Medical Ethics Year 2 The Ethics of Research. Medical Ethics Year 2 Medical Research vs. Medical Treatment Medical treatment is aimed at the welfare of

Medical Ethics Year 2

The Ethics The Ethics of of

ResearchResearch


Medical Research Medical Research vs.vs. Medical TreatmentMedical Treatment

Medical treatment is aimed at the welfare Medical treatment is aimed at the welfare of particular identifiable patients; the of particular identifiable patients; the

doctor’s clear obligation is to the patient.doctor’s clear obligation is to the patient.

Human biomedical research seeks to Human biomedical research seeks to improve the health and well being of improve the health and well being of

patients as a whole, so the obligation to patients as a whole, so the obligation to the patient remains but is in conflict with the patient remains but is in conflict with

other obligations and incentives.other obligations and incentives.


Medical ResearchMedical Research

Substantial rewardsSubstantial rewards Career promotion - Career promotion - ‘Publish or perish’‘Publish or perish’

Proven investigation skillsProven investigation skillsSalary increasesSalary increases

Financial incentives from pharmaceutical Financial incentives from pharmaceutical companies, e.g. renewed research fundingcompanies, e.g. renewed research funding

Respect from colleaguesRespect from colleagues



Unfortunately these competing Unfortunately these competing interests have at times put research interests have at times put research

participants’ welfare at risk.participants’ welfare at risk.



Medical research by its nature subjects Medical research by its nature subjects human participants to risky and human participants to risky and

sometimes invasive procedures for the sometimes invasive procedures for the sake of others.sake of others.

Why not research on animals, human Why not research on animals, human cells, computer modeling?cells, computer modeling?

The response of complex human The response of complex human organisms to biomedical intervention organisms to biomedical intervention

requires specific research.requires specific research.


Why Research Ethics?Why Research Ethics?

Medical research on humans raises difficult Medical research on humans raises difficult and important ethical and legal questions.and important ethical and legal questions.

The field of research ethics is devoted to the The field of research ethics is devoted to the systematic analysis of these questions to systematic analysis of these questions to

ensure that study participants are ensure that study participants are protected and, ultimately, that clinical protected and, ultimately, that clinical

research is conducted in a way that serves research is conducted in a way that serves the needs of such participants and of the needs of such participants and of

society as a whole.society as a whole.


Historical BackgroundHistorical Background

Consent Consent

The assumption that informed consent The assumption that informed consent is a pre-requisite to research on is a pre-requisite to research on

human subjects has not always been human subjects has not always been recognised.recognised.



Monstrous Nazi Medical trials by Monstrous Nazi Medical trials by German and Japanese doctors on German and Japanese doctors on unconsenting subjects, in utter unconsenting subjects, in utter

disregard of their rights and disregard of their rights and interests.interests.

Experiments involving hypothermia Experiments involving hypothermia (icy water immersion), twin studies, (icy water immersion), twin studies, typhus vaccination experiments, etc.typhus vaccination experiments, etc.



Subsequent to the trials and Subsequent to the trials and conviction of many of the medical conviction of many of the medical perpetrators at Nuremburg, the perpetrators at Nuremburg, the

Nuremburg Code (1947)Nuremburg Code (1947) was set up. was set up.


NurembergNuremberg CodeCode (1947)(1947)

The judgment by the war crimes The judgment by the war crimes tribunal at Nuremberg laid down tribunal at Nuremberg laid down 10 standards to which physicians 10 standards to which physicians must conform when carrying out must conform when carrying out experiments on human subjects.experiments on human subjects.

1. ‘1. ‘The voluntary consent of the The voluntary consent of the human subject is absolutely human subject is absolutely

essential…’essential…’



1. ‘1. ‘The voluntary consent of the The voluntary consent of the human subject is absolutely human subject is absolutely

essentialessential…The duty and …The duty and responsibility for ascertaining the responsibility for ascertaining the quality of the consent rests upon quality of the consent rests upon

each individual who initiates, each individual who initiates, directs, or engages in the directs, or engages in the

experiment…’experiment…’



2.2. ‘…‘…fruitful results for the good of fruitful results for the good of society, unprocurable by other methods society, unprocurable by other methods

or means…or means…

3.3. ……so designed and based on (prior) so designed and based on (prior) knowledge …that the anticipated knowledge …that the anticipated

results justify the performance of the results justify the performance of the experiment.experiment.

