Ethics in Human Research

Question 1

True or false? You would not need to get ethical approval to work with data from recently deceased NHS patients.

Answer 1

False. You need to get NHS approval to work with patients or users of the NHS, including relatives or carers, and the recently deceased.

Question 2

Would you need ethical approval to access data, organs, or other bodily material of past and present NHS patients?

Answer 2

Yes.

Question 3

You would need ethical approval to perform research involving foetal material and IVF involving NHS patients. True or false?

Answer 3

True.

Question 4

Would you need ethical approval if you wanted to carry out research that involved the use of/access to NHS premises or facilities?

Answer 4

Yes.

Question 5

You are looking to carry out research involving NHS staff, would you need to get ethical approval?

Answer 5

Yes.

Question 6

You are looking to carry out a trial of a drug or device on healthy volunteers in the NHS, would you need to get ethical approval?

Answer 6

Yes.

Question 7

List some cases for which you would need to get ethical approval for research within the NHS.

Answer 7

1) . Patients or users of the NHS including relatives, carers and recently deceased.
2) . Access to data, organs or other bodily material of past and present NHS patients.
3) . Foetal material and IVF involving NHS patients.
4) . The use/access to NHS premises or facilities.
5) . NHS staff.
6) . Healthy volunteers where a drug or device is being tested.

Question 8

There are a number of cases for which you would need to get ethical approval whether or not they take place within the NHS. List 7 such cases.

Answer 8

1) . Adults lacking capacity to consent for themselves.
2) . Exposure to ionising radiation.
3) . Human tissue.
4) . Investigational medical devices.
5) . Investigational medicinal products.
6) . Practising midwives.
7) . Processing confidential patient information without consent.

Question 9

When would healthy volunteers participating in research require ethical approval?

Answer 9

Healthy volunteers participating in drug or device trials require ethical approval under legislation.

It is strongly recommended that all research on healthy volunteers gains ethical approval.

Question 10

Which of the following require ethical approval?

1) . Research
2) . Clinical Audit
3) . Service Evaluation

Answer 10

Research requires ethical approval. Clinical audit and service evaluation does not require ethical approval.

Question 11

Describe the differences between audits, service evaluations and research.

Answer 11

Research derives new knowledge, addresses clearly defined questions and aims, usually involves collecting data and requires ethical approval.

Clinical audit assesses the level of service being provided. It measures against a standard. Clinical audit usually involves analysis of existing data but may include interviews and questionnaires. It does not require ethical approval.

Service evaluation judges current care. It measures current service without reference to a standard. It usually involves analysis of existing data but may include interviews and questionnaires. Service evaluation does not require ethical approval.

The line between research, clinical audit and service evaluation can become blurred. If in doubt you should seek advice as to whether you require ethical approval or not.

Question 12

You want to conduct research that has NHS involvement and legislative requirements. How do you gain ethical approval?

Answer 12

You must consult the National Research Ethics Committees (RECs) and the local NHS R and D approval body.

Question 13

True or false. Approval from the National Research Ethics Committees (RECs) is all you need if you want to conduct research that has NHS involvement and legislative requirements.

Answer 13

False. You need the RECs approval and Local NHS R and D approval.

Question 14

Who would you consult to gain approval to carry out audits and/or service evaluations?

Answer 14

The local NHS Audit office.

Question 15

Who would you consult to gain approval to carry out research with healthy volunteers?

Answer 15

The local ethics committee such as the University of Nottingham Ethics Committee.

Question 16

What is the NRES?

Answer 16

The NRES is the National Research Ethics Service

Question 17

What does the National Research Ethics Service (NRES) consist of?

Answer 17

The NRES consists of:

1) . NHS Research Ethics Committees (RECs)
2) . Volunteer Members and Chairs that sit on RECs
3) . REC coordinators and local managers

Question 18

What is the mission of the National Research Ethics Service (NRES)?

Answer 18

The mission of the NRES is:

1) . To protect the rights, safety, dignity and well-being of research participants
2) . To facilitate and promote ethical research of potential benefit to participants, science and society

Question 19

Describe the role of Research Ethics Committees (RECs).

Answer 19

The Research Ethics Committees review applications for research and give an opinion about the proposed participant involvement and whether the research is ethical.

The application includes protocol, consent form, patient information sheet and advertising material.

The RECs are entirely independent of research sponsors.

The RECs give an opinion after 35-60 days.

Question 20

For research projects that have NHS involvement and legislative requirements you are required to obtain approval from National Research Ethics Committees and Local NHS R and D approval. What must the NHS organisations ensure before granting R and D approval?

Answer 20

NHS organisations must ensure:

• There are adequate arrangements and resources,
• A sponsor has taken on responsibility for the study,
• The study has received ethical approval (where required),
• There is a clinical trial authorisation (where required),
• The allocation of responsibilities is agreed and documented,
• Appropriate contractual arrangements are in place,
• Legislations relating to the research is followed within the organisation,
• A person authorised to do so has given written permission on behalf of the NHS organisation

Question 21

What was the first act put in place to guide research on humans?

Answer 21

The 1906 Pure Food and Drug Act.

Question 22

What code first stated that ‘the voluntary consent of the human subject is absolutely essential’?

Answer 22

The Nuremberg Code 1948

Question 23

What amendments to ethical regulations did thalidomide lead to?

Answer 23

1950s Thalidomide led to Kefauver Amendments (1962) to the Food, Drug and Cosmetic Act: drug manufacturers required to prove effectiveness and greater drug safety

Question 24

In what year was the declaration if Helsinki from the World Medical Association?

Answer 24

1964

Question 25

What is the declaration of Helsinki?

