Informed consent in clinical research: Medico-legal standards,ethical challenges and forensic implications in UK and EU frameworks

Abstract

Background

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.

Keywords

Informed consent IC clinical research medico-legal risk GDPR mental capacity bioethics forensic medicine

Introduction

The ethical and legal legitimacy of clinical research involving humans rests fundamentally upon the principle of informed consent (IC). More than a procedural formality, IC operates as a manifestation of the participant's right to autonomy, enshrined in international ethical frameworks^1,2 and in UK statutes.^3,4

In the European Union, the General Data Protection Regulation (GDPR, Regulation (EU) 2016/679) further reinforces the necessity of lawful and transparent processing of personal data in health research contexts.^5,6

While the normative foundations of IC are well established, their operationalisation within diverse research settings remains complex. Investigators must not only ensure the provision of adequate information and comprehension but also attend to contextual factors such as fluctuating decision-making capacity, cultural variability in the perception of autonomy and potential therapeutic misconception.⁷ These challenges are particularly salient in research involving vulnerable populations or conducted in resource-limited or emergency settings.⁸

This review critically examines the ethical, legal and procedural considerations in obtaining IC for research participation, with particular emphasis on the intersection between international ethical norms and jurisdiction-specific legal obligations. By analysing key barriers to valid consent and exploring emerging consent models, this paper aims to contribute to the development of ethically robust and legally compliant research practices.

This review is particularly relevant to medico-legal practitioners, research ethics boards and policy-makers engaged in the adjudication of research compliance, especially given the growing forensic scrutiny over consent-related procedures.

The importance of IC in clinical research

IC affirms the participant's right to autonomy and ensures that enrolment in a research protocol is voluntary, informed and lawfully documented. From a legal standpoint, failure to obtain valid consent may render a clinical research unlawful, exposing investigators and institutions to claims of battery, negligence or breach of statutory duty.⁹

Ethically, the consent process is grounded in the principles of respect for people, beneficence and justice, as articulated in key international instruments.^1,2 While these principles were famously codified in the USA through the Belmont Report,¹⁰ in the UK the Report holds persuasive rather than normative value, with statutory and case law sources – such as the Mental Capacity Act 2005 and the Montgomery judgment^3,11 – providing the binding framework. These principles collectively require that participants be provided with clear, relevant information about the research objectives, risks, potential benefits and their rights – including the right to withdraw at any time without reprisal.¹²

The legal function of IC also intersects with data protection legislation, particularly under the GDPR, which classifies consent as one of the lawful bases for processing personal data in health research.⁵ Accordingly, investigators must not only ensure that participants understand the nature of the study, but also provide specific and unambiguous consent for data use, in line with the aforementioned Articles 6 and 9 of the GDPR.

In practical terms, IC contributes to procedural transparency and fosters public trust in research institutions. It serves to reduce power asymmetries between investigators and participants, especially in vulnerable groups where capacity to consent may be impaired or contextually constrained.⁸ However, it must be recognised that a formalistic approach to consent – centred solely on documentation – may undermine its ethical intent. Validity depends not only on the presence of a signature but on the presence of comprehension, voluntariness and contextual sensitivity.¹³

Consequently, IC should not be viewed as a static or perfunctory requirement, but rather as a dynamic and ethically integrated process that underpins the legitimacy and social acceptability of clinical research.

Ethical foundations of IC

The ethical foundations of IC are articulated through three inter-related principles: respect for autonomy, beneficence and justice.

Respect for autonomy

Respect for autonomy underpins the very concept of IC.

In legal terms, in the EU autonomy is protected under Article 8 of the European Convention on Human Rights, which guarantees the right to private life, including bodily and informational self-determination.¹⁴

In UK Law, the Mental Capacity Act 2005 codifies the presumption of capacity and the principle that individuals have the right to make unwise or unconventional decisions, provided they are competent to do so.³ The 1992 landmark case Re T (Adult: Refusal of Medical Treatment¹) reaffirmed the primacy of personal autonomy, even where the individual's decision may conflict with clinical advice.¹⁵

Applied to research, this means that consent must not only be informed and voluntary but must also be free from coercion, manipulation or undue influence.

