From Informed Consent to Enlightened Decision-Making From Informed Consent to Enlightened...

From Informed ConsentFrom Informed Consentto to

Enlightened Decision-MakingEnlightened Decision-Making

Jerry MenikoffJerry Menikoff

Disclaimer

The opinions expressed are those of the The opinions expressed are those of the

presenter and do not necessarily reflect presenter and do not necessarily reflect

the policy of the U.S. Department of the policy of the U.S. Department of

Health and Human Services.Health and Human Services.

Nuremberg CodeNuremberg Code

Person should have “sufficient Person should have “sufficient

knowledge . . . to make an knowledge . . . to make an

understanding and enlightened understanding and enlightened

decision” about participationdecision” about participation

Nuremberg CodeNuremberg Code

““Enlightened Decision” should presumably Enlightened Decision” should presumably

require sufficient information about three require sufficient information about three

major options patient could choose:major options patient could choose:

Standard CareStandard Care

Non-Standard CareNon-Standard Care

Being in a Research StudyBeing in a Research Study

The Past: Henry Beecher (1966)The Past: Henry Beecher (1966)

““Ethics and Clinical Research” in NEJMEthics and Clinical Research” in NEJM

50 Unethical Studies in major journals50 Unethical Studies in major journals

Only 2 Mentioned Getting ConsentOnly 2 Mentioned Getting Consent

““Ordinary patients will not knowingly risk Ordinary patients will not knowingly risk

their health or their life for the sake of their health or their life for the sake of

science”science”

Today: Federal RegulationsToday: Federal Regulations

Major elements of research consent:Major elements of research consent:

BenefitsBenefits-- “-- “A description of any benefits A description of any benefits

which may reasonably be expected”which may reasonably be expected” RisksRisks--“A description of any reasonably --“A description of any reasonably

foreseeable risks or discomforts”foreseeable risks or discomforts”

AlternativesAlternatives--“A disclosure of appropriate --“A disclosure of appropriate

alternative procedures that might be alternative procedures that might be

advantageous”advantageous”

Federal Regulations and Right to SueFederal Regulations and Right to Sue

Regulations do not actually create any Regulations do not actually create any

subject right to sue for wrongdoingsubject right to sue for wrongdoing

State State tort lawtort law does--a distinct system does--a distinct system

Tort of Tort of negligencenegligence: deviation from : deviation from

standard of carestandard of care

Inadequate informed consent as neg.Inadequate informed consent as neg.

Tort Law Rules for Informed ConsentTort Law Rules for Informed Consent

Informed Consent for Medical Care: Informed Consent for Medical Care:

ProfessionalProfessional standard v. standard v. Reasonable Reasonable

Person Person standard?standard?

Disclosure Duties Disclosure Duties higherhigher in research: in research:

deviating from accepted standardsdeviating from accepted standards

Apply Apply Reasonable PersonReasonable Person standard standard

Tort Law Rules for Informed ConsentTort Law Rules for Informed Consent

Provide information that reasonable person Provide information that reasonable person

would want to know in choosing would want to know in choosing

1) standard care1) standard care

2) nonstandard care2) nonstandard care

3) being in study3) being in study

Note similarity to Nuremberg Code Note similarity to Nuremberg Code

“enlightened decision”“enlightened decision”

Modern Day Problems with ConsentModern Day Problems with Consent

Questions to ExploreQuestions to Explore::

1. Do Consent Forms 1. Do Consent Forms CommonlyCommonly and and

SystematicallySystematically Fail to Give Subject Info Needed Fail to Give Subject Info Needed

to Make Informed Choice?to Make Informed Choice?

a. Information about what research isa. Information about what research is

b. Information specific to a studyb. Information specific to a study

Modern Day Problems with ConsentModern Day Problems with Consent

Questions to ExploreQuestions to Explore::

2. Is there a deeper flaw in the structure 2. Is there a deeper flaw in the structure

of consent forms, which mainly list of consent forms, which mainly list

benefits, risks and alternatives?benefits, risks and alternatives?

Meaning of being a research subjectMeaning of being a research subject

Regs require disclosing that “study Regs require disclosing that “study

involves research”involves research”

No disclosure of how research differs No disclosure of how research differs

from clinical carefrom clinical care

Miranda warning here makes more sense Miranda warning here makes more sense

than in criminal contextthan in criminal context


Disclose that patient’s well-being comes Disclose that patient’s well-being comes

second to answering research questionsecond to answering research question

Disclose that doctor no longer required to Disclose that doctor no longer required to

do what is best for persondo what is best for person


Disclose specific things that may not be in Disclose specific things that may not be in

person’s best interests, and why:person’s best interests, and why:

Extra tests and proceduresExtra tests and procedures

RandomizationRandomization

Adherence to Protocol (not indiv care)Adherence to Protocol (not indiv care)


Disclose that person will not be told of Disclose that person will not be told of

interim results, even if odds thousands-interim results, even if odds thousands-

to-one against treatment patient is gettingto-one against treatment patient is getting

Ironic that consent forms Ironic that consent forms dodo say you’ll be say you’ll be

told of new information “that may affect told of new information “that may affect

willingness to stay on study”willingness to stay on study”

Study-Specific InformationStudy-Specific Information

Are there certain categories of Are there certain categories of

information, specific to each study, that information, specific to each study, that

are commonly not being disclosed?are commonly not being disclosed?

