24-10-22 – Research Ethics

Question 1

Learning outcomes

Answer 1

• Outline the key arguments often cited for/against the use of animals in research
• Explain the three principles governing the use of animals in research (from the Home Office policy)
• Outline the regulatory role of the Home Office in animal research, and the National Research Ethics Service (NRES) & local ethics committees in human research
• Recognise the importance of the Declaration of Helsinki (2013) in human research
• Identify the different ethical issues raised by the Tuskegee Syphilis trial, the Guatemalan STD trial, and the case of Henrietta Lacks
• Debate the need for transparency in publication authorship and declaration of conflicts of interest
• Explain why informed consent is important in research and some of the difficulties that can arise in the process

Question 2

What 3 parts of research ethics are involved for both animal and human research?

What other 2 things are also regulated?

Answer 2

• 3 parts of research ethics that are involved for both animal and human research:
  1) Laws
  2) Guidance
  3) Committees
• Human gametes and embryos are also regulated

Question 3

What are 9 points in the summary of the Nuremberg Code (1947)?

Answer 3

• 9 points in the summary of the Nuremberg Code (1947):

Question 4

What are 8 major historical events affecting the current status of ethical clinical research?

Answer 4

• 8 major historical events affecting the current status of ethical clinical research

Question 5

When was the original version of the Declaration of Helsinki?

When was the latest version?

Why did the WMA develop the Declaration of Helsinki?

What 5 things does it cover?

Answer 5

• The original version of the Declaration of Helsinki is from 1964
• The latest version is from 2013
• The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data
• The Declaration of Helsinki covers:
  1) Consent (also be aware of coercion)
  2) Confidentiality (including resulting data)
  3) Risks and burdens
  4) Post-trial provision
  5) Publication

Question 6

What 3 things are considered human research?

What ethical body regulates research ethics involving the NHS?

What about at local level?

What ethical body regulates ethical research outside of the NHS?

Answer 6

• 3 things that are considered human research:
  1) Participants
  2) Data
  3) Tissue
• If involving NHS staff, patients or premises: National Research Ethics Service (NRES)
• Local level NHS: NHS Research Ethics Committee (NREC)
• If not involving NHS, then Local level: Research Ethics Committee (REC) E.g. here at St Andrews, UTREC

Question 7

What are the 4 criteria for informed consent?

Where is informed consent in the Nuremberg Code and Declaration of Helsinki?

Answer 7

• 4 criteria for informed consent:
  1) Patient must have capacity
  2) Patient must give consent voluntarily
  3) Patient must be informed
  4) Consent must be continuing
• Informed consent is the First Principle of the Nuremberg Code
• Several articles address this in Declaration of Helsinki

Question 8

What is said about informed consent in the Declaration of Helsinki?

Where is it mentioned?

Answer 8

• Informed consent in the Declaration of Helsinki
• Mentioned in articles 25-32 of Declaration of Helsinki 2013

Question 9

What 7 things should we be alert to concerning informed consent?

Answer 9

• 7 things we should be alert to concerning informed consent:
  1) Participant feeling pressure into agreeing
  2) The problem of incentives
  3) Sufficient information
  4) Vulnerable patients (see work of Carl Elliott)
  5) Importance of coding & anonymisation of results (respect for autonomy) –
  6) Distinction between therapeutic & non-therapeutic research
  7) Differences in ethical frameworks in different populations (80% of approved drugs in US used data from clinical trials in other countries)

Question 10

What occurred in Tuskegee Syphilis Trials?

Answer 10

• Tuskegee Syphilis Trials:
• Aka “Tuskegee Study of Untreated Syphilis in the Negro Male” (1932)
• “a study to record the natural history of syphilis in hopes of justifying treatment programs for blacks.”
• US Public Health Service (President Clinton apologised 1997)
• 600 African-American men: 399 with syphilis, 201 without
• No informed consent: participants told they were being treated for “bad blood” (not given diagnosis, nor effective treatment)
• Meant to last 6 months, instead lasted 40 years
• Incentives: free medical exams, free meals, and burial insurance
• Examined regularly but not treated for the disease, even after penicillin became drug of choice in 1947 (* note: nor were they allowed to be treated in clinics/hospitals in area)
• 1974: $10 million out-of-court settlement was reached for participants and their families

Question 11

What occurred during the Guatemalan STD Trials

Answer 11

• Guatemalan STD Trials:
• Guatemalan experiments were uncovered in 2010 by Susan Mokotoff Reverby, took place in 1946-48
• President Barack Obama apologized to Guatemala, launched an investigation: “the Guatemala experiments involved unconscionable violations of ethics, even as judged against the researchers’ own understanding of the practices and requirements of medical ethics of the day”.
• US govt, with Guatemalan colleagues, experimented on 5000+ Guatemalan soldiers, prisoners, people with psychiatric disorders, orphans and prostitutes
• Justified as “results would have widespread benefits and help Guatemala to improve its public health service”
• No evidence that consent was sought (NB: cf US)
• Exposed 558 soldiers, 486 patients at psychiatric hospital, 219 prisoners, 6 prostitutes, and 39 others to gonorrhoea, syphilis or chancroid
• Measured accuracy of diagnostic tests on orphans, those with leprosy, people at psychiatric hospital, prison and army

Question 12

What occurred during the case of Henrietta Lacks?