Beneficence

The principle of beneficence requires that investigators act in the best interest of participants, aiming to maximise potential benefits and minimise foreseeable harms. Ethically, this derives from the Belmont Report¹⁰ and is reinforced in the Declaration of Helsinki, which mandates that the welfare of the subject must take precedence over the interests of science or society.¹

While beneficence is less explicitly codified in UK legislation, it permeates common law duties of care. In research, failure to disclose foreseeable risks may give rise to liability under the tort of negligence. This legal shift towards participant-centred disclosure reflects the reasoning in Montgomery v Lanarkshire Health Board,² which has also been referenced in research ethics debates regarding material risk communication and information tailoring.

Therefore, ethical consent is not achieved merely by procedural disclosure, but by ensuring risk information is material, contextualised and comprehensible – particularly where participation may involve physical, psychological or social harm.¹¹

Justice

The principle of justice demands fairness in the distribution of research burdens and benefits. It obliges investigators to avoid the exploitation of vulnerable or marginalised populations, and to ensure that inclusion and exclusion criteria are ethically and scientifically justified.

In legal terms, equality and non-discrimination obligations derive from section 149 of the Equality Act 2010¹⁶ and Article 14 of the European Convention on Human Rights.¹⁴ Investigators must ensure that vulnerable groups (e.g. children, elderly, individuals with disabilities, non-native speakers) are not included solely due to the ease of access or institutional convenience.

Ethically, justice extends to community-level considerations in global research contexts. In settings where individual autonomy is mediated by collective decision-making, investigators must navigate context-sensitive consent models that do not undermine fundamental rights while respecting local governance structures.⁸

History and development of IC in clinical research

IC in clinical research has evolved through a complex interplay of ethical outrage, legal codification and institutional reform. Historically, its development reflects a progressive recognition of the participant not as a passive object of study but as a rights-bearing individual entitled to agency, dignity and legal protection.

From violations to codification: the Nuremberg legacy

The modern doctrine of IC was formally articulated in the Nuremberg Code (1947), a direct response to the medical atrocities committed by Nazi physicians during the Second World War.¹⁷ The Code's first principle established consent as a non-derogable condition for lawful human experimentation. Though not legally binding per se, the Code influenced subsequent ethical frameworks and case law.

In the UK, the Code catalysed greater attention to research oversight, particularly in light of emerging post-war biomedical developments.^18,19 However, its absolutist formulation left unresolved questions regarding capacity, coercion and cultural norms.

The Declaration of Helsinki and procedural normativity

The World Medical Association's Declaration of Helsinki (first adopted in 1964, revised multiple times) provided a more nuanced and flexible formulation of IC, accommodating modern clinical realities.¹ Notably, it introduced provisions for proxy consent in cases of inability, the obligation to communicate risks and the primacy of participant welfare over scientific interests.

The UK's incorporation of the Declaration of Helsinki principles is evident in the procedures of Research Ethics Committees (RECs) and in the national guidance issued by the Health Research Authority (HRA).²⁰ In legal disputes, while the Declaration lacks formal status in UK Law, it has been cited as persuasive authority in cases involving the ethical conduct of research and clinical innovation.⁹

Case law and statutory milestones in UK jurisprudence

The evolution from Bolam v Friern Hospital Management Committee³ ²¹ to Montgomery⁴ ¹¹ marks a shift from a paternalistic standard of disclosure to a participant-centred, material risk-based model.

Although Montgomery concerned treatment, the reasoning is applicable to research settings, especially where participation carries foreseeable risks or therapeutic ambiguity. Furthermore, the Mental Capacity Act 2005 provided a statutory framework for determining and supporting decision-making capacity, including for research participants lacking capacity, under sections 30–34.³

Parallel developments, such as the Human Tissue Act 2004, further codified consent as a lawful pre-condition for the storage and use of human biological materials in research.⁴ In the context of data, the GDPR imposes heightened transparency requirements and lawful basis for data processing, with consent playing a central but complex role in health research.⁵

Effective implementation of IC requires not only guidance but enforceable oversight mechanisms. In the UK, this is provided through:

RECs which review consent procedures and assess their proportionality;

HRA which issues national policy guidance and monitors compliance;

Medicines and Healthcare products Regulatory Agency (MHRA)²² which conducts Good Clinical Practice inspections²³;

General Medical Council (GMC) which may initiate fitness-to-practice proceedings in cases of professional misconduct.²⁴

Global and regulatory expansion

At the international level, ethical oversight mechanisms – such as Institutional Review Boards (IRBs), RECs and the Council for International Organizations of Medical Sciences (CIOMS guidelines)² – have institutionalised IC as a procedural and ethical norm. Yet, divergence remains in application: low–mid-income countries often face tensions between Western autonomy-based consent models and communal or hierarchical decision-making traditions.⁸

Contemporary challenges, including genomic research, digital platforms and emergency trials, continue to test the elasticity of the established consent norms. These evolving contexts call for consent models that are legally robust, ethically grounded and operationally adaptable.