1. 1. New Treatment – Efficacy InfoNew Treatment – Efficacy Info

Consent form: merely say it’s uncertain if Consent form: merely say it’s uncertain if

new treatment is better than standard carenew treatment is better than standard care

Protocol often has lengthy discussion—Protocol often has lengthy discussion—

yet not a word in consent form yet not a word in consent form

Info on prior studies? Related treatments? Info on prior studies? Related treatments?

Why new treatment might work or not?Why new treatment might work or not?


Q: Should Tentative Knowledge Q: Should Tentative Knowledge

Regarding New Treatment Be Given?Regarding New Treatment Be Given?

Ex:Ex: Metastatic Breast Ca StudyMetastatic Breast Ca Study

A: Chemo aloneA: Chemo alone

B: Chemo plus radiationB: Chemo plus radiation


Consent Form:Consent Form:

““Purpose is . . . Purpose is . . .

whether radiotherapy after chemowhether radiotherapy after chemo

will reduce risk of cancer recurrence.”will reduce risk of cancer recurrence.”


Protocol:Protocol:

““It appears that postmastectomyIt appears that postmastectomy

radiation [reduces] breast cancer deaths.”radiation [reduces] breast cancer deaths.”

Benefit magnitude unclear: Benefit magnitude unclear: 3 nodes 3 nodes

Q: Would reasonable woman care about difference Q: Would reasonable woman care about difference

between world where (a) no info on rad. effects, v. between world where (a) no info on rad. effects, v.

(b) radiation effective in 4+ nodes? (b) radiation effective in 4+ nodes?


NY Times article, 2004, discussed controversy, NY Times article, 2004, discussed controversy,

gave much info and treatment advice, e.g.:gave much info and treatment advice, e.g.:

““No question that rad. would reduce recurrence No question that rad. would reduce recurrence

rate by 2/3” but don’t know if increased survivalrate by 2/3” but don’t know if increased survival

““More and more [breast cancer experts]” are More and more [breast cancer experts]” are

sending their patients for radiation treatmentsending their patients for radiation treatment

2. 2. Standard Care – Efficacy InfoStandard Care – Efficacy Info

Should Should efficacy of standard careefficacy of standard care, ,

and and risks of new treatment not workingrisks of new treatment not working, ,

be disclosed?be disclosed?

Ex:Ex: Heart Surgery, high bleeding risk Heart Surgery, high bleeding risk

A: Standard fibrin sealantA: Standard fibrin sealant

B: Experimental fibrin sealantB: Experimental fibrin sealant


Not in Consent Form:Not in Consent Form:

Any info re Standard Care EfficacyAny info re Standard Care Efficacy

Info re consequences if new fibrin sealant Info re consequences if new fibrin sealant

is less effectiveis less effective


Would subjects view participation differently:Would subjects view participation differently:

Where standard care great, v.Where standard care great, v.

Where standard care sucks? Where standard care sucks?

Should specific risk of new treatment being less Should specific risk of new treatment being less

effective than standard care be mentioned and effective than standard care be mentioned and

consequences discussed in Risks section? consequences discussed in Risks section?

3. 3. Benefits InfoBenefits Info

A very common practice:A very common practice:Merely saying benefits are “uncertain”Merely saying benefits are “uncertain”

Ex: High cholesterol, on statinEx: High cholesterol, on statinA: New Drug X – 8 weeksA: New Drug X – 8 weeksB: PlaceboB: Placebo


Consent Form:Consent Form:

Benefits: “May have a good response . . . Benefits: “May have a good response . . .

or no direct benefit.”or no direct benefit.”

Q: What is chance that 8-week lowering of Q: What is chance that 8-week lowering of

cholesterol has much health effect? cholesterol has much health effect?


NCI “Gold Standard”:NCI “Gold Standard”: If you agree to take part in this study, If you agree to take part in this study,

there may or may not be there may or may not be

direct medical benefit to you.direct medical benefit to you.Benefit Likelihood – Benefit Likelihood – missingmissingBenefit Type – Benefit Type – missingmissing


Phase I StudyPhase I Study

To find highest safe doseTo find highest safe dose

Chance of benefit extremely lowChance of benefit extremely low

Subjects routinely overestimate Subjects routinely overestimate

benefits: the question is benefits: the question is why?why?


