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Tim Harris!Emergency Medicine and Pre-
hospital Care!
Consent, Ethics and Legislation in Research & Emergency Medicine
Tim Harris Barts Health & QMUL
CONSENT Issue for society Individual vs group rights Individuals responsibility to society Varies thro culture and society
Medicine Consent vital part of health care and research
Historical Context!
n Hippocratic Oath
n I SWEAR BY APOLLO, the physician,
TO RECKON him who taught me this Art equally dear to me as my parents, to share my substance with him and relieve his necessities if required; to look upon his offspring on the same footing as my own brothers, and to teach his Art if they shall wish to learn it, without fee or stipulation.
n No mention of consent!n Behavior up to social standing of profession !
n (no abortion, infanticide, suicide)!
!!Historical !! ! !!Context
! !!n Medieval!
n Church influence, Hippocratic tradition!n Beneficence approach (Henri de Modeville 1260 - 1325)!
n Social duty, all citizens have moral duty to participate !in research providing safeguards are in place!
n Enlightenment!n Gregory (1724 - 1773) Prof Medicine Edinburgh!
n Information to be shared with patients!n Freedom of choice essential for happiness!
n 1800s debate on ethics & pts preferences common in journals!
Legal Perspective!
n Slater vs Baker & Stapleton (1767)!n B & S were paid to remove bandages from healing fracture but
decided to re-break leg with new equipment to test it!!!!!n Slater won!
n Mohr vs Williams (1905 US)!n Surgery on left ear, consented for right!n Surgeons lost, request for opinion is not right to operate, pt able
to balance risk - benefit of intervention!n Schloendorff vs Society New York Hospitals (1914)!
n Plaintiff specified no operation but fibroid removed under GA!n Plaintiff won, landmark case in pts right to self determination!
Historical perspective - Clinical trials and Medical Experimentation!
n Little formalized research!
n Biomedical research common and often expected by patients!
n No formal regulation!
After the War!n Public outcry to medical experiments
without consent by Nazi / Imperial Japanese doctors!
n Conflict !n Morality of research!n Participants as means to an end!n Cultural expectation!
The Nuremberg Code (1947)!n 10 principals for human experimentation to be acceptable:!
n Consent - voluntary, pt must have capacity & understanding!n Experiment should yield benefit for society and results should not
be obtainable from other means!n Experiment should be based on sound knowledge !n Experiment conducted to avoid unnecessary suffering!n No experiment should be conducted where there is an a priori reason to
believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects
n The risk should not outweigh the potential benefit n Preparations should be made against even remote possibility of harm or
death n The experiment will be conducted by qualified persons to the highest skill n The subject has the right to withdraw n The experiment should be terminated if there is reason to believe it will
harm
Declaration of Geneva!n WMA, 1948!
n Oath (not law)!n ‘not to use my medical knowledge contrary to the
laws of humanity’!n ‘the health of my patient will be my first
consideration’!n ‘Absolute secrecy to all I know of my pt’!
Declaration Of Helsinki (1964)!n Developed by World Medical Association & based on above!n Formalized medical research:-!
n Requiring consent!n Research no longer routine in clinical practice; !n Dr could combine mx and research only if research justified by
therapeutic value to that pt!
Did This Make research Safe?!
n Tuskegee Syphilis patients - African men observed 1960 - 1973 rather than offered tmt - to learn the natural hx of syphilis!
n Thalidomide given to pregnant women with no knowledge or consent and awareness of teratogenicity in animal studies!
n AZT trials vertical transmission!n Trovan vs ceftriaxone in mennigitis, Nigeria, 2002!
! !So no wonder the public are worried - ethics needs legal teeth!!
Consent and Capacity UK !! !!
n Capacity is assumed in UK law!n Capacity assumes!
n Understand given information!n Believe information!n Balance risks and benefits of treatment!
n Incapacity!n Tempory, permanent, fluctuating!
When was consent not required?!
n Pt unconscious and requiring tmt!
n Testing for notifiable disease!
n Pt legally incapable of providing consent!n Child!n Mental disability!
!!
Historical Legal rulings for consent!
