based on adequate information (World Medical Association, 2013).
In recent years, regulatory agencies have reinforced these ethical principles. The U.S. Food and Drug Administration (FDA), for instance, issued updated guidance in 2023 directed at sponsors, institutional review boards (IRBs), and investigators. This document emphasizes the importance of providing consent forms that are clear, concise, and adapted to the cultural and educational background of participants, highlighting that signing a document is insufficient if comprehension is not achieved (Food and Drug Administration, 2023).
In addition, the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines remain the global reference standard. The 2016 update (E6 R2) underscores that information given to participants must be accurate, complete, and presented in a manner that allows sufficient time for decision-making (International Council for Harmonisation, 2016). This reinforces the idea that informed consent should be understood as a dynamic process rather than a one-time administrative requirement, placing transparency and effective communication at the center of ethical research practices.
Challenges in Current Practice
Despite its central role in safeguarding participant autonomy, informed consent continues to face significant challenges in clinical research. One of the most persistent problems is the complexity of consent documents. Studies have shown that many forms are written at a reading level too advanced for the average participant, filled with medical and legal jargon that hinders true comprehension (Menikoff & Kaneshiro, 2021). This results in patients often signing documents without fully understanding the study’s scope, risks, or their rights as participants.
Cultural and linguistic barriers further complicate the process. Research indicates that participants from minority and non-English-speaking backgrounds frequently encounter difficulties when reviewing consent forms, as translations may not fully capture cultural nuances or key concepts (Kass et al., 2022). This gap can lead to misinterpretation of the information provided and, in some cases, to lower participation among underrepresented populations in clinical trials.
Another recurring issue is therapeutic misconception, where participants mistakenly believe that enrolling in a clinical trial guarantees direct personal benefit. This misunderstanding has been documented across multiple therapeutic areas and highlights the difficulty of balancing optimism with realistic expectations during the consent process (Appelbaum et al., 2020).
Additionally, operational challenges—such as limited time for investigators to discuss consent, high patient volumes, and lack of training in communication—can turn informed consent into a procedural formality rather than an ethical dialogue. These issues underscore the need for strategies that simplify, humanize, and adapt the consent process to diverse populations while ensuring compliance with ethical standards.
The Role of Technology in Enhancing Participant Autonomy
Beyond improving comprehension, technology has also become a tool for strengthening participant autonomy in clinical trials. Digital platforms provide participants with greater flexibility to review information at their own pace, revisit materials when needed, and even ask questions asynchronously. This contrasts with traditional paper-based consent, which often occurs under time constraints during a clinical visit (Miller & Mello, 2020).
Mobile applications and secure web portals allow participants to access multimedia explanations, frequently asked questions, and real-time support. This not only increases convenience but also empowers individuals to make decisions more independently. According to a systematic review, participants using eConsent platforms reported higher satisfaction and a stronger sense of control over their participation compared with those using traditional methods (Karahalios et al., 2022).
Additionally, electronic systems can enhance transparency and traceability. Features such as digital audit trails and timestamped confirmations ensure that the process is properly documented, reducing the risk of compliance issues for sponsors and investigators. At the same time, these records reinforce accountability, demonstrating that participants were adequately informed at each stage (Grady et al., 2021).
By integrating technology into the consent process, clinical research is moving closer to a model that prioritizes autonomy, flexibility, and participant empowerment—key elements for building trust in increasingly complex and globalized clinical trials.
Innovations and Future Perspectives
To address the limitations of traditional informed consent, researchers and regulators have increasingly embraced digital and interactive approaches. Electronic informed consent (eConsent) platforms, which integrate multimedia tools such as videos, infographics, and interactive quizzes, have been shown to improve participant comprehension and satisfaction compared with paper-based methods (Grady et al., 2021). These tools also allow for remote participation, an advantage that became particularly relevant during the COVID-19 pandemic, when physical access to clinical sites was restricted.
Another promising innovation is the incorporation of health literacy principles into consent form design. By simplifying language, structuring documents more clearly, and adapting content to the reading levels of participants, sponsors can significantly improve understanding. In a recent study, participants exposed to plain-language and shorter forms reported higher comprehension and greater confidence in their decision-making (Kass et al., 2022).