4.4. ……so conducted to avoid all unnecessary so conducted to avoid all unnecessary physical and mental suffering and physical and mental suffering and

injury.injury.


Nuremberg Code (1947)Nuremberg Code (1947)

5.5. No experiment…(if) there is…reason to No experiment…(if) there is…reason to believe that death or disabling injury will believe that death or disabling injury will occur…except…where the experimental occur…except…where the experimental

physicians also serve as subjects. physicians also serve as subjects.

6.6. The degree of risk…should never exceed …the The degree of risk…should never exceed …the humanitarian importance of the problem to be humanitarian importance of the problem to be

solved…solved…

7.7. Proper preparations…and adequate Proper preparations…and adequate facilities…facilities…



8.8. ……conducted only by scientifically conducted only by scientifically qualified persons. The highest degree of qualified persons. The highest degree of

skill and care… skill and care…

9.9. During the course of the experiment the During the course of the experiment the human subject should be at liberty to human subject should be at liberty to

bring the experiment to an end…bring the experiment to an end…

10.10. ……the scientist in charge must be the scientist in charge must be prepared to terminate the experiment prepared to terminate the experiment

at any stage, if he has cause to at any stage, if he has cause to believe… believe…


Declaration of Helsinki Declaration of Helsinki (1964)(1964)

World Medical Association (WMA)World Medical Association (WMA)

To address medical research enrolling To address medical research enrolling patients as subjects.patients as subjects.

Probably the most influential document Probably the most influential document governing research worldwidegoverning research worldwide

Amended 2008Amended 2008



Added 3 important points to Nuremberg CodeAdded 3 important points to Nuremberg Code

1.1. Distinction between therapeutic research Distinction between therapeutic research (aims to benefit patients) and non-therapeutic (aims to benefit patients) and non-therapeutic

research (aims to generate scientific research (aims to generate scientific knowledge)knowledge)

2.2. An institutional mechanism should be in place An institutional mechanism should be in place to ensure that the main ethical principles to ensure that the main ethical principles

were followed.were followed.

3.3. Provision of proxy consent by family members Provision of proxy consent by family members when subjects could not consent themselves.when subjects could not consent themselves.



2 years after the Helsinki declaration a paper in 2 years after the Helsinki declaration a paper in the the NEJM NEJM (1966) by Henry K. Beecher, (1966) by Henry K. Beecher,

Harvard anaesthetist indicated that healthcare Harvard anaesthetist indicated that healthcare professionals in other countries were found to professionals in other countries were found to have conducted research unethically on their have conducted research unethically on their

research subjects.research subjects.

22 studies22 studies

Hundreds of the patients did not know the risks Hundreds of the patients did not know the risks of the studies they were participating in and of the studies they were participating in and hundreds more didn’t even know they were hundreds more didn’t even know they were

subjects of research at all.subjects of research at all.1Beecher, ‘Ethics and Clinical research’, NEJM (1966)


Case 1Case 1To improve the understanding To improve the understanding

of diseaseof diseaseMelanoma tissue was transplanted from a Melanoma tissue was transplanted from a daughter to her volunteering and informed daughter to her volunteering and informed

mother, mother, ‘in the hope of gaining a little better ‘in the hope of gaining a little better understanding of cancer immunity and in the understanding of cancer immunity and in the hope that the production of tumor antibodies hope that the production of tumor antibodies

might be helpful in the treatment of the might be helpful in the treatment of the cancer patient.’ cancer patient.’