Special Article in NEJM, 12/2002Special Article in NEJM, 12/2002NIH Bioethics Center reviewed consent NIH Bioethics Center reviewed consent

formsformsConclusion: consent forms “unlikely to be Conclusion: consent forms “unlikely to be

primary source of misunderstanding”primary source of misunderstanding”Reason: Reason: the forms almost never promise the forms almost never promise

direct benefitdirect benefit


Study revealed 94% of the forms Study revealed 94% of the forms

“communicated uncertainty” about benefits“communicated uncertainty” about benefits

Is it OK to merely say “benefits uncertain,” and Is it OK to merely say “benefits uncertain,” and

not specifically say, e.g., “Likelihood of your not specifically say, e.g., “Likelihood of your

benefiting is near zero”?benefiting is near zero”?

Authors say yes: trial may involve approved Authors say yes: trial may involve approved

drugs also, may be psychological benefitsdrugs also, may be psychological benefits

4. 4. Alternatives InfoAlternatives Info

Should getting “experimental treatment”Should getting “experimental treatment” arm off-study be disclosed? arm off-study be disclosed?

Ex: Study of Tamoxifen & Raloxifene (STAR)Ex: Study of Tamoxifen & Raloxifene (STAR) Which prevents breast cancer best?Which prevents breast cancer best? 5-year randomized, double-blind 5-year randomized, double-blind 22,000 women 22,000 women


Tamoxifen: FDA approved, Tamoxifen: FDA approved,

prevents breast Caprevents breast Ca

Raloxifene: FDA approved for Raloxifene: FDA approved for

osteoporosis, not breast Caosteoporosis, not breast Ca


Consent FormConsent Form (FDA & NCI-approved):(FDA & NCI-approved):

Alternative: “ask your doctor to prescribe Alternative: “ask your doctor to prescribe

tamoxifen” or to remove both breaststamoxifen” or to remove both breasts

No mention of asking doctor for raloxifene, No mention of asking doctor for raloxifene,

though though >>1/3 physicians will sometimes 1/3 physicians will sometimes

prescribe it primarily to prevent breast Ca.prescribe it primarily to prevent breast Ca.


Non-disclosure argument:Non-disclosure argument:

It’s too risky an option to discloseIt’s too risky an option to disclose

STAR leader : “It’s too early to use STAR leader : “It’s too early to use

raloxifene to prevent cancer outside of a raloxifene to prevent cancer outside of a

clinical trial . . . We don’t yet know [its] clinical trial . . . We don’t yet know [its]

long-term benefits or risks.”long-term benefits or risks.”


Look at the Look at the risksrisks and and benefitsbenefits to a to a

person who is considering enrolling person who is considering enrolling

in STAR study:in STAR study:

RisksRisks: Getting “new” therapy outside : Getting “new” therapy outside

the study will in many (most?) cases the study will in many (most?) cases

involve no greater risks than getting involve no greater risks than getting

it in the studyit in the study


BenefitsBenefits: Experimental arm already in : Experimental arm already in

clinical equipoiseclinical equipoise with standard care, else with standard care, else

study is unethicalstudy is unethical

Honest disagreement about comparative Honest disagreement about comparative

merits merits

Thus, presumption that it is Thus, presumption that it is not not

unreasonableunreasonable to use experimental therapy to use experimental therapy

for given purposefor given purpose


Special benefits from off-study access:Special benefits from off-study access:

New York Times: “Few people sign on . . . New York Times: “Few people sign on . . .

out of pure altruism. They out of pure altruism. They want the want the

experimental drugs a study provides,experimental drugs a study provides,

often regarding them as ‘treatment’, even often regarding them as ‘treatment’, even

when their safety and effectiveness have when their safety and effectiveness have

not yet been proven.”not yet been proven.”


From From benefitsbenefits viewpoint of non-altruisitic viewpoint of non-altruisitic

subject wanting access to the subject wanting access to the

experimental therapy: experimental therapy:

a 50% chance at it in the study is worse a 50% chance at it in the study is worse

than a 100% chance outside the studythan a 100% chance outside the study

Thus, it is reasonable for subject to get Thus, it is reasonable for subject to get

direct access; disclosure is appropriate direct access; disclosure is appropriate


What if the new treatment What if the new treatment waswas too risky?: too risky?:

Assume getting a new therapy off-study is Assume getting a new therapy off-study is

so bad that no doctor should provide it; so bad that no doctor should provide it;

thenthen 50% chance of being exposed to this 50% chance of being exposed to this

“bad” option is presumably also bad “bad” option is presumably also bad

Thus, Thus, being in study is bad for subjectbeing in study is bad for subject

Then shouldn’t subject be Then shouldn’t subject be toldtold that? that?