Answer 25

The declaration of Helsinki was developed by the world medical association as a set of ethical principles for the medical community regarding human experimentation.

It was first developed in 1964 and has since been amended 6 times.

The declaration if Helsinki is the definitive document on medical research. 2008 is the current version. It contains 35 principles in a 5 page document.

Question 26

Describe the basic principles of the Helsinki Declaration.

Answer 26

1) . Respect for the individual, their right to self determination and the right to make informed decisions, both initially and during the course of research.
2) . The investigator’s duty is solely to the patient or volunteers, and while there is always a need for research, the subject’s welfare must always take precedence over the interests of science and society.
3) . Increased vulnerability of individuals and groups calls for special vigilance. When the research participant is incompetent, physically or mentally incapable of giving consent, or is a minor, then allowance should be considered for surrogate consent by an individual acting in the subject’s best interest. In which case their assent should still be obtained if at all possible.

Question 27

Describe the operational principles of the declaration of Helsinki.

Answer 27

1) . Research should be based on knowledge of the scientific background, assessment of the risks and benefits, have reasonable likelihood of benefit to the population studied and be conducted by suitably trained investigators using approved protocols, subject to independent ethical review.
2) . Studies should be discontinued if the available information indicates that the original considerations are no longer satisfied.
3) . Experimental investigations should always be compared against the best methods, but under certain circumstances a placebo or no treatment group may be utilised.
4) . The interests of the subject after the study is completed should be part of the overall ethical assessment, including assuring access to the best proven care.

Question 28

What do we mean by the term ‘Good Clinical Practice’?

Answer 28

GCP is ‘an international ethical and scientific quality standard for designing, conducting and reporting trials that involve the participation of human subject’.

Question 29

What is the purpose of compliance with the principles of Good Clinical Practice?

Answer 29

Compliance with Good Clinical Practice ensures that:

• the rights, safety and well-being of subjects are protected
• the trial is consistent with the principles of the Declaration of Helsinki
• clinical trial data is credible

Question 30

What is the EU directive 2001/20/EC?

Answer 30

The EU directive 2001/20/EC was enacted in the UK by the Medicine for Human Use (Clinical Trials) Regulations 2004.

The EU directive mandates GCP inspections for all member states.

It applies to all clinical trials involving medicinal products and includes non-commercial trials and phase 1 studies.

Question 31

What are the main roles and responsibilities of the researcher within a trial or piece of research?

Answer 31

The principle investigator has chief responsibility. Their main responsibility is:

1) . To protect life, health, privacy and dignity
2) . To ensure research is justified
3) . To ensure the design of the experimental protocol is rigorous
4) . To ensure the study is performed in accordance with the approved protocol
5) . To maintain complete, accurate and retrievable records
6) . To only enrol appropriate subjects
7) . To ensure the subjects are fully informed, that they volunteer and that they have given valid consent

Question 32

Define informed consent.

Answer 32

Informed consent is ‘a process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is documented by a means of a written, signed and dated informed consent form.’

Question 33

List the essential elements that Patient Information Sheets (PIS/PIL) should have.

Answer 33

• Q and A format
• Purpose of trial
• Treatments and probability for random allocation
• procedures, duration
• subject’s responsibilities
• risks and benefits
• confidentiality of records, anonymity if published
• investigators contact information
• must have approval (REC and NHS R and D)

Question 34

Describe how valid informed consent should be obtained.

Answer 34

Valid informed consent should be give at least 24 hours between PIS/PIL and obtaining consent.

Valid informed consent should be taken by an investigator or person designated by the investigator.

Consent form must be signed by the person who has conducted the informed consent discussion.

Question 35

Describe the consent process for children under 16.

Answer 35

Consent of parent or legal representative is required.

Consent must represent assumed consent of the child.

Information to child given according to capacity for understanding, by experienced staff.

Explicit wishes of child capable of forming opinion considered.

Question 36

How would you go about obtaining consent from an incapacitated adult?

Answer 36

They will have a legal representative. A personal legal representative is a guardian with the power to consent and is usually the adults nearest relative. A professional legal guardian is a doctor responsible for medical treatment or a person nominated by healthcare provider or trust.

If the adult is unable to read/write an impartial witness is required throughout the entire discussion.

Question 37

What does the term ‘equipoise’ mean with regards to medical research?

Answer 37

Equipoise is ‘a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in the trial.’

Question 38

Describe the key points of the Human Tissue Act (2004).

Answer 38

• regulates the removal, storage and use of human tissue. This is defined as material that has come from a human body and consists of, or includes, human cells.
• creates a new offence DNA ‘theft’. It is unlawful to have human tissue with the intention of its DNA being analysed, without the consent of the person from whom the tissue came.
• makes it lawful to take minimum steps to preserve the organs of a deceased person for use in transplantation while steps are taken to determine the wishes of the deceased, or, in the absence of their known wishes, obtaining consent from someone in qualifying relationship.

Question 39

List 5 offences under the HTA 2004.

Answer 39

1) . Removing, storing or using human tissue without appropriate consent.
2) . Storing or using human tissue donated for a scheduled purpose for another purpose.
3) . Trafficking in human tissue for transplantation purposes.
4) . Carrying out licensable activities without holding a license from the HTA.
5) . Having human tissue with the intention of its DNA being analysed without the consent of the person.

Question 40

What does research on humans include?

Answer 40

1) . Any direct involvement of patients or healthy volunteers (from interviews/surveys to drug trials)
2) . Use of clinical data for research
3) . Use of biological materials for research
4) . Use of material derived from human tissue (i.e. DNA, primary cell lines)