Moreover, there is growing interest in participant involvement in the design of consent processes. Patient advocacy groups and community advisory boards are increasingly invited to review consent forms and suggest improvements to ensure they reflect cultural and contextual realities. This participatory approach not only enhances clarity but also fosters trust and inclusivity in clinical research (Fung et al., 2020).
Regulatory agencies have also encouraged these innovations. The FDA’s 2023 guidance explicitly acknowledges the role of digital tools and stresses that consent must be viewed as an ongoing process of communication, not a single signed document (Food and Drug Administration, 2023). Moving forward, a combination of technology, health literacy strategies, and patient engagement is expected to reshape informed consent into a more dynamic, ethical, and participant-centered practice.
Conclusion
Informed consent remains one of the most critical ethical safeguards in clinical research. It protects participant autonomy, builds trust between researchers and participants, and ensures that the rights of individuals are respected throughout the research process. Yet, as this review highlights, significant challenges persist—ranging from overly complex documentation and cultural barriers to misconceptions about therapeutic benefits.
Recent developments offer promising solutions. Digital innovations such as electronic informed consent (eConsent), the integration of health literacy principles, and patient involvement in designing consent processes all represent meaningful steps toward improving comprehension and transparency. Moreover, regulatory guidance from organizations such as the FDA and ICH reinforces the importance of viewing informed consent as a continuous process of dialogue, not a one-time administrative task.
As clinical trials become increasingly global and complex, the evolution of informed consent will be essential for ensuring both ethical integrity and operational success. By combining regulatory oversight, technological tools, and patient-centered practices, the research community can foster a model of consent that is more accessible, equitable, and responsive to the needs of diverse populations. Ultimately, strengthening informed consent is not only about compliance—it is about honoring the trust that participants place in the scientific enterprise.
References
Appelbaum, P. S., Lidz, C. W., & Klitzman, R. (2020). Voluntariness of consent to research: A conceptual model. Hastings Center Report, 50(1), 40–47. https://doi.org/10.1002/hast.1089
Food and Drug Administration. (2023). Informed consent guidance for IRBs, clinical investigators, and sponsors. U.S. Department of Health and Human Services. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/informed-consent-guidance-irbs-clinical-investigators-and-sponsors
Fung, E. B., Guo, M., & Cooley, P. (2020). Patient and community engagement in the design of informed consent for clinical trials. Journal of Empirical Research on Human Research Ethics, 15(4), 279–288. https://doi.org/10.1177/1556264620923751
Grady, C., Cummings, S. R., Rowbotham, M. C., & McConnell, M. V. (2021). Digital tools for enhancing informed consent in clinical trials: A review. Clinical Trials, 18(5), 561–569. https://doi.org/10.1177/17407745211032741
International Council for Harmonisation. (2016). Integrated addendum to ICH E6(R1): Guideline for good clinical practice E6(R2). ICH Harmonised Guideline. https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf
Karahalios, A., Bhattacharya, S., & Milne, R. (2022). Electronic informed consent in clinical research: A systematic review. Journal of Clinical Epidemiology, 147, 76–86. https://doi.org/10.1016/j.jclinepi.2022.03.007
Kass, N., Taylor, H., King, P., & Cho, M. K. (2022). Cultural and linguistic challenges in informed consent for clinical research. The Journal of Clinical Ethics, 33(4), 221–229.
Menikoff, J., & Kaneshiro, J. (2021). Improving informed consent in clinical trials: The need for better comprehension. New England Journal of Medicine, 385(7), 603–606. https://doi.org/10.1056/NEJMp2102451
Miller, F. G., & Mello, M. M. (2020). The ethical challenges of electronic informed consent in clinical research. Journal of the American Medical Association, 323(5), 407–408. https://doi.org/10.1001/jama.2019.21663
World Medical Association. (2013). Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA, 310(20), 2191–2194. https://doi.org/10.1001/jama.2013.281053