Good Research, Bad Choices? Mary Coombs. What Makes Something Research Rather Than Treatment?

Good Research, Bad Choices?

Mary Coombs

What Makes Something Research Rather Than Treatment?

What Makes Something Research Rather Than Treatment?

Primary Goal is to Answer a Research Question

What Makes Something Research Rather Than Treatment?

Subject welfare isn’t primary goal: “risks to subjects must be reasonable in

relation to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result”

What Makes Something Research Rather Than Treatment?

Decisions are based on protocol in first instance

Not on contextual best interests of this person

What Makes Something Research Rather Than Treatment?

Usually requires testing and procedures beyond those needed for treatment

What Makes Something Research Rather Than Treatment?

Usually/ ideally is RCT Neither subject nor researcher know if

is getting treatment A or treatment B

Proposed: “The main purpose of a clinical trial is to benefit future patients rather than the patients in the trial”

Do you think this is true?

Proposed: “The main purpose of a clinical trial is to benefit future patients rather than the patients in the trial”

What did doctors at a (Boston-based) academic institution think?

Proposed: “The main purpose of a clinical trial is to benefit future patients rather than the patients in the trial”

What did doctors at a (Boston-based) academic institution think?

Yes: 45.9%Unsure: 29.5%No: 24.6%

This misunderstanding is common enough to have a name:

Therapeutic MisconceptionTherapeutic Misconception

Law and Ethics of Treatment

(a very summary summary!!)

Law and Ethics of Treatment

Option A: Standard TreatmentInformed Consent needed

Law and Ethics of Treatment

Option B: Reasonable Experimental TreatmentMore Detailed Informed Consent needed

Law and Ethics of Treatment

Option C: Unreasonable Experimental TreatmentNot permitted“Consent” Irrelevant

Law and Ethics of Treatment

There is Potential Tort Liability if 1) there is a bad outcome and2) there was

a. Unreasonable Experimental Treatment or

b. Insufficient Informed Consent or

c. Execution of Treatment fell below standard of care

How Can Research Study be a “Bad Choice”? Phase One Trial

Consider:Risk to subjectBenefit to subjectBenefit to knowledge/future patients

How Can it be a “Bad Choice”? Phase One Trial

Risk to subject Significant: more toxic dose than

previously given to humans

How Can it be a “Bad Choice”? Phase One Trial

Benefit to subject? Minor in fact Protocol not designed to test efficacy

How Can it be a “Bad Choice”? Phase One Trial

Benefit to knowledge/future patients? Subjects say are doing to find a cure for

themselves Are either altruistic or misunderstand the

“free rider” option

Downsides of being a Subject: Other Clinical Trials

Apart from Randomization Rigidity of protocol Risks/Inconveniences of Additional

Testing Not told of interim results

Upsides of being a Subject: Other Clinical Trials

Apart from Randomization Access to better quality care than P

might otherwise obtain Academic medical center trials Effect of limits on health insurance

Upsides of being a Subject: Other Clinical Trials

Apart from Randomization Possible Access to Drug/Treatment not

otherwise available If new drug If (some) doctors won’t provide off-label If new technique not available outside trial

setting

Upsides/Downsides of being a Subject:Randomization

Must be “clinical equipoise” What might be differences between

standard and new treatment?

Possible Differences [to be tested by study]

Effectiveness Expected Mild-to-Moderate Side

Effects Level of Risk of Serious Side Effects Convenience Cost

Possible Outcomes [after study]

New treatment is clearly as good or better on all dimensions

Standard treatment is clearly as