Ethics and Privacy in Intensive Care Research

Dr Ian Seppelt

Dept of Intensive Care Medicine

Nepean Hospital, Sydney

Ethics or ‘research ethics’?

1. Beneficence

2. Non-maleficence

3. Autonomy

4. JusticeDistributive justice

Lots of paperwork?

1. National Statement

2. Declaration of Helsinki

3. ICH Good Clinical Practice

4. NSW Privacy Act

5. NSW Human Tissue Act

6. NSW Guardianship Act

Dealing With Ethics Committees!

Know your enemy

In 2003 there were 226 Human Research Ethics Committees

51 (23%) in NSWThey approved 18,323 projectsThey rejected 232

www.nhmrc.gov.au/issues/pdf/hrecarp.pdf

Know the rules and give them what they expect!

X friend

National Statement on Ethical Conduct in Research Involving

Humans

1998; draft revision Dec 2004

http://www.nhmrc.gov.au/publications/pdf/e35.pdf

1. Principles of Ethical Conduct

1.1 Respect for human beings, justice, research merit and integrity, and beneficence

Research merit and integrityJustice in researchBalancing benefits and risks in researchRespect for human beings

1. Principles of Ethical Conduct

1.2 Consent to participation in researchGeneral requirements for consentConsent to future use of data and tissue in researchRefusing and withdrawing consentQualification of consent requirements

3. Ethical considerations specific to participants

3.4 Ethical considerations specific to research in people highly dependent on medical care

Research merit and integrity

3.4.1 “Research ….. is justified where it is likely that the research will lead to improvement of those interventions and will not pose a risk to participants greater than that inherent in their condition and present treatment”

Justice

3.4.2 “Because of their exposure to severe threats to their lives, the participation of people highly dependent on medical care may be essential to research that aims to improve interventions in those circumstances”

Balancing benefits and risks

3.4.5 “The distinguishing features of intensive care research are the difficulty in communicating with patients …. Wherever possible, consent to intensive care research, based on adequate information, should be sought from or on behalf of potential participants before admission to that research ”

Balancing benefits and risks

3.4.8 “The distinguishing feature of research involving unconscious people is that …. it is impossible for them to be informed about the research or determine their wishes ….”

Balancing benefits and risks

3.4.8 “The distinguishing feature of research involving unconscious people is that …. it is impossible for them to be informed about the research or determine their wishes …. Anyone who is unconscious should normally be included only in minimally invasive observational research or research designed to investigate improvements to the treatment of that individual’s condition”

Respect for human beings

3.4.9 “When … conformity to the general principles of consent … is not feasible, and neither the individual nor the individuals’ representative can consider the proposal and give consent in advance, an HREC may approve a research project without prior consent if …

Respect for human beings

3.4.9 “When … conformity to the general principles of consent … is not feasible, and neither the individual nor the individuals’ representative can consider the proposal and give consent in advance, an HREC may approve a research project without prior consent if(a) the research is based on valid scientific hypothese which support a reasonable possibility of benefit over standard care,

(b) inclusion … is not contrary to the interests of the patient and does not impose an unfair burden of participation …

Respect for human beings

3.4.9 “When … conformity to the general principles of consent … is not feasible, and neither the individual nor the individuals’ representative can consider the proposal and give consent in advance, an HREC may approve a research project without prior consent if(c) the research is intended to be therapeutic for that patient and the research intervention poses no more of a risk than that which inherent in the patient’s condition …(d) as soon as reasonably possible the patient and/or relatives … will be informed of the patient’s inclusion in the research and of the option to withdraw from the research without any reduction in the quality of care.

18th World Medical Assembly ‘Declaration of Helsinki’ (1948, revised 1996)

Clinical research should

Be conducted by scientifically qualified personnelConform to generally accepted scientific principalsHave formally approved protocolsHave a balance between the research objectives and patient riskEnsure subjects their confidentiality and integrity

18th World Medical Assembly ‘Declaration of Helsinki’ (1948, revised 1996)

Clinical research should

Only be performed if subjects have received comprehensive study information and the subjects freely give consentCease if the hazards outweigh the potential benefitsEnsure the subjects can abstain from or withdraw participation at any timePublish accurate results

International Conference on Harmonisation ‘Good Clinical Practice’ 1997

“International ethical and scientific quality standard for designing, conducting,

recording and reporting trials that involve the participation of human subjects”

International Conference on Harmonisation ‘Good Clinical Practice’ 1997

Three tenets of GCP:

1. Patient protection (ethics)

2. Credible data (science), and

3. Control

When does QA in healthcare require independent ethical review?

NHMRC 2003

Nine questions….. If the answer to every question is ‘no’ then ethical review is not required

When does QA in healthcare require independent ethical review?