Essential components of IC

IC is not a singular document but a process defined by a set of essential conditions that must be cumulatively satisfied for it to be considered valid. UK case law, statutory provisions and international ethical frameworks converge in identifying four interdependent components: adequate information, genuine comprehension, voluntary decision-making and ongoing consent.

Adequate information disclosure

The first requirement is that participants are provided with sufficient, relevant and accurate information regarding the research protocol. This includes, at minimum:

The purpose and design of the study.

Anticipated risks and benefits.

Alternative options, if any.

Data processing practices, including confidentiality safeguards.

The right to withdraw.

Under the Montgomery standard,¹¹ now the dominant doctrine in UK consent law, the investigator must disclose information that a reasonable person in the participant's position would find material. The ruling, though developed in the clinical context, is directly applicable to research participation when risks and uncertainties are involved.

Further, Article 13 of the GDPR requires that participants be informed of how their personal data will be processed, which imposes additional obligations in the context of health research.⁵

The Declaration of Helsinki and HRA Guidance also emphasise clarity and accessibility in information provision, including the use of plain language and adapted formats for low-literacy populations.^1,12

Comprehension

Comprehension is a distinct legal and ethical requirement. The provision of information is insufficient unless the participant actually understands the nature and implications of their involvement.

Under UK Law, the Mental Capacity Act 2005 (section 3) stipulates that a person is deemed to have capacity if they can understand, retain and weigh the relevant information and communicate a decision.³

Ethically, the CIOMS Guidelines state that IC must be based on demonstrable understanding, not merely formality.² Empirical studies indicate that mere distribution of standardised forms fails to ensure comprehension, particularly in marginalised populations or where complex scientific terminology is used.²⁵

Techniques such as the ‘teach-back’ method – where participants are asked to re-state the information in their own words to confirm comprehension – together with interactive discussion and multi-media tools, are recommended in complex or high-risk studies, especially where therapeutic misconception may confound understanding.^7,26

Voluntariness and absence of coercion

Voluntariness implies the freedom to decide without undue influence, coercion or manipulation. This aspect is particularly delicate in hierarchical settings (e.g. care homes, prisons, military environments) or in contexts of economic dependence, such as low-income communities where research participation may be incentivised.

The Nuremberg Code and subsequent ethical instruments require that consent be ‘free power of choice, without force, fraud, deceit, duress, or other forms of constraint’.¹⁷

From a legal perspective, the UK courts have recognised the invalidating effect of coercion on consent, as seen in Re T (Adult: Refusal of Medical Treatment) [1992],¹⁵ which held that undue pressure from a third party (in that case, a parent) could render a decision legally void.

Investigators must document the context in which consent is obtained, and where appropriate, assess power asymmetries and cultural dynamics that may influence voluntariness.⁸

Ongoing consent and the right to withdraw

IC is not a one-time transaction but a dynamic ethical and legal obligation throughout a research's lifecycle. Participants must be regularly reminded of their right to withdraw and be informed of any new findings or changes that may affect their willingness to continue.

The Declaration of Helsinki mandates the provision of updated information to participants and the re-consenting process where appropriate.¹

In UK research governance, the HRA requires that withdrawal procedures be explicitly stated and operationalised in consent forms and protocols.¹²

Legally, the Human Tissue Act 2004 (section 2) enshrines the principle that consent must be ‘appropriate and in place at the time of use’, which implies continuing relevance rather than a static document.⁴

GDPR's Article 7(3) reinforces this principle by stating that ‘the data subject shall have the right to withdraw consent at any time’, and such withdrawal must be as easy as giving it.⁵

Challenges and ethical dilemmas in IC practice

Despite the normative clarity surrounding IC, its implementation in clinical research is often complicated by real-world conditions that undermine ethical ideals and legal validity. This section explores three critical domains in which the IC process is particularly vulnerable: emergency contexts, cross-cultural communication and diminished decision-making capacity.

Emergency research: the consent exception and its limits

In emergency settings, such as intensive care units or pre-hospital research, patients may lack capacity due to unconsciousness or altered sensorium, and the window for enrolment is often narrow. Under such circumstances, ethical frameworks and UK Law allow for exceptional waivers or deferred consent mechanisms.