Re C test!pt in Broardmoor prison Hospital!
n Developed gangrene - surgical opinion to amputate!n Pt did not consent!n Capacity ruled on the following!
n Can pt understand information?!n Does pt believe information!n Can pt weigh risks and benefits!
n If satisfied pt has capacity or competence!
Proxy Consent!n Clarified by F vs West Berkshire Health Authority!
n Mother wished her 36 yr old daughter to be sterilised!n Decision that proxy consent not acceptable for adult
whether unconscious, handicapped or mentally ill!n In these situations the clinicians view of ‘best
interests for pt’ was deemed appropriate!n This decision had to be supported by body of similar
professionals!n This common law ruling changed by Mental
Capacity Act 2005!
Research ethics committees (REC)!
n Devised to ensure research performed in NHS complies with recognised ethical standards & to protect the rights, safety & dignity of participants!
n Provides researchers with a point of consultation!
n Investigator not judge and jury for ethical issues in study!
n Lay, nursing and medical members!
What does the REC consider?!
n Scientific merit !n Affect of research on participants health & distress!n Potential hazards & facilities to deal with them!n Qualifications of researchers!n Financial rewards to participants and researchers!n Mechanism of consent & level of information
provided!
Legislation - EU Clinical Trials Directive 2001/20/EC!
n Based on ICH E6 GCP but turns this to law across EU!n Aimed to protect participants in clinical trials involving
medicines!n Not data collection, new devices or procedures!
n Describes responsibilities of researcher, REC and provisions for pts without capacity!
n Covers !n Manufacture!n Recruitment!n Design !
n No mention of research in emergency situations!
Legislation - EU Clinical trials Directive 2001/20/EC (article 5)!
n Trial Dr not allowed to determine pts best interests and enter them to trial!
n Consent required to be !n Informed!n Written!n Prior to participating!n Voluntary!n Withdrawn at any time!
Legislation - EU Clinical trials Directive 2001/20/EC!
Prior to participation in a trial requirement for written consent from legal representative of any person unable to consent!
!In the first instance, close relative, aware of his/her wishes
and independent of the research !!Personal Legal Representative (PeLR).!
!If this is not possible before it is medically necessary to give
the intervention then someone nominated by the NHS Trust as a Professional Legal Representative (PrLR) will fulfils role.!
2006 Amendment!
!Allows unconscious pts in emergency
situations to be enrolled in clinical trials
without prior consent provided trial has REC
approval!
Legislation - Medicines for Human Use (clinical trials) Regulations 2004 - key
points!n GMP - Good Manufacturing Practice on preparation and
labelling of products!
n GCP - along international guidelines!n Clinical trial approval - MHRA approval prior to
starting, registered on European database!n Inspections - to assess compliance with GCP!n Surveillance - adverse events, SUSARs!n Set up COREC - standardizing ethical process!
Mental Capacity act 2005 - Background!
!
n Statutory framework to empower & protect those unable to make own decisions!
n Who makes decisions, which situations, how to make them!
n Passed 2005, effect from April 2007!n This overrides current UK common law (that no one can
consent for another)!n Mainly deals with long term issues eg Lasting power of
attorney !
MENTAL CAPACITY ACT 2005"FIVE KEY PRINCIPLES!
n Presumption of capacity!n Individuals should be supported so they can
make their own decisions!n Right to make unwise / eccentric decisions!n Anything done on people lacking capacity must
be in their best interests!n Least restrictive intervention!
LEGAL REQUIREMENTS OF CONSENT:!
For a consent to be legally valid, it must be:!n Made by a person with capacity!n Based upon adequate information!n Voluntary!!
GENERAL PRINCIPLES:!
n A right to consent/refuse consent /withdraw consent!
n Consent can be verbal!
n A signed consent form does not necessarily mean consent is valid!
!
Newer Legislation - Mental Capacity act 2005 - research!
n Assumptions!n No potential to answer (research) question in pts
with capacity!n Research must be connected to condition causing
incapacity!n Research has potential to benefit pt in proportion
to risk of research!n Low benefit -low risk!n High benefit - high risk!
TEST FOR CAPACITY!n Two stage test for capacity to make decision:!
!1. !Is there an impairment of, or disturbance in the
functioning of, the person’s mind or brain? !!!!The impairment or disturbance of the mind or brain may occur in a wide range of situations, for example, people who are affected by the symptoms of drugs or alcohol misuse, mental illness, dementia, learning disabilities or the long-term effects of brain damage!
