Informed consent (IC) is a legal and ethical cornerstone in clinical research involving humans. While it embodies the principle of decisional autonomy, its implementation faces significant challenges.
Objectives
This narrative review aims to critically analyse the ethical, legal and regulatory aspects of IC in clinical research, with a specific focus on UK and European Union (EU) jurisdictions. Particular attention is given to medico-legal defensibility, the treatment of vulnerable populations and the emerging forensic implications of consent-related failures.
Methods
Key international instruments (Declaration of Helsinki, Council for International Organizations of Medical Sciences Guidelines), UK statutes (Mental Capacity Act 2005, Human Tissue Act 2004) and data protection regulations (Regulation (EU) 2016/679 (EU GDPR) and its post-Brexit counterpart, the UK GDPR) were examined alongside relevant case law. Empirical findings, audit reports and forensic literature were integrated to assess procedural vulnerabilities and regulatory expectations.
Results
The review identifies major risks associated with invalid or poorly documented consent, including therapeutic misconception, capacity fluctuation and coercion in hierarchical or cross-cultural contexts. It highlights the increasing role of forensic medicine in assessing consent adequacy and outlines innovative models such as dynamic and electronic consent, evaluating their medico-legal relevance.
Conclusions
Robust, participant-centred consent frameworks are essential to uphold ethical integrity and legal compliance in clinical research. Regulatory harmonisation, institutional preparedness and forensic awareness are critical to mitigating liability, safeguarding participant rights and maintaining public trust in biomedical science.
Council for International Organizations of Medical Sciences (CIOMS). International ethical guidelines for health-related research involving humans. Geneva: CIOMS, 2016.
3.
UK Parliament. Mental Capacity Act 2005. c.9.
4.
UK Parliament. Human Tissue Act 2004. c.30.
5.
European Parliament and Council. Regulation (EU) 2016/679 of the European Parliament and of the Council on the protection of natural persons with regard to the processing of personal data and on the free movement of such data (General Data Protection Regulation). OJ L 119, 4 May 2016. Available at: https://eur-lex.europa.eu/eli/reg/2016/679/oj (accessed 18 April 2025).
Montgomery v Lanarkshire Health Board [2015] UKSC 11.
12.
UK Health Research Authority. Guidance on applying ethical principles in research. 2023. https://www.hra.nhs.uk/.
13.
GradyC. Enduring and emerging challenges of informed consent. N Engl J Med2017; 376: 856–867.
14.
Council of Europe. Convention for the Protection of Human Rights and Fundamental Freedoms. Council of Europe Treaty Series 005, Council of Europe, 1950.
15.
Re T (Adult: Refusal of Medical Treatment). [1992] EWCA Civ 18; [1993] Fam 95 (CA).
16.
UK Parliament. Equality Act 2010, c.15, Section 149. London: The Stationery Office, 2010.
17.
United States Government. Trials of war criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Vol 2. Washington, DC: US Government Printing Office, 1949.
18.
HarknessJLedererSEWiklerD. Laying ethical foundations for clinical research. Bull World Health Organ2001; 79: 365–366.
19.
JacobsNTinnerholm LjungbergH. How ethics travels: the international development of research ethics committees in the late twentieth century. Eur J Hist Med Health2021; 78: 257–265.
20.
UK Health Research Authority (HRA). Official website. https://www.hra.nhs.uk/ (accessed 18 April 2025).
21.
Bolam v Friern Hospital Management Committee [1957] 1 WLR 582. Queen’s Bench Division (England and Wales).
UK General Medical Council (GMC). Official website. https://www.gmc-uk.org/ (accessed 18 April 2025).
25.
GradyCCummingsSRRowbothamMC, et al.Informed consent. N Engl J Med2015; 372: 856–863.
26.
Ha DinhTTBonnerAClarkR, et al.The effectiveness of the teach-back method on adherence and self-management in health education for people with chronic disease: a systematic review. JBI Database Syst Rev Implement Rep2016; 14: 210–247.
KamuyaDMTheobaldSJMarshV, et al.The one who chases you away does not tell you go: silent refusals and complex power relations in research consent processes in coastal Kenya. PLoS One2015; 10: e0126671.
29.
TindanaPOKassNAkweongoP. The informed consent process in a rural African setting: a case study of the Kassena-Nankana district of northern Ghana. IRB2006; 28: 1–6.
30.
KerriganSErridgeSLiaquatI, et al.Mental incapacity in patients undergoing neuro-oncologic treatment: a cross-sectional study. Neurology2014; 83: 537–541.
31.
MarsonDCMartinRCTriebelKL, et al.Capacity to consent to research participation in adults with malignant glioma. J Clin Oncol2010; 28: 3844–3850.
32.
TriebelKLMartinRCNaborsLB, et al.Medical decision-making capacity in patients with malignant glioma. Neurology2009; 73: 2086–2092.
33.
General Medical Council. Good medical practice. London: GMC, 2024, Section 82: Consent and capacity.
34.
UK Parliament. Medicines for Human Use (Clinical Trials) Regulations 2004, SI 2004/1031, as amended. London: The Stationery Office, 2004. Available at: https://www.legislation.gov.uk/uksi/2004/1031/contents/made (accessed 18 April 2025).
35.
ChatfieldKSchroederDGuantaiA, et al.Preventing ethics dumping: the challenges for Kenyan research ethics committees. Res Ethics2021; 17: 23–44.
European Commission. Ethics and data protection in Horizon 2020. Version 6.1, July 2019.
39.
U.S. Department of Health and Human Services. 45 CFR 46 (Common Rule). Revised 2018.
40.
UK Research and Innovation (UKRI). Official website. https://www.ukri.org/ (accessed 18 April 2025).
41.
Health Research Authority (HRA). Spectrum 10K update – 20 May 2022 (REC reconsideration; study paused). London: HRA, 2022.
42.
Health Research Authority (HRA). Research Ethics Committee – standard operating procedures (Version 7.7; effective 11 April 2025) – procedure for review and possible suspension/termination of favourable opinions. London: HRA, 2025.
43.
Health Research Authority (HRA). GDPR transparency wording for all sponsors (templates; last updated 4 April 2025). London: HRA, 2025.
44.
Information Commissioner’s Office (ICO). International transfers: a guide (UK GDPR rules on restricted transfers; transparency about third-country transfers). Wilmslow: ICO, 2023–2024.
RowbothamMCAstinJGreeneK, et al.Interactive informed consent: randomized comparison with paper consents. PLoS One2013; 8: e58603.
47.
NishimuraACareyJErwinPJ, et al.Improving understanding in the research informed consent process: a systematic review. BMC Med Ethics2013; 14: 28.
48.
KayeJWhitleyEALundD, et al.Dynamic consent: a patient interface for twenty-first century research networks. Eur J Hum Genet2015; 23: 141–146.
49.
Budin-LjøsneITeareHJKayeJ, et al.Dynamic consent: a potential solution to some of the challenges of modern biomedical research. BMC Med Ethics2017; 18: 4.