Ex: Keyhole Surgery for Colon CancerEx: Keyhole Surgery for Colon Cancer Risk that keyhole surgery may not cure cancer as Risk that keyhole surgery may not cure cancer as

well as large incision surgerywell as large incision surgery ASCRS, 1994: Keyhole surgery is too risky, should ASCRS, 1994: Keyhole surgery is too risky, should

not be used outside a research studynot be used outside a research study Surveys show only 9-15% of colon surgeons would Surveys show only 9-15% of colon surgeons would

want this procedure done on themwant this procedure done on them Since 1994, there has been a randomized study, Since 1994, there has been a randomized study,

keyhole v. large incision keyhole v. large incision


For subject, possible benefits from keyhole surgeryFor subject, possible benefits from keyhole surgery—smaller incision and faster recovery—do not —smaller incision and faster recovery—do not outweigh higher risk of cancer recurrenceoutweigh higher risk of cancer recurrence

Thus, even though there is clinical equipoise, this is Thus, even though there is clinical equipoise, this is a “bad for the self-interested subject” studya “bad for the self-interested subject” study

Listing risks and benefits never conveys this Listing risks and benefits never conveys this information; here’s what a consent form information; here’s what a consent form should should say:say:


“ “The opinion of experts is that the risks to you from The opinion of experts is that the risks to you from participating in this study—the possibility of a participating in this study—the possibility of a greater chance of the cancer coming back– outweigh greater chance of the cancer coming back– outweigh the benefits. You should only be enrolling in this the benefits. You should only be enrolling in this study if you are willing to accept these greater health study if you are willing to accept these greater health risks in order to help determine what will be the best risks in order to help determine what will be the best care for future patients.care for future patients.

If you are interested in doing what is best for your If you are interested in doing what is best for your own health, you should own health, you should notnot be enrolling in this be enrolling in this study.”study.”

Putting it All TogetherPutting it All Together

Purpose of Informed Consent?Purpose of Informed Consent?

Let subject Let subject choose choose participate v. notparticipate v. not

ListingListing benefit, risks, alternatives is not enough benefit, risks, alternatives is not enough

to allow informed choiceto allow informed choice

We need to put this information together and We need to put this information together and

explain how to think about it—tell them which explain how to think about it—tell them which

are “good” or “bad” studies for them depending are “good” or “bad” studies for them depending

on a subject’s preferenceson a subject’s preferences

Putting it All TogetherPutting it All Together

Ask yourself:Ask yourself:

How many times have you seen a consent form How many times have you seen a consent form

which says, “Here are the reasons why you which says, “Here are the reasons why you

should perhaps decide NOT to participate in this should perhaps decide NOT to participate in this

study”?study”?

How odd that – given the consent process is How odd that – given the consent process is

about allowing choice – this is not statedabout allowing choice – this is not stated

Putting It All TogetherPutting It All Together

The Missing Crucial Piece:The Missing Crucial Piece: ComparingComparing risk-benefit relationship of being in study risk-benefit relationship of being in study to to

other optionsother options——

(a) getting standard care, or (a) getting standard care, or

(b) getting new care outside study(b) getting new care outside study Consent Forms never explain to subject how to think Consent Forms never explain to subject how to think

about deciding to enroll – about deciding to enroll – and why they might want to and why they might want to choose not to enroll! We often never even identify the choose not to enroll! We often never even identify the “clearly bad” studies.“clearly bad” studies.

This need only require a few extra sentences—This need only require a few extra sentences—highlighted in bold on the front page.highlighted in bold on the front page.

What Good Disclosure Would ReguireWhat Good Disclosure Would Reguire

Revisit Breast Cancer Study: Radiation or Not?Revisit Breast Cancer Study: Radiation or Not? If you are a person who If you are a person who wants to take all possible wants to take all possible

measures to reduce the likelihood of your cancer measures to reduce the likelihood of your cancer coming backcoming back, even at the risk of serious side effects , even at the risk of serious side effects from treatments that may actually be ineffective, you from treatments that may actually be ineffective, you might prefer to get the radiation treatment outside of might prefer to get the radiation treatment outside of this study. this study.

On the other hand, if you are very concerned On the other hand, if you are very concerned about the about the possibility of getting side effects from an unnecessary possibility of getting side effects from an unnecessary treatmenttreatment, one that is not yet proven to decrease the , one that is not yet proven to decrease the risk of the cancer coming back, you might want to avoid risk of the cancer coming back, you might want to avoid getting the radiation treatment instead of being in this getting the radiation treatment instead of being in this study.study.

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