The daughter died the next day (her condition The daughter died the next day (her condition had been recognised as terminal). The mother had been recognised as terminal). The mother died from metastatic melanoma 451 days post died from metastatic melanoma 451 days post

transplantationtransplantation..1Beecher, ‘Ethics and Clinical research’, NEJM (1966)


Case 2Case 2Known effective medicine Known effective medicine

withheldwithheldRelapse rate of typhoid feverRelapse rate of typhoid fever

Chloramphenicol had been shown to be an Chloramphenicol had been shown to be an effective treatment (halving typhoid effective treatment (halving typhoid

mortality)mortality)

408 charity cases with typhoid fever408 charity cases with typhoid fever

251251 given chloramphenicol (20 ( 7.97%) died) given chloramphenicol (20 ( 7.97%) died)

157157 symptomatic treatment only (36 (22.9%) symptomatic treatment only (36 (22.9%) died)died)

i.e. 23 patients died who should not have.i.e. 23 patients died who should not have.

1Beecher, ‘Ethics and Clinical research’, NEJM (1966)


Case 3Case 3 Minimum blood flow Minimum blood flow

requirements for cerebral requirements for cerebral circulationcirculationTo determine cerebral haemodynamic and metabolic To determine cerebral haemodynamic and metabolic

changes…before and during acute reductions in arterial changes…before and during acute reductions in arterial pressure induced by drug administration +/or postural pressure induced by drug administration +/or postural adjustments.adjustments.

N =48 (hospitalised), age 20’s to 90’s, various B.P’s inc. N =48 (hospitalised), age 20’s to 90’s, various B.P’s inc. malignant hypertension / Femoral arteries and jugular malignant hypertension / Femoral arteries and jugular veins cannulated.veins cannulated.

Signs of cerebral insufficiency were confusion, non-Signs of cerebral insufficiency were confusion, non-responsive state, responsive state,

By altering the tilt of the patient signs of confusion could be By altering the tilt of the patient signs of confusion could be altered in seconds from alertness to confusion,…the altered in seconds from alertness to confusion,…the patient was maintained in this state for the remainder of patient was maintained in this state for the remainder of the experimentthe experiment

With the onset of collapse, CO and RVP decreased sharply…With the onset of collapse, CO and RVP decreased sharply…since signs of cerebral insufficiency developed without since signs of cerebral insufficiency developed without evidence of coronary insufficiency… evidence of coronary insufficiency… ‘the brain may be ‘the brain may be more sensitive to acute hypotension than the heart.’more sensitive to acute hypotension than the heart.’ 1Beecher, ‘Ethics and Clinical research’, NEJM (1966)


Case 4Case 4Does ureteral reflux occur in Does ureteral reflux occur in

the normal bladder?the normal bladder?Vesico-ureterography was performed on Vesico-ureterography was performed on

20 new born babies (<48 hrs old). 20 new born babies (<48 hrs old).

Catheterisation and multiple X-ray Catheterisation and multiple X-ray exposure while bladder filling and exposure while bladder filling and

voiding. Multiple spot x-rays taken to voiding. Multiple spot x-rays taken to record presence or absence of record presence or absence of

ureteral reflux. None was found.ureteral reflux. None was found.

Effects of multiple X-Ray exposure long Effects of multiple X-Ray exposure long term???term???



Tuskegee Syphilis StudyTuskegee Syphilis Study

1932 - 19721932 - 1972Epidemiological Study - The Natural History of Epidemiological Study - The Natural History of

SyphilisSyphilisStudy of a cohort of African-American men with Study of a cohort of African-American men with

syphilis.syphilis.The men were either not told or were misled about The men were either not told or were misled about

the nature of their disease the nature of their disease They were denied treatment and discouraged from They were denied treatment and discouraged from

seeking alternative advice or treatment. seeking alternative advice or treatment. Even when effective treatment for syphilis became Even when effective treatment for syphilis became

available form the 1940’s, they were not offered available form the 1940’s, they were not offered this. They were followed up until 1972, when the this. They were followed up until 1972, when the

study was closed owing to public outcry.study was closed owing to public outcry.