The Mental Capacity Act 2005 (sections 30–34) permits research involving incapacitated adults only if:

the research is approved by an appropriate body (e.g. REC);

it relates to the condition affecting the person;

it entails minimal risk and burden.³

Moreover, proxy consent from a personal or nominated consultee is required unless the intervention is urgent.

However, audit reports from National Health System (NHS) Trusts and MHRA inspections have identified repeated failures to properly document re-consent procedures when patients later re-gained capacity, rendering the initial authorisation ethically and potentially legally invalid.²⁷

Cultural barriers and misaligned assumptions

In multi-cultural or global research contexts, IC may be undermined by culturally embedded deference, such as participants showing respect and compliance towards physicians, elders or community leaders, rather than exercising independent decision-making,^8,28 language barriers and different conceptions of autonomy.

For example, in some collectivist communities – both in the UK and internationally – decision-making is often delegated to family or community leaders, challenging the Western model of individualised consent. Furthermore, concepts such as ‘refusal’ or ‘withdrawal’ may be linguistically or socially constrained.

In the case of Kassena-Nankana District (Northern Ghana), empirical work documented how household heads and community leaders mediated decision-making about research participation.²⁹ Related community-based studies subsequently described ‘silent refusal’ – often manifested as what might be termed ‘silent non-cooperation’, non-overt dissent expressed through non-cooperation – complicating explicit verbal refusal.²⁸ In the UK, similar phenomena may arise among refugee or migrant populations, where power asymmetries and institutional mistrust persist.

The HRA and NHS RECs recommend cultural mediation and the use of validated translated materials. However, failure to adequately assess comprehension or voluntariness in these contexts has led to ethics committee rejections and, in rare cases, withdrawal of research approval.

Patients lacking capacity: oncological and geriatric examples

A particularly fraught area is represented by patients with cognitive decline, mental illness or neuro-oncological conditions. In such cases, capacity is often fluctuating, partial or questionable, and yet the therapeutic implications of participation may be profound.

In observational neuro-oncology studies, approximately one-quarter to one-third of patients with malignant glioma – including glioblastoma multiforme – have been found to lack full decision-making capacity at the time of consent. A UK perspective study reported incapacity in 25% of patients with intracranial tumours, rising to 38% among those with World Health Organization grade IV disease, while other cohorts confirmed that around one-third of glioblastoma patients show compromised consent capacity.^30–32 The inconsistency arose from a lack of cognitive screening at the point of enrolment and overreliance on written documentation.

Legal repercussions in similar scenarios include:

invalidation of consent, exposing the study to claims of unlawful inclusion;

breach of duty of care, especially if the participant experienced harm;

potential for disciplinary proceedings by the GMC in cases where the breach is systemic or negligent.

The GMC's Good Medical Practice (2024 update) now requires explicit documentation of capacity assessment in all research settings involving vulnerable participants.³³

Implications

When the IC process is inadequately conducted or documented, the consequences are not merely academic. Competent authorities such as the MHRA, HRA and GMC may initiate:

study suspension or termination^20,34;

fines or sanctions against the sponsor or principal investigator^27,34;

fitness to practise hearings, which can result in professional censure.³³

IC in global contexts

As clinical research increasingly crosses national boundaries, the IC process faces considerable ethical, legal and cultural challenges. While international ethical standards such as the Declaration of Helsinki and CIOMS Guidelines^1,2 advocate for universal principles – autonomy, voluntariness, comprehension – their implementation varies substantially across jurisdictions. In the UK- or EU-based legal frameworks, these divergences pose not only operational difficulties but also significant medico-legal risks.

To clarify the operational interplay between statutory, regulatory and jurisprudential sources governing IC, Table 1 summarises the main legal instruments applicable to UK- and EU-based research practices.

Table 1.

Legal instruments governing IC in clinical research under UK and EU jurisdictions.