Answer 12

• The case of Henrietta Lacks
• 1951: cells from Henrietta’s cervix are cultured in vitro, and become the first immortal human cell line HeLa
• 1951: Henrietta dies from cervical cancer
• HeLa cells are shipped all over the world, and used in all kinds of medical research
• But… Henrietta herself didn’t know this, nor did her family
• No knowledge shared or consent sought
• HeLa cells have made some people a lot of money, Lack’s family have struggled to access the healthcare they need
• Justification? Material was no longer “hers”, material would have been thrown away, for the common good

Question 13

What are problems that arise in publication ethics?

Answer 13

• Problems that arise in publication ethics:

1) Authorship – what counts as an author?

2) Conflicts of interest
* “Having a competing interest does not, in itself, imply wrongdoing. However, it constitutes a problem when competing interests could unduly influence (or be reasonably seen to do so) one’s responsibilities in the publication process” * E.g. financial ties, academic commitments, personal relationships, religious or political beliefs, institutional affiliations

3) The area of reproducibility (or lack thereof..)
* Looked at in reports:
* Reproducing results: how big is the problem? (THE, 3/9/15)
* How science goes wrong (The Economist, 19/10/13)
* Can be a big problem in psychology research, where there can be a reproducibility crisis, as it can be difficult to run the same tests and get the same results

Question 14

What 2 areas of research are animals used in?

Answer 14

• 2 areas of research are animals used in:
  1) Basic research – aimed at improving scientific knowledge/theories
  2) Applied research – application of theories for e.g. treatments, toxicity

Question 15

What does animal research help to do in the making of medicine?

Describe a flow chart of medicines being made

Answer 15

• In the making of medicine, animal research helps in ruling out nay medications that would be dangerous to be consumed by humans
• Flow chart of medicines being made

Question 16

What 7 aspects do we consider in animal research?

What does Peter Singer look into?

What did this lead to the formation of?

Answer 16

• 7 aspects we consider in animal research:
  1) Benefits
  2) Model – do we need a normal mouse or genetically modified one?
  3) Sentience – Certain animals more intelligent
  4) Value – mice cheaper than horses
  5) Moral agency – using amoeba instead of humans/monkeys
  6) Spiritual/religious potential
  7) Human achievement
• Peter Singer: seeking not equality of treatment, but equality of consideration of interests
• From that, Singer’s speciesism argument (Practical Ethics, 1979)

Question 17

What is mentioned in Singer’s speciesism argument (Practical Ethics, 1979)?

Answer 17

• Singer’s speciesism argument (Practical Ethics, 1979):
• To the hypothetical question about saving thousands of people through a single experiment on an animal, opponents of speciesism can reply with a hypothetical question of their own: would experimenters be prepared to perform their experiments on orphaned humans with severe and irreversible brain damage if that were the only way to save thousands? ( I say ‘orphaned’ in order to avoid the complication of the feelings of the human parents.) If experimenters are not prepared to use orphaned humans with severe and irreversible brain damage, their readiness to use nonhuman animals seems to discriminate on the basis of species alone, since apes, monkeys, dogs, cats and even mice and rats are more intelligent, more aware of what is happening to them, more sensitive to pain, and so on, than many brain-damaged humans barely surviving in hospital wards and other institutions. There seems to be no morally relevant characteristic that such humans have which nonhuman animals lack.
• Experimenters, then, show bias in favour of their own species whenever they carry out experiments on nonhuman animals for purposes that they would not think justified them in using human beings at an equal or lower level of sentience, awareness, sensitivity, and so on.
• If this bias were eliminated the number of experiments performed on animals would be greatly reduced.

Question 18

What 2 animal research regulation acts are in place in the UK?

What does the home office say in regards to animal testing?

What did this lead to the banning of?

Answer 18

• 2 animal research regulation acts are in place in the UK:
  1) The Cruelty to Animals Act, 1876 (1st country to do so)
  2) Animals (Scientific Procedures) Act 1986 (ASPA)
• The home office on animal testing:
• “in determining whether and on what basis to grant a project license the Secretary of State shall weigh the likely adverse effects on the animals concerned against the benefit likely to accrue as a result of the programme to be specified in the license”
• This lead no cosmetics, toiletries ingredients, tobacco or alcohol products being tested on animals since 1998

Question 19

What are the 3Rs in the ASPA?

Answer 19

• 3Rs in the ASPA (Originally from Russell & Burch in 1959):

1) Replacement
* e.g. alternative technologies (in vitro, biochemical, mathematical & computer models); use lower organisms instead of sentient ones

2) Reduction
* e.g. better study design to allow use of fewer animals; better storage of data

3) Refinement
* e.g. improve housing; minimise pain; improve welfare

Question 20

Who advises the home office?

How is eligible research reviewed and monitored?

What 3 different ways are licenses granted?

What is the concordat on openness?

Answer 20

• The Home Office is advised by Animal Procedures Inspectorate
• Each local arena - animal ethics committee (here in St Andrews, AWEC) – review & monitor all eligible research, using ASPA & Home Office guidelines, so this can be displayed to the home office about how their guidelines are being followed
• Licences are granted in 3 different ways:
  1) Site license e.g Uni of St Andrews
  2) Personal license – individual to each person
  3) Project license
• The Concordat on Openness is a set of commitments for UK-based life science organisations to enhance their animal research communications