Belmont Report (1979)Belmont Report (1979)US National Commission for the Protection of US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Human Subjects of Biomedical and Behavioral

ResearchResearch

3 guiding principles for ethical 3 guiding principles for ethical researchresearch

1.1. Respect for personsRespect for persons

2.2. BeneficenceBeneficence – favorable risk-benefit – favorable risk-benefit ratio. (includes Nonmaleficence) ratio. (includes Nonmaleficence)

3.3. JusticeJustice – equitable distribution of the – equitable distribution of the burdens and benefits of research; must burdens and benefits of research; must not exploit the vulnerable nor exclude not exploit the vulnerable nor exclude

the eligible who may benefitthe eligible who may benefit


NurembergNuremberg Code (1947)Code (1947)

The judgment by the war crimes tribunal at The judgment by the war crimes tribunal at Nuremberg laid down 10 standards to Nuremberg laid down 10 standards to which physicians must conform when which physicians must conform when carrying out experiments on human carrying out experiments on human

subjects.subjects.

1. ‘1. ‘The voluntary consent of the human The voluntary consent of the human subject is absolutely essentialsubject is absolutely essential…The duty …The duty and responsibility for ascertaining the and responsibility for ascertaining the quality of the consent rests upon each quality of the consent rests upon each

individual who initiates, directs, or individual who initiates, directs, or engages in the experiment…’engages in the experiment…’



2.2. ‘…‘…fruitful results for the good of fruitful results for the good of society, unprocurable by other methods society, unprocurable by other methods

or means…or means…

3.3. ……so designed and based on (prior) so designed and based on (prior) knowledge …that the anticipated knowledge …that the anticipated

results justify the performance of the results justify the performance of the experiment.experiment.

4.4. ……so conducted to avoid all unnecessary so conducted to avoid all unnecessary physical and mental suffering and physical and mental suffering and

injury.injury.



5.5. No experiment…(if) there is…reason to No experiment…(if) there is…reason to believe that death or disabling injury will believe that death or disabling injury will occur…except…where the experimental occur…except…where the experimental

physicians also serve as subjects. physicians also serve as subjects.

6.6. The degree of risk…should never exceed …the The degree of risk…should never exceed …the humanitarian importance of the problem to be humanitarian importance of the problem to be

solved…solved…

7.7. Proper preparations…and adequate Proper preparations…and adequate facilities…facilities…



Added 3 important points to Nuremberg CodeAdded 3 important points to Nuremberg Code

1.1. Distinction between therapeutic research Distinction between therapeutic research (aims to benefit patients) and non-therapeutic (aims to benefit patients) and non-therapeutic

research (aims to generate scientific research (aims to generate scientific knowledge)knowledge)

2.2. An institutional mechanism should be in place An institutional mechanism should be in place to ensure that the main ethical principles to ensure that the main ethical principles

were followed.were followed.

3.3. Provision of proxy consent by family members Provision of proxy consent by family members when subjects could not consent themselves.when subjects could not consent themselves.


CIOMS (2002)CIOMS (2002)

Council for International Council for International Organisations of Medical Sciences Organisations of Medical Sciences

CIOMSCIOMS

Addresses definition of what is Addresses definition of what is medical researchmedical research


Ethics Review Committee / Ethics Review Committee / BoardBoard

Common commitment of ensuring the protection of Common commitment of ensuring the protection of the rights and welfare of the research subjects.the rights and welfare of the research subjects.

Proposals involving research on human subjects Proposals involving research on human subjects should be submitted to the ‘local’ ethics review should be submitted to the ‘local’ ethics review committee or board of the institution or hospital committee or board of the institution or hospital

for consideration and approval. for consideration and approval. Ethical issues must permeate research and must Ethical issues must permeate research and must

guide research design, guide research design, i.e.i.e. in the first stages of in the first stages of planning.planning.

Increasingly theses boards and committees are Increasingly theses boards and committees are being consulted in the planning stages of being consulted in the planning stages of

research.research.


A Research Experiment is either A Research Experiment is either Ethical from the beginning or Ethical from the beginning or

not. It does not become so after not. It does not become so after the event!the event!

‘‘Ends Do Not Justify Means’Ends Do Not Justify Means’


Dual role of Clinician and Dual role of Clinician and ResearcherResearcher

Doctors have a duty to protect their Doctors have a duty to protect their patients from harm, but medical patients from harm, but medical

research exposes them to risk of harm, research exposes them to risk of harm, then it seems a doctor has a duty to then it seems a doctor has a duty to

discourage them from participating in discourage them from participating in research.research.