Legal source/instrument	Implications for consent validity
Mental Capacity Act 2005 ³	Defines capacity and procedures for enrolling incapacitated subjects in research
UK GDPR (as incorporated by the Data Protection Act 2018 and subsequent amendments) (ICO 2023) ⁶	Requires that consent to the processing of health-related data be explicit, specific, informed, freely given and revocable, in line with Articles 6, 7 and 9 of the GDPR, which remains in force and is applied under UK Law, with supervision exercised by the Information Commissioner's Office
Regulation (EU) 2016/679 (EU GDPR), Articles 6, 7, 9 ⁵	Requires explicit, informed, freely given and revocable consent as a lawful basis for processing health-related data within the EU
Human Tissue Act 2004 (section 2) ⁴	Consent must be appropriate and contemporaneous for use of human material
Montgomery v Lanarkshire Health Board [2015] ¹¹	Establishes the ‘material risk’ standard tailored to the participant
Re T (1992) ¹⁵	Consent is invalidated by undue influence from third parties
Declaration of Helsinki (2024 revision) ¹	Stipulates re-consenting when new information arises and mandates that the welfare of the research participant takes precedence over the interests of science and society
Medicines for Human Use (Clinical Trials) Regulations 2004 as amended³⁴	Permits deferred consent in emergencies under strict statutory conditions, with subsequent re-consent required when capacity is re-gained
MHRA Inspection Reports (2022)²⁷	Frequent findings include lack of documentation of re-consent and improper consent tracking

IC: informed consent; EU: European Union; GDPR: General Data Protection Regulation; MHRA: Medicines and Healthcare products Regulatory Agency.

Legal pluralism and ethical relativism

Legal and ethical standards around IC diverge markedly between common law systems and jurisdictions shaped by customary, religious or collectivist traditions.

For example, in parts of sub-Saharan Africa or South and Southeast Asia, collective decision-making through family or community leaders remains normative. In such settings, obtaining direct, individualised consent may be perceived as intrusive or disrespectful, and verbal or non-verbal assent may carry culturally significant weight.⁸

Transnational research and the risk of ‘ethics dumping’

The phenomenon of ‘ethics dumping’ – where ethically contentious research is re-located to countries with weaker regulatory oversight – has received growing scrutiny from both scholars and competent authorities.³⁵

IC is often at the centre of such practices. Studies have documented the use of translated but legally ambiguous consent forms, absence of formal ethics review by local committees and reliance on verbal or community consent that would be unacceptable under UK HRA or GDPR standards.

In response, the European Commission, through the Horizon 2020^36,37 programme and subsequent initiatives, has mandated due diligence procedures to prevent the outsourcing of ethically problematic research to low-oversight environments.³⁸

Case example: community consent versus legal autonomy

A case study often cited involves research conducted in a rural district of Kenya, where investigators obtained Authority's approval and community-level assent but failed to ensure individual-level understanding and freedom to decline. Although the research protocol passed local REC review, subsequent evaluation by an EU-based audit team found the process incompatible with GDPR consent standards (i.e. unambiguous, informed, specific, freely given).²⁸

Similar concerns have arisen in UK-based collaborative studies conducted in refugee camps or among displaced populations, where language, trauma and dependence on healthcare provision create environments of structural vulnerability that compromise voluntariness.^35,28

Regulatory and ethical recommendations

For research institutions subject to UK or EU jurisdiction, compliance with home standards cannot be suspended when operating abroad. This means:

Ensuring that local RECs or IRBs apply equivalent scrutiny as UK counterparts.

Involving community representatives in consent design without bypassing individual consent.

Using linguistically and culturally validated materials and documenting all consent procedures, even where oral assent is contextually appropriate.

Maintaining full transparency with sponsors, authorities and oversight bodies regarding consent methodology.

Failing to adhere to these standards may result not only in ethical breach, but also in non-compliance with UK research governance frameworks, potentially jeopardising publication, funding or legal standing.

Jurisdictional fragmentation and normative conflict

Different jurisdictions impose different legal standards on the IC process. The UK operates under a hybrid regime of common law duties (e.g. Montgomery¹¹), statutory provisions such as the Mental Capacity Act 2005³ and Human Tissue Act 2004,⁴ and guidance from bodies like the HRA²⁰ and GMC.²⁴

By contrast, the EU mandates IC through the GDPR for all health-related data processing, regardless of geographic location, if the data participants reside in the EU.⁵

The US Common Rule (45 CFR 46), while sharing ethical principles with the UK framework, differs procedurally: for instance, it permits broad consent for unspecified future use of data and bio-specimens – an approach that may conflict with GDPR's requirement of specificity and purpose limitation.³⁹

These divergences can create regulatory conflicts, especially in multi-national trials, where UK investigators are expected to comply simultaneously with home standards and local legal environments that may lack equivalent protections or enforcement mechanisms.

