L7 Ethics of involving human participants in clinical research

what led to the realisation that there were no generally accepted guidelines for medical research

Nuremberg trials of 1947

list the 10 principles of the Nuremberg code

• voluntary consent

• research- for the good society

• based on previous knowledge to justify the experiment

• avoids unnecessary physical and mental suffering

• research avoided if suspected that death will occur

• risk needs to be mitigated against and proportionate

• adequate facilities

• conducted by qualified persons

• subjects can end experiments- withdraw

• scientist should not continue if trial is likely to result in injury

describe the Helsinki declaration

• guidance for doctors operating in a dual role as clinician and researcher

• this has been revised a number of times

• ICH-GCP is routed in the Declaration of Helsinki principles

define a human participant

• a living human being

• human beings who have recently died

• foetuses

• embryos

how can human participants be involved in research

• directly through their physical presence

• indirectly through stored human tissue/body fluids or use of human data or records

what is the cornerstone of ethical research 

informed consent

define informed consent

the act of providing information to a potential research participant to enable them to:

• gain a full understanding of what their involvement in a study means 

• understand the researcher’s responsibilites

so they can decide whether or whether not to take part in the study

what are the 4 steps of informed consent

• giving of information

• discussion, clarification and review of information

• obtaining written and/or verbal consent

• process consent (ongoing revalidation of consent)

describe informed consent for vulnerable adults with learning or communication difficulty

• temporary: unconsciousness/some mental illnesses

• permanent: genetic/inherited/clinical condition

describe the legal position of informed consent for vulnerable adults

• the mental capacity act 2007

• medicines for human use (clinical trials) regulations 2004

• common law

what are HeLa cells

the world’s first immortal human cells

• produce an entire generation every 24 hours continuously

how many HeLa cells have been grown in the last 7 decades

more than 50 million tonnes

• first space mission- what happens to cells in zero gravity

• helped with important advances in human medicine- polio vaccine, chemotherapy, cloning, gene mapping, in vitro fertilisation

• allowed experiments that would have been impossible with a living human

• contributed towards 5 Nobel prizes for medicine

what is the origin of HeLa cells

Henrietta Lacks -died 1951

• cervical adeno-carcinoma

• cancer cells taken from cervix months before she died

• 1971 medical notes were given to journalist

• family did not learn about her immortality until more than 20 years after her death

• billions were made commercially from HeLa cells - family given no benefit

What was the alder-hey organ retention scandal

• pathologist collected organs from very young children at post-mortem examination between 1988-1996

• in most cases, without asking the permission of parents

• 850 body parts collected (2000 pots)

• not clear how the samples were used

describe the human tissue act 2004

framework for the regulation of storage and use of human tissue from the living, and the removal, storage and use of tissue and organs from the deceased for specified purposes

define inducement

the provision of an incentive to entice a person to carry out an action

• care needs to be taken where offering any incentive is planned, and ethical approval is always needed

describe the Tuskegee Syphilis study

• US public health service between 1932 and 1972

• 600 low-income black males recruited

• offered free medical care, free meals and burial insurance in return from their participation

• at study entry 400 had syphilis an were monitored over 40 years

• none were treated for syphilis or told there was a vaccine

• prevented participants from accessing treatment

• victims died of syphilis and their partners and children contracted the disease too

describe confidentiality

a participant must have their confidentiality maintained unless they have specifically consented to their personal details being disclosed

what is the General data protection regulation (GDPR)

• governs protection and control of personal data

• anyone processing personal data must comply with the regulation

define personal data

information relating to an identified or identifiable individual

principles of GDPR

• lawfulness, fairness and transparency

• purpose limitation

• data minimisation

• accuracy

• storage limitation

• integrity and confidentiality

• the ‘accountability’ principle

what sort of data is, or may be, personal?

• identifiable data

• confidential information

• sensitive information

• coded data

• linked anonymised

• unlinked anonymised

• data that relates to an individual

not covered: truly anonymous data

what data is identifiable

almost everything- varying degrees of precision

• strong- NHS number, local patient ID, uncommon diagnosis, telephone number

• medium- post code, date of birth, ethnicity, religion

• weak- gender, hair colour

who does GDPR (general data protection regulation) apply to

• everyone processing personal data

• carefully considered in advance of a research study with processes in place at all stanges

• recognising you are handling personal data is critical to managing it within the law

• ICO now applies large fines to those not complying

Prior to the late 1960s, rules for registration of pharmaceuticals were much less restrictive than they are now

• not necessary to show that the drug worked against what you claimed it would do

• you could bring a drug to market if the theory was good enough that it may work

expertise in conducting and analysing animal experiments was not as good as it is now

standards were needed for the regulation of drugs that were going to be brought to the marker

what was the Thalidomide Scandal

• drug developed as a sleeping tablet

• drug of choice was given for morning sickness during the first trimester of pregnancy- 1950s and early 1960s

• resulted in tens of thousands of children being born with severe congenital abnormalities

• highlighted that there were insufficient safe guards in relation to the ways in which the efficacy and toxicity of drugs were accessed before they were put on the market

what was the medicines act of 1968

• merged previous medical regulation

• provides a broad legal standard on the manufacture and supply of medicines which related to general practice

• divides medicines into prescription only, pharmacy, general

• defined the necessity of clinical trials and scientific evidence to inform on the safety and efficacy of medication

• requirements to look at the effects of drugs or the possible toxicity of drugs in relation to females who are pregnant and the foetus and the future development of the child

describe the clinical trials legislation

• medicines for human use regulations 2004

• medicinces for human use amendment regulations in 2025- coming into force on April 28th 2026

What is the UK policy framework for health and social care research 2018

• designed to set principles of good practice across all areas of health and social care research in the UK

• applies to organisations and individuals that have responsibilities for health and social care research

• includes funders, sponsors, researchers and employers, research sites and care providers

what were some of the 19 principles involving UK policy for health and social care research 2018 

health and social care

• scientific and ethical conduct

• approval

• insurance and indemnity

• respect for privacy

interventional health and social care research

• justified intervention

• duty of care

what was Northwick Park, London 2006

• healthy male volunteers given experimental antibody drug TGN 1412

• used in rheumatoid arthritis theoretically

• first human trial managed by Parexel for TeGenero of Wurzburg in Germany

• all men got very sick and had a low lymphocyte and monocyte count which after 48 hours started to increase again

describe UK research ethics committees

• ensure dignity, safety, rights and wellbeing of individuals 

• essentially about reducing risk associated with research

• patient participants (UK research ethics committee), non-patient participants (university ethics committee)