!!!
If yes proceed to part 2!!
TEST FOR CAPACITY!
2. Is the impairment or disturbance sufficient that the person is unable to make that particular decision?!
!A person is unable to make a decision for themself if unable to:!n Understand the information!n Retain that information!n Use the information as part of the decision making process!n To communicate the decision by any means!!
!It is a decision specific test and no assumptions should be made because of a person’s age, appearance or behaviour!
Mental Capacity Act 2005 and Research!
n Research may involve person lacking capacity if:!n REC agrees research is safe & relates to
subjects condition & can’t be performed on those with capacity!
n Involves minimal risk & intrusion of human rights!
n Carers (not paid) / nominated persons must be consulted and be free to withdraw subject - if not avail then PrLR!
Current Consent Legislation!n Hierarchy of consent is guidance from COREC
not law!n Pt!n Spouse!n Sibling!n Children!n Cousin!n Friend!n PrLR!
When to invoke a PLR!n When pt does not have capacity!
n How do you judge capacity!n Don’t get caught up here!n Common sense!n Does the pt understand you!
n Yes or no!
n If doubt invoke PLR and then review pt later date!
So where are we now?!n Consent and capacity valued by patients and the RECs!n Researchers consider legislation onerous & research is
compromised!n Research vs. audit??!
n Efforts to improve!n REC & R&D use info supplied multiple times!n Research on NHS staff, surveys & service evaln do
not need formal ethical review!
What effect is the Legislation having on (Emergency) Research!
n CRASH-1 Trial - UK patients recruited using Waiver of Consent !
n UK recruited ~50% of first 1000 patients!
n CRASH-1 trial ended May 2004 !n UK law to implement EU
Directive 2001/20/EC in force 1st May 2004!
n Waiver of Consent no longer legal – Prior Consent needed !
n CRASH-2 trial started May 05!n Graph illustrates the impact on
UK recruitment !0
50
100
150
200
250
1 2 3 4 5 6 7 8 9 10 11
Month
Pat
ient
s R
ecru
ited
CRASH (UK)
CRASH-2 (UK)
What effect is the Legislation having on (Emergency) Research!
n Recruitment down!n Increased time to enter trial, receive tmt; CRASH
2 data!n Consent waiver - 1 hour!n PLR nrly - 2 hours!n Relatives providing consent assoc reduced
recruitment!n Over half relatives providing consent in recent
French study of stroke found the process unpleasant & stressful!
n BMJ 332 17 June 2006!
Emergency medical research is vital for the protection of patients
Road traffic accident: Each year over a million people are killed in road traffic collisions worldwide and some 10 million people are injured or disabled by these events Murray and Lopez (1996)
War & Violence: The number of violence related deaths in the world is unacceptably high. WHO - Injury Prevention 2001;7:104–111 -
Non-trauma: e.g Cardiac arrest and Strokes: Cardiovascular Disease will be the leading cause of death and disability worldwide by 2020 mainly because it will increase in low- and middle-income countries Murray and Lopez (1996)
Murray CJL, Lopez AD. Global health statistics: a compendium of incidence, prevalence and mortality estimates for over 200 conditions. In: Harvard School of Public Health, Boston: Harvard University Press, 1996
She has a right to Treatment and medical progress
Research is now an issue of human rights
Cases!
n 86 male!n Self inflicted gun shot to abdomen!n Stated he would accept analgesia but no
other care!n Conversant but competence questioned!n Living will to refuse all care if he
presented with terminal condition!n Questions!
n Why now?!
n Intially resuscitated!
n Extubated and asked if he wanted care to continue; he did!
n Most psychiatric patients who are treated against their will subsequently approve this action!
Case 2!
n 62 yr old women with severe disabling painful OA!
n To ED with significant OD ppt by decline in her medical condition !
n Advanced directive written by her and provided by husband expressed her wish for no life saving treatment but dated 5 years previously following her parents care on ICU and death!
Case 2!
n Advanced directive ignored by team as!n Advanced directive did not address OD!n No clear knowledge of her state of mind at
time she wrote directive!n She had an eminently treatable OD!n Adverse events from treating her were small !
n At follow up patient was grateful and accepted the teams choices but would rather her wishes had been respected!
Case 3!
n 26 year old women!n Lethal dose of ethylene glycol ingested as
suicidal gesture!n Several previous ED visits and had
accepted treatment but this time declined and provided advance directive!
n Alert and fully competent in ED!n PHx depression, self harm and PD !
Case 3!
n Clinicians sort second clinical opinion and legal advice!
n Patient deteriorated and died!n Inquest !
n Coroner noted that she had capacity and as such any attempt at treatment would have been unlawful and represented assault!
n Subsequent debate that capacity was seondary to right to treatment!
Thank you
Potential Problems?!
n New Legislation over-rides UK common law which states no one can consent for anyone else!n Is consent just a ritual or rubber stamp?!
n Legislation Mental Capacity Act worded for situations where incapacity is long standing & long term!
n Law unlikely to change, European Legislation is here to stay!
Trial registration!n ICMJE (2005) initiated policy requiring all trials to
be entered into registry prior to enrollment n 5 registies worldwide n Largest registry clinical trials.gov
n 13153 registered trials within 1 month of legsln n Register with any registry participating with WHO
ICTRP, 5 worldwide n Trial - any prospective human research to evaluate
health outcomes
Remember Declaration Helsinki?!
n Provision 6!n ‘ Even the best prophylactic, diagnostic,
and therapeutic methods must be continuously challenged through research for their effectiveness, efficiency, accessibility and quality’!
n Research is now an issue of human rights!
CAPACITY 16 & 17!
n By S8 of the Family Law Reform Act 1969, a 16 or 17-year old child is treated as an adult for consent issues!
n Their capacity is measured by the Mental Capacity Act 2005!
n A parent or court can overrule a 16 or 17-year old child’s refusal of consent!
!
CAPACITY – UNDER 16 !
How to decide whether child under 16 has capacity:!!n Gillick v West Norfolk and Wisbech AHA [1986]!n If and when a child under the age of 16 achieves a sufficient
understanding and intelligence to enable him/her to understand fully what is proposed, he/she is treated as having the capacity to consent!
n As the understanding required for different interventions will vary, a child under 16 my have the capacity to consent to some treatment, but not others!
!
Human Tissue Act 2004!
n Regulates storage and use of human tissues from living and
deceased!
n New offence of DNA theft!
n An offence to have have any human tissue for DNA analysis
without consent!
n Pts must consent to removal of tissue beyond dx & mx!
n Consent required for lawful retention of tissue from deceased!
Human Tissue Act 2004!
!Consent NOT required if!
n Using residual tissue from surgical procedure!
n Research on ‘residual tissue’ (above) if ethical
approval obtained and tissue donor not identifiable!
Human Tissue Act 2004!n Appropriate consent!
n Person if living!n Spouse!n Parent/child!n Sibling!n Grandparent!n Qualifying relatives !n Child of sibling!n Step parent!n Half sibling!n Longstanding friend!
Disease Participants/1000 DALYs Cancer 16.66
Nutrition 14.29
Psychiatric 0.23
Injuries 0.05
Disease burden and RCT evidence!
CHILDREN!What happens if child lacks capacity to make a decision?!
n The law allows a proxy or substitute consent, either by someone with parental responsibility or the Court!
n Parental responsibility includes an unmarried father with his name on the birth certificate for a birth after 1.12.2003!
n Any parental consent or refusal of consent must be given in the best interests of the child!
n Where more than one person has parental responsibility, each may act alone and without the other (with exceptions) !
Human Tissue Act 2004!n Incapacitated persons; consent deemed to be in place if:!
n Best interests of pt!n Allow research to take place in line with clinical trial Regulations
2004!n Allow storage tissue consistent with provisions of Mental
Capacity Act!
n Identify ‘at risk’ group!n Consent as many ‘at risk’ as possible in advance!n Hope enough develop emergency condition!
Emergency trials: Prospective Consent !
n Prospective consent!n Deferred consent!n Consent from authorised representative!
Emergency trials: alternatives !
n Identify ‘at risk’ group!n Consent as many ‘at risk’ as possible in advance!n Hope enough develop emergency condition!
Emergency trials: Prospective Consent !
n Proxy consent from relatives!n Allowed to consent to research (in advance)!n No mention of emergency research!!
Adults with Incapacity (Scotland)"Act 2000!
n Personal Legal Representative!n Next of kin!n May not be available!n May be too distressed to make decision!
n Professional Legal Representative!n Does not know the patient!n Cannot know patient’s wishes!n Cannot act on behalf of the patient!
The Medicines for Human Use"(Clinical Trials) Regulations 2004.!
n Despite limitations, it is the only way emergency trials can happen!
!
Professional Legal Representative!
n Despite limitations, it is the only way emergency trials can happen!
!
Professional Legal Representative!
!n Adequately planned protocol and recruitment
procedure!n Ethics committee approval!• Consent for continued participation!n Intervention intended to benefit subject!!!
Current protection in place for patient in emergency trials!
n Need consent enough ‘at risk’?!n Truly informed consent?!n How to identify those consented?!n Alter behaviour?!
Prospective Consent: Problems!
n Identify ‘at risk’ group!n 1% risk of event!n Need 100 recruits!n Must consent 10 000!
Prospective Consent: Need to consent enough ‘at risk’?!
E.G Young males are more at risk of traumatic brain injury - how would you prospectively consent this group?
n Individual likelihood of participation small!
n Risk given due consideration?!
Prospective Consent: Problems!
How would you identify those:!n Consented!n Not consented!n Refused?!
Prospective Consent: Identifying those consented!
n Hawthorne effect: subjects’ behaviour alters because of being observed not because of the intervention!
n May make recruiting more difficult!!!Doll, Peto et al. Mortality in relation to smoking: 40 years’ observations on male British doctors.
BMJ, 1994; 309: 901.!
Prospective Consent: Alter behaviour?!
n Hawthorne effect: subjects’ behaviour alters because of being observed not because of the intervention!
n May make recruiting more difficult!!!Doll, Peto et al. Mortality in relation to smoking: 40 years’ observations on male British doctors.
BMJ, 1994; 309: 901.!
Prospective Consent: Alter behaviour?!
n Accept that consent not possible!n Recruit suitable subjects!n Get consent later from patient, if recovers,
or from legally authorised representative (LAR)!
Deferred consent!
n Cannot consent to something that has!n already happened!!n How can you refuse if event in the past?!n What to do if patient dies or LAR not
available - use data or not?!n Will LAR know patients wishes?!
Deferred consent - problems!
n Directive 2001/20/EC – On the approximation of the laws regulations and administrative provisions of the member states relating to the implementation of good clinical practice on the conduct of clinical trial on medicinal products for human use.!
n Adults with Incapacity (Scotland) Act 2000!n The Medicines for Human Use (Clinical Trials)
Regulations 2004.!
LAR consent!
Directive 2001/20/EC – Article 5: Incapacitated adults and research!
n Informed consent of legal representative!n No mention of emergency research!
Directive 2001/20/EC!
International Conference on Harmonization -
ICH - GCP (Tripartite agreement) (1996) !
n Smt from joint committee from Japan - USA - UK!
n Ethical framework for drug trials to follow!n Main guidance in UK thro 1990s!n Aimed to standardize ethics and make things
easy!!n Initiative from pharmaceutical companies!!
ç
Legislation - Medicines for Human Use (clinical trials) Regulations 2004 -
Background!n UK implementation of EU CTD 2001/20/EC !n Aims to ensure the rights, safety and wellbeing of
subjects in trials into efficacy/safety of medicinal products in humans!n Does not cover surgery, devices or psychological tmt!
n Outline responsibilities of REC and researchers!n Outlines statutory controls of how clinical trials are to
be designed, carried out & reported!!!
Like 2001/20/EC and the ICH CGP the legislation involved limited academic input!
Legislation - Medicines for Human Use (clinical trials) Regulations 2004 - Key
points!
n Ethics – follows Declaration Helsinki!
n Prior approval, written consent !n Interests of patient outweigh benefits to society!n Provision made for incapable adults to consent !n If adult refused consent when having capacity they
can not be be entered to trial when capacity lost!n Requires risks to pt highlighted!n Expectation that trial will benefit pt / community!