The need for regulatory harmonisation and legal clarity

Despite shared ethical principles, consent requirements remain inconsistently interpreted across UK, EU and other international frameworks.

This variability creates uncertainty for multi-national research sponsors, particularly when reconciling broad consent models with UK regulators’ expectations for specificity and transparency. Moreover, differences in consent validity thresholds – especially for secondary data use and bio-banking – pose challenges for collaborative initiatives.

A consistent regulatory framework would reduce legal risk, improve audit readiness and foster public trust.

Contractual and institutional due diligence

To mitigate legal exposure, UK-headquartered sponsors must ensure that appropriate due diligence is conducted prior to study initiation, including:

Verification that local ethical review bodies meet standards equivalent to those required by the UK Research Governance Framework.

Inclusion of explicit clauses in contracts and Material Transfer Agreements requiring that consent procedures adhere to UK standards.

Documentation of local regulatory approval, consent forms, translations and cultural adaptations, which may be subject to audit by the MHRA or funding bodies (e.g. UK Research and Innovation).⁴⁰

Failure to comply may result in suspension or termination of funding, withdrawal or suspension of an REC favourable opinion or legal or regulatory action. In one 2022 case, an NHS-affiliated genomics study was paused while the REC reconsidered its favourable opinion following concerns about consent materials and participant communications⁴¹; for studies conducted in non-EU countries, HRA and Information Commissioner's Office (ICO) guidance requires GDPR/UK GDPR-compliant transparency wording explicitly addressing international data transfers, and RECs may withhold or suspend approval until compliant.^42–44

Innovations and new approaches to IC

The IC process, traditionally centred on paper forms and verbal explanations, is increasingly shaped by technological innovation. In an effort to enhance comprehension, accessibility and documentation, investigators and institutions have explored a range of new tools, including electronic consent (e-consent) platforms, multi-media decision aids, interactive comprehension checks and even virtual or augmented reality modules.

Electronic consent (e-consent)

E-consent platforms enable participants to review study information, ask questions and provide consent digitally, often via web portals or tablets. In the UK, HRA Guidance on Electronic Consent (2020)⁴⁵ affirms that e-consent is permissible provided that:

the process supports informed decision-making;

there is a verifiable audit trail;

the participant has the option to ask questions in real time.

Under GDPR Article 7, electronic consent must be demonstrably specific, unambiguous, informed and participants must retain the right to withdraw as easily as they gave consent.⁵

Legal validity also requires that consent interfaces accommodate the needs of people with diminished capacity, in compliance with the Mental Capacity Act 2005, which emphasises accessible presentation and supported decision-making.³

Multi-media and interactive formats

A growing body of research suggests that multi-media tools – videos, infographics, narrated animations – can improve participant understanding, particularly in populations with low literacy or cognitive impairment.⁴⁶ Some platforms now integrate adaptive comprehension checks that require the participant to correctly answer key questions before proceeding to consent.

However, evidence from UK-based randomised studies indicates that while these tools improve recall and perceived understanding, they do not always lead to better decisional quality, especially when used without human interaction.⁴⁷

Moreover, there are legal uncertainties regarding data security, identity verification and auditability of interactive interfaces, particularly where participants are geographically remote or using personal devices with inadequate cybersecurity safeguards.

Innovations in vulnerable populations: risks of exclusion and misuse

While innovation may enhance inclusivity, it may also unintentionally exacerbate digital inequalities. Populations such as the elderly, socio-economically disadvantaged, migrants or individuals with cognitive impairments may lack access to the technology or skills needed to engage with advanced consent platforms.

The GMC's guidance on research involving vulnerable adults (2024) stresses that consent processes must not discriminate by design, and that digital tools must be tested for usability and accessibility before implementation.³³

Ongoing and dynamic consent

Beyond technology, conceptual innovations such as ‘dynamic consent’ – a digitally mediated model that enables participants to give, modify or withdraw consent in real time – or ‘ongoing consent’ – the regular re-affirmation of participation throughout the study – seek to re-conceptualise consent as a longitudinal dialogue rather than a one-time act.^48,49 These models enable participants to:

modify or withdraw consent at any time;

choose how their data is used in future research;

receive updates about study results and protocol changes.

These models align with GDPR's principles of data minimisation, purpose limitation and withdrawal rights, but require robust infrastructure, governance and funding.

The shift from traditional, static consent models to ongoing and dynamic frameworks presents not only ethical advantages but significant legal and operational implications. Table 2 outlines key differences between standard and dynamic consent systems in terms of validity, participant engagement and medico-legal defensibility.