However this conflicts with the doctor’s However this conflicts with the doctor’s duty as a researcher to promote science duty as a researcher to promote science

and the health of future patients.and the health of future patients.



‘‘When may a society, actively or When may a society, actively or by acquiescence, expose some of by acquiescence, expose some of its members to harm in order to its members to harm in order to

seek benefits for them, for seek benefits for them, for others, or for society as a others, or for society as a

whole?’ whole?’

(Jay Katz, 1993)(Jay Katz, 1993)



Kant’s second formulation of the Kant’s second formulation of the categorical imperative, in human categorical imperative, in human

biomedical researchbiomedical research

‘ ‘ researchers have a duty to treat these researchers have a duty to treat these subjects not only as means, but also subjects not only as means, but also

as ends-in-themselves.’as ends-in-themselves.’11

1Glannon, Biomedical Ethics(2005), OUP


TrialsTrials

Randomised clinical trials are a Randomised clinical trials are a standard form of medical research.standard form of medical research.

Efficacy of certain treatments, Efficacy of certain treatments,

e.g.e.g.

Is Treatment Is Treatment AA better than Placebo? better than Placebo?

Is Treatment Is Treatment AA better than Treatment better than Treatment BB??


4 Phase Trials4 Phase Trials

Prior animal trialsPrior animal trials

Phase I non-therapeutic drug trialPhase I non-therapeutic drug trial

Toxicity studies – i.e. the highest dose human can Toxicity studies – i.e. the highest dose human can tolerate. tolerate.

Usually healthy volunteers (except Phase 1 trials of Usually healthy volunteers (except Phase 1 trials of cancer drugs where patients have already exhausted cancer drugs where patients have already exhausted

all other treatments and have a life span of a few all other treatments and have a life span of a few months only).months only).

Altruistic volunteers or monetary compensation Altruistic volunteers or monetary compensation seeking?seeking?

Desperate patients with false hopes?Desperate patients with false hopes?



Phase II non-therapeutic trialPhase II non-therapeutic trial

Optimal dosing regimeOptimal dosing regime

Testing for experimental conditions for Testing for experimental conditions for Phase III to allow definitive resultPhase III to allow definitive result

Specify end-points Specify end-points (e.g.5 yr SR)(e.g.5 yr SR)

Note: Phase I & II non-therapeutic hence Note: Phase I & II non-therapeutic hence researchers main moral obligation is to researchers main moral obligation is to protect from harm (risk of serious side-protect from harm (risk of serious side-

effects)effects)



Phase III therapeutic trialPhase III therapeutic trial

Largest number of patientsLargest number of patients

May be therapeutic in natureMay be therapeutic in nature

Is the treatment effective and what Is the treatment effective and what are the side-effectsare the side-effects



Phase IV therapeutic trialPhase IV therapeutic trial

Post approval Post approval (by e.g. FDA)(by e.g. FDA) and marketing and marketing

Monitor side-effects and gather additional Monitor side-effects and gather additional information, e.g. broader usage.information, e.g. broader usage.

Note: Phase III & IV therapeutic hence Note: Phase III & IV therapeutic hence researchers main moral obligation is to researchers main moral obligation is to

ensure appropriate risk-benefit ratioensure appropriate risk-benefit ratio



Gold Standard TrialGold Standard Trial

1.1. ProspectiveProspective

2.2. RandomisedRandomised

3.3. Placebo controlledPlacebo controlled

4.4. Blinded / Double blindedBlinded / Double blinded


EquipoiseEquipoise

Randomised clinical trials are a Randomised clinical trials are a standard form of medical research.standard form of medical research.

Patients are randomly assigned to one Patients are randomly assigned to one of the arms of the trial. of the arms of the trial.


EquipoiseEquipoise

Widely accepted that randomised Widely accepted that randomised clinical trials, to be morally sound, clinical trials, to be morally sound,

require require equipoiseequipoise, that is , that is uncertaintyuncertainty as to the merits of each arm of the as to the merits of each arm of the

trial. trial.

Treatment Treatment AA vs. Placebo? vs. Placebo?