1. Is the consent from participants inadequate, or is the activity inconsistent with National Privacy Principle 2.1(a)

2. Does the QA pose any risks for patients beyond those of their routine care?

3. Does the QA impose a burden on patients beyond that experienced in their routine care?

When does QA in healthcare require independent ethical review?

4. Is the QA to be conducted by a person who does not normally have access to the patient’s records?

5. Does the proposed QA risk breaching the confidentiality of any individual’s personal information, beyond that experience in routine care?

6. Does the QA involve any significant departure from the routine clinical care provided to patients?

When does QA in healthcare require independent ethical review?

7. Does the QA involve randomisation or the use of a control group or a placebo?

8. Does the QA seek to gather information about the patient beyond that collected in routine clinical care?

9. Does the QA potentially infringe the rights, privacy or professional reputation of carers, health care providers or institutions?

When does QA in healthcare require independent ethical review?

Are you planning to publish your results?

Other complicating factors …

1. NSW Health Records and Information Privacy Act 2002

2. NSW Human Tissue Act, amended 2002

3. NSW Guardianship Act 1987 amended 1998

Health Records and Privacy Act 2002

15 Health Privacy Principles set out in Act …

1. Does this project involve the collection, use, or disclosure of personal health information which is identified, or from which the identity of the person can be reasonably ascertained?

2. Could the purpose of this project be served by collecting, using or disclosing de-identified information?

Health Records and Privacy Act 2002

3. Why can’t the purpose of the project be achieved using de-identified information?

4. Are you proposing to collect, use or disclose the health information with the consent of the individual(s) concerned?

5. From which organisations/bodies are you collecting personal health information?

…..

Health Records and Privacy Act 2002

10. Why is it impracticable to obtain the consent of the individual to collect, use or disclose their health information?

11. Please provide reasons why the collection, use or disclosure of this information is in the public interest, and why the public interest in the project substantially outweighs the public interest in the protection of privacy.

Human Tissue Act 2002

Human tissue, including blood, cannot be used for research without a priori consent from the patient

Person responsible cannot consentUnless the tissue was collected for usual clinical purposesOr unless the patient is under an order under the Guardianship Act

Guardianship Act 1987Section 5 Division 4A Clinical Trials

Allows proxy consent by person responsilbe for participation in a trial in which the individual cannot consentTrial must first be approved by local HRECBroad definition of clinical trial

Interested in new and experimental treatmentsNot phase 1 and 2 trials

Guardianship Act 1987Section 5 Division 4A Clinical Trials45AA The Tribunal may give approval only if it

is satisfied that

(a) the drugs or techniques are intended to cure a particular condition from which the patients suffer

(b) the trial will not involve any substantial risk (or .. not material risk greater than the risks associated with treatment)

Guardianship Act 1987Section 5 Division 4A Clinical Trials45AA The Tribunal may give approval only if it

is satisfied that

(c) the development of drugs or techniques has reached a stage at which … it is appropriate they be available to patients who suffer from that condition even if not able to consent

(d) it is in the best interests of patients … that they take part in the trial

Guardianship Act 1987Hierarchy of Persons Responsible

1. A guardian (including an enduring guardian)2. The most recent spouse or de facto spouse

with whom the person has a close, continuing relationship,

3. An unpaid carer who is now providing support to the person or provided this support before the person entered residential care

4. A relative or friend who has a close personal relationship with the person

Conducting Quality Research in Intensive Care

Conducting Quality Research in Intensive Care

1. Formulate a questionLiterature review, prior negative studiesStudies in progress (Cochrane database)

2. ‘So what?’Will the results be meaningful?

3. Is the intervention SAFE?Preclinical and pilot studiesPhase I and II studies using SAME methodology before progressing to a phase III study

Conducting Quality Research in Intensive Care

4. Is the study adequately powered?An underpowered study is worthlessPilot study to get data for accurate sample size calculation

5. How will consent be handled?Prospective consent by patient?Proxy consent by family or ‘person responsible’?Retrospective or no consent in resuscitation studies

Conducting Quality Research in Intensive Care

6. How will patients be randomised?How will treatment allocations be concealed?Have sources of bias been minimised?

7. How will the study run logistically?Is the protocol idiot proof?Does the entire ICU staff understand the study?Conflicts of eligibility

Conducting Quality Research in Intensive Care

8. What are the study outcomes?Primary outcome should be unambiguous, easily measured and clinically importantSurrogate end points must be validated

9. How will the data be captured?Data de-identifiedCase record form should be comprehensive without being onerous

Conducting Quality Research in Intensive Care

10. How will the data be analysed?Are the statistics validConsult a statistician!

11. How will the results be published or communicated?

Negative studies are just as valuable as positive onesAvoid ‘publication bias’

Good luck!