Table 2.

Comparison between standard and dynamic consent models in clinical research.

FEATURE	STANDARD CONSENT	ONGOING/DYNAMIC CONSENT
LEGAL VALIDITY (INITIAL)	Based on single act of informed agreement; validity tied to documentation	Requires infrastructure to ensure sustained legality over time
PARTICIPANT AUTONOMY	Limited to initial decision; no iterative input	Participants can revise choices, preferences or withdraw consent at any point
DATA USE CONTROL	Often broad or blanket; future uses may not be re-consented	Specific, granular consent for data re-use, secondary studies or bio-banking
OPERATIONAL COMPLEXITY	Simple to implement; minimal informatic needs	Requires digital interface, tracking systems and secure data architecture
ETHICAL ROBUSTNESS	Risks formalism; may fail to ensure true comprehension or contextual fit	Enhances respect for autonomy and transparency through active, continuous involvement
FORENSIC DEFENSIBILITY	Easier to challenge in court if context changes are not reflected	Stronger evidentiary support if dynamic logs and real-time participant choices are tracked

These conceptual differences have tangible procedural consequences, as illustrated in Figure 1, which compares the operational flow of standard and ongoing consent models.

Figure 1.

Operational flow of standard versus ongoing consent models. This diagram illustrates the linear process of traditional consent compared to the adaptive and interactive nature of ongoing consent systems. The latter incorporates participant re-engagement and updated disclosures, offering enhanced legal defensibility and ethical responsiveness.

As shown in Table 2, while dynamic consent frameworks demand greater infrastructural investment and governance, they offer increased forensic defensibility and participant-centred ethical robustness, aligning more closely with contemporary standards under GDPR and the Montgomery judgment.^5,11

This flowchart contrasts the linear structure of standard consent with the adaptive, feedback-oriented design of ongoing consent. While the standard model assumes consent remains valid throughout, the ongoing model incorporates updated disclosures and participant re-confirmation, offering stronger medico-legal safeguards.

Medico-legal risk and forensic relevance

Many of the legal instruments outlined in Table 1 have been central to forensic evaluations in real-world litigation concerning research consent procedures.

The medico-legal consequences of invalid or deficient IC extend well beyond regulatory non-compliance; they may constitute grounds for civil litigation – for example, in claims for negligence under Montgomery v Lanarkshire Health Board judgment; professional misconduct, with the GMC empowered to investigate cases of failure to obtain consent under Good Medical Practice (2024); and, in rare cases, criminal liability, where non-consensual intervention may amount to ill treatment under English common law.^9,11,33

Forensic medicine plays a pivotal role in this landscape. Medical experts are frequently appointed as court-appointed expert witnesses (Part 35 Civil Procedure Rules⁵⁰ in civil disputes involving research-related injuries or procedural irregularities.

Key areas of forensic concern include:

failure to obtain re-consent following a protocol amendment or re-gained capacity in emergency research;

improper use or secondary use of biological samples without renewed or specific consent;

documentation inconsistencies, including missing timestamps, witness signatures or translation records.

The forensic implications of these procedural lapses can be conceptualised through a cascading model of medico-legal escalation, presented in Figure 2.

Figure 2.

The forensic consent failure cascade. This schematic outlines the progression from procedural deficiencies in IC to regulatory, professional and legal consequences. It highlights the interplay between operational vulnerabilities, forensic indicators and institutional oversight in the context of UK and EU legal frameworks. IC: informed consent; EU: European Union.

As shown in Figure 2, forensic escalation often results from initial oversights – such as inadequate documentation or failure to re-consent (i.e. renewed consent from the same participant after a protocol amendment, material new information or re-gained capacity) – that become compounded by systemic vulnerabilities. Awareness of this cascade can help institutions anticipate legal scrutiny and implement safeguards accordingly.

These medico-legal issues have prompted a growing body of scholarship. Dove underscores the forensic implications of consent procedures in research settings, noting that ‘deficiencies in consent are increasingly scrutinised as potential indicators of systemic negligence, particularly when linked to institutional oversights’.⁵¹ Wale and Dewhurst similarly document a rise in expert assessments related to IC disputes, highlighting their role in litigation and ethics board enquiries.⁵²

Indeed, reports of invalid consent leading to litigation or retraction of research findings are no longer anecdotal. Well-documented precedents illustrate the medico-legal consequences of failing to obtain re-consent after substantial protocol amendments. The Havasupai litigation, for example, arose when bio-specimens were used for genetic studies beyond the scope of the original consent, culminating in legal settlement and institutional sanction, and it is now widely cited as a cautionary precedent in the governance of clinical research.⁵³ This case demonstrates that lapses in re-consent are not merely procedural shortcomings but may crystallise into enforceable legal claims and institutional liability, with direct implications for the design and oversight of contemporary clinical trials.

Another forensic analysis by Patel and Rowe explored the medico-legal ramifications of retrospective consent in bio-bank research, stressing that even minimal risks must be disclosed in a manner legally defensible in court.⁵⁴

Given these experiences, it is imperative that research institutions integrate forensic awareness – that is, the anticipation of how consent processes may later be scrutinised in litigation or disciplinary proceedings – into their consent protocols, ensuring documentation and practices are evidentially robust.^51,52 This includes not only ethical training, but legal literacy among principal investigators and collaboration with medico-legal advisors to ensure that consent processes are both operationally sound and evidentially robust in the event of judicial scrutiny.

Institutional sustainability and capacity building

As consent models evolve, research institutions must ensure their policies, staff and infrastructure are capable of maintaining ethically and legally sound practices. This includes:

training research staff on capacity assessment and culturally sensitive consent;

investing in compliant e-consent platforms with adequate cybersecurity and audit functionality;

integrating consent tracking into research data management systems.

Such measures are not only ethical imperatives but serve as risk minimisation strategies, particularly in an era of increasing regulatory scrutiny and public concern over data use and transparency.

Recommendations for policy and practice

In light of the above, several policy-level actions are recommended:

Develop binding, unified guidance integrating ethical, clinical and data protection principles applicable across UK and international contexts.

Mandate consent usability testing, especially for digital or vulnerable populations.

Ensure funding mechanisms accommodate the administrative burden of dynamic consent models.

Create national consent templates, harmonised with GDPR and legal case law, for common study types.

Such steps would enhance legal robustness, public trust and international alignment, thereby reinforcing the integrity of clinical research governance in the UK and beyond.

Conclusion

The process of obtaining IC in clinical research is not merely a procedural obligation but a juridical and ethical cornerstone of lawful and legitimate scientific enquiry. IC is best understood as a dynamic construct – legally codified, ethically grounded and operationally vulnerable.

Across diverse research contexts, the principle of IC is routinely challenged by constraints of capacity, culture, comprehension and coercion. These challenges are not abstract: failures in consent procurement have led to regulatory sanctions, reputational damage and legal liability, both in the UK and internationally.

To meet these risks, research institutions and competent authorities must ensure that consent frameworks are not only ethically sound but legally robust.

Ultimately, IC must be recognised not as a formality to be fulfilled, but as a mechanism of legal accountability – indispensable to the scientific credibility, legal defensibility and ethical legitimacy of modern research.

Footnotes

ORCID iDs

Deborah Bonifacio

Rosaria La Licata

Giovanni Tarditi

Giovanni Romeo

Diego Romeo

Guido Attilio Condorelli

Ethical considerations

This article does not contain any studies with human or animal participants.

Consent to participate

There were no human participants in this study, and consent from participants was not required.

Author contributions

Guido Attilio Condorelli: conceived and designed the review, led the legal and regulatory analysis and drafted major sections of the manuscript.

Deborah Bonifacio: performed systematic literature and regulatory search, synthesised evidence, drafted and edited several manuscript sections and handled formatting and submission processes.

Rosaria La Licata and Giovanni Tarditi: contributed to the medico-legal and clinical interpretation, critically revised the manuscript for important intellectual content and approved the final version.

Giovanni Romeo and Diego Romeo: contributed to conceptual integration of forensic aspects, reviewed the manuscript and approved the final version.

All Authors have read and approved the final submitted version and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.

Declaration of conflicting interests

Deborah Bonifacio, Giovanni Romeo and Diego Romeo are affiliated with Pharmaceutical Management Company (PMC) Ltd, a private firm operating in the pharmaceutical field. The present manuscript was not commissioned, funded or influenced by PMC or any of its clients. The other authors declare no other competing interests.

Guarantor

Guido Attilio Condorelli acts as the guarantor for this work. He accepts full responsibility for the integrity of the content, has full access to all sources and materials used in the preparation of the review and controlled the decision to submit the manuscript for publication.

Notes

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