Treatment Treatment AA vs. Treatment vs. Treatment BB??


EquipoiseEquipoise

Equipoise is uncertainty in the Equipoise is uncertainty in the expert medical expert medical communitycommunity, , not in thenot in the researcherresearcher..

(Benjamin Freedman, ‘Equipoise and the Ethics of Clinical Research’ (Benjamin Freedman, ‘Equipoise and the Ethics of Clinical Research’ NEJM, 1987).NEJM, 1987).

The traditional role of the doctor is The traditional role of the doctor is incompatibleincompatible with this. The doctor's duty is first and foremost with this. The doctor's duty is first and foremost

to each individual patient. Doctors cannot act to each individual patient. Doctors cannot act for the public good and for the good of each for the public good and for the good of each

patient. patient. (Samuel Hellman, ‘The Patient and the Public Good', Nature (Samuel Hellman, ‘The Patient and the Public Good', Nature

Medicine(1985)).Medicine(1985)).


RandomisationRandomisation

Similar concerns for the doctor, Similar concerns for the doctor,

however again if there is a however again if there is a genuine uncertainty about the genuine uncertainty about the efficacy of a certain treatment, efficacy of a certain treatment, then a randomised controlled then a randomised controlled trial is the best way to yield trial is the best way to yield

objectively valid results.objectively valid results.



Treating the patient as a means for the Treating the patient as a means for the sake of generating scientific knowledgesake of generating scientific knowledge

But alsoBut also

Treating the patient as an end by obtaining Treating the patient as an end by obtaining consent to participate in the trial and consent to participate in the trial and

ensuring the potential risks are ensuring the potential risks are commensurate with the potential commensurate with the potential

benefits.benefits.

Physician-Researcher dual role is thus Physician-Researcher dual role is thus fulfilledfulfilled



Early Breast CancerEarly Breast CancerLumpectomy Lumpectomy vs.vs. Mastectomy Mastectomy

Uncertainty allows valid entry of patient Uncertainty allows valid entry of patient into clinical trial comparing the two into clinical trial comparing the two

surgical approaches.surgical approaches.Thus the surgeon is treating her patients Thus the surgeon is treating her patients

as means in deriving valid scientific as means in deriving valid scientific data but also as ends in offering each data but also as ends in offering each patient a 50% chance of receiving the patient a 50% chance of receiving the

best treatment, as yet unknown.best treatment, as yet unknown.


PlaceboPlacebo

Placebo-controlled trials are Placebo-controlled trials are scientifically more robust than scientifically more robust than

active-controlled trials.active-controlled trials.

Shorter durationShorter duration

However However sick patientssick patients in the placebo in the placebo arm of the trial are not receiving arm of the trial are not receiving any treatment for the duration of any treatment for the duration of

the trial, hence exposed to greater the trial, hence exposed to greater risks.risks.


PlaceboPlacebo

Declaration of Helsinki 2000 revision – Declaration of Helsinki 2000 revision – new treatments must be tested new treatments must be tested

against ‘best available’ treatments against ‘best available’ treatments unless there is no proven treatment unless there is no proven treatment

exists.exists.

This approach is supported by This approach is supported by deontological and consequentialist deontological and consequentialist arguments, in considering the best arguments, in considering the best

interests of the sick patient, although interests of the sick patient, although scientifically it may not be the most scientifically it may not be the most

sound approach.sound approach.


PlaceboPlacebo

Placebo controlled trials for Placebo controlled trials for surgical procedures have clear surgical procedures have clear

ethical difficultiesethical difficulties


PlaceboPlacebo

19991999 Parkinson’s fetal cell implant trialParkinson’s fetal cell implant trialPatients in the intervention group Patients in the intervention group

- General anaesthetic General anaesthetic - Burr holes penetrating the inner Burr holes penetrating the inner

cortex of the brain cortex of the brain - Fetal tissue implantedFetal tissue implanted

- Low dose immunosuppressive drug Low dose immunosuppressive drug xx 6/126/12


PlaceboPlacebo

19991999 Parkinson’s fetal cell implant trialParkinson’s fetal cell implant trial

Patients in the control group Patients in the control group - General anaesthetic General anaesthetic

- Burr holes not penetrating the Burr holes not penetrating the cortex of the brain cortex of the brain

- No fetal tissue implantedNo fetal tissue implanted- Low dose immunosuppressive drug Low dose immunosuppressive drug

xx 6/126/12 -


PlaceboPlacebo

Did the significant risks in this study to Did the significant risks in this study to both groups outweigh the potential both groups outweigh the potential

benefits to them or to future patients?benefits to them or to future patients?

Does this contravene the duty of care of Does this contravene the duty of care of the doctor not to enroll their patient the doctor not to enroll their patient

in this type of study?in this type of study?

Is the ‘sham’ surgery unethical in its Is the ‘sham’ surgery unethical in its deliberate deceit of the patient by the deliberate deceit of the patient by the

surgeon?surgeon?



Doctors have a duty to protect their Doctors have a duty to protect their patients from harm, but medical patients from harm, but medical

research exposes them to risk of harm, research exposes them to risk of harm, then it seems a doctor has a duty to then it seems a doctor has a duty to

discourage them from participating in discourage them from participating in research.research.

However this conflicts with the doctor’s However this conflicts with the doctor’s duty as a researcher to promote science duty as a researcher to promote science

and the health of future patients.and the health of future patients.


Doctor-researcher must strike a Doctor-researcher must strike a delicate balance between the two delicate balance between the two obligations to patients-subjects.obligations to patients-subjects.

Particularly difficult with non-Particularly difficult with non-therapeutic research, where the therapeutic research, where the

patient derives no benefit.patient derives no benefit.

The benefit is for future patients.The benefit is for future patients.



Deontological approach - respect the Deontological approach - respect the patient’s right not to be harmed.patient’s right not to be harmed.

Consequentialist approach – more Consequentialist approach – more weight to the scientific knowledge to weight to the scientific knowledge to

be gained by the research be gained by the research participation.participation.



Fiduciary nature of the doctor-patient Fiduciary nature of the doctor-patient relationship - is it the same for the relationship - is it the same for the

researcher- subject?researcher- subject?

Do not harmDo not harm

Respect and promote autonomous Respect and promote autonomous decision makingdecision making



Research Ethics Research Ethics CommitteesCommittees

Must act to ensure five conditions are Must act to ensure five conditions are adhered to in any research protocol adhered to in any research protocol

before them.before them.


1. Consent1. Consent

Normally patients will not knowingly risk Normally patients will not knowingly risk their health or life for the sake of science.their health or life for the sake of science.

Capacity to understand Capacity to understand

(placebo, randomisation, etc.)(placebo, randomisation, etc.)

All hazards are made clearAll hazards are made clear

If unknown this too must be made clearIf unknown this too must be made clear



Problems with ConsentProblems with Consent

‘‘A far more dependable safeguard A far more dependable safeguard than consent is the presence of a than consent is the presence of a truly responsible investigator’ truly responsible investigator’

(Beecher, 1966).(Beecher, 1966).



Informed ConsentInformed Consent

Is this enough?Is this enough?



Swedish HIV study Swedish HIV study

(prior to definitive AIDS treatments (prior to definitive AIDS treatments becoming available)becoming available)

The study drug, which promises to delay The study drug, which promises to delay the onset of AIDS in HIV infected the onset of AIDS in HIV infected patients, carries a risk of death of patients, carries a risk of death of

1/500.1/500.

Patients fully informed of the relevant facts Patients fully informed of the relevant facts and risks.and risks.




Is there a difference between doctors Is there a difference between doctors allowing patients to make foolish or allowing patients to make foolish or unreasonable choices themselves, unreasonable choices themselves, and actively putting those choices and actively putting those choices before patients that they regard as before patients that they regard as

foolish, irrespective of how foolish, irrespective of how ‘informed’ those patients are. ‘informed’ those patients are.




Participation to please the doctorParticipation to please the doctor

Participation because of false hopesParticipation because of false hopes

Is voluntary informed consent ever Is voluntary informed consent ever present in medical research?present in medical research?




Difficulties but Difficulties but ‘it is absolutely ‘it is absolutely essential to strive for it for moral, essential to strive for it for moral,

sociologic and legal reasons.’sociologic and legal reasons.’11



2. Risk-Benefit Ratio2. Risk-Benefit Ratio

Favourable risk-benefit ratioFavourable risk-benefit ratio

The subject must not be exposed to The subject must not be exposed to undue risk and the potential benefit undue risk and the potential benefit

of learning whether a drug or of learning whether a drug or surgical procedure works must be surgical procedure works must be

worth any potential risk to the worth any potential risk to the subjects.subjects.



3. Equitable selection of 3. Equitable selection of patientspatients

Equitable selection of subjects that Equitable selection of subjects that rules out any exploitation and rules out any exploitation and

adequately represents both sexes adequately represents both sexes and all social groups.and all social groups.



4. Privacy of subjects4. Privacy of subjects

Privacy and confidentiality of subjects Privacy and confidentiality of subjects must be protected.must be protected.



5. Confidentiality of data5. Confidentiality of data

Research data must be kept Research data must be kept confidentialconfidential



Scientifically soundScientifically sound

A research study must be sufficiently A research study must be sufficiently well designed such that the well designed such that the

maximum results can be gleaned maximum results can be gleaned from the research, ensuring that from the research, ensuring that

patients have not undergone risks patients have not undergone risks and discomfort in vain.and discomfort in vain.

Obligation to ensure that the study Obligation to ensure that the study findings are valid and replicable.findings are valid and replicable.


Scientifically soundScientifically sound

Careful study design and executionCareful study design and execution

such that such that

1.1. The research question is answered The research question is answered reliably and efficientlyreliably and efficiently

2.2. Sufficient numbers are enrolled to Sufficient numbers are enrolled to make the results meaningfulmake the results meaningful

3.3. Compliance must be ensured.Compliance must be ensured.


Case 5Case 511

Dr. X is a GP, with a special interest in Dr. X is a GP, with a special interest in COPD. He is contacted by the COPD. He is contacted by the

coordinator of a study evaluating a coordinator of a study evaluating a promising new treatment for COPD. promising new treatment for COPD.

He is asked to provide names of He is asked to provide names of potentially eligible patients and will potentially eligible patients and will

receive a fee of € 100 per name. receive a fee of € 100 per name.

1Meslin, EM, Dickens BM, Research Ethics, Chapter 25, Cambridge Textbook of Bioethics (CUP 2008)


Case 5Case 511

Finder’s fee ethically and legally Finder’s fee ethically and legally objectionable; remuneration for time objectionable; remuneration for time

spent acceptablespent acceptable

In breach of fiduciary duty and In breach of fiduciary duty and conflicted if provide confidential conflicted if provide confidential medical info for personal gainmedical info for personal gain



Case 6Case 611

Dr. Y, a psychiatrist in private practice is Dr. Y, a psychiatrist in private practice is asked by a pharmaceutical company asked by a pharmaceutical company

conducting research on a new antipsychotic conducting research on a new antipsychotic drug drug

Acutely psychotic patients, No prev. hxAcutely psychotic patients, No prev. hxAdmission for 8 weeksAdmission for 8 weeks

No treatment for the duration for the placebo No treatment for the duration for the placebo armarm

Only treatment with the new drug for the Only treatment with the new drug for the active armactive arm

Consent or proxyConsent or proxy1Meslin, EM, Dickens BM, Research Ethics, Chapter 25, Cambridge Textbook of Bioethics (CUP 2008)


Case 6Case 611

Consent alone is insufficientConsent alone is insufficient

There must be a favourable balance of There must be a favourable balance of benefits and harmsbenefits and harms

Clinical equipoiseClinical equipoise



Medical researchMedical research

Widely agreed that medical research Widely agreed that medical research can be conducted on autonomous can be conducted on autonomous persons, who have given informed persons, who have given informed

consent.consent.

However what about human infants However what about human infants and children, the learning disabled, and children, the learning disabled,

human embryos?human embryos?


Documents

Medical Ethics Year 2 The Ethics of Research. Medical Ethics Year 2 Medical Research vs. Medical Treatment Medical treatment is aimed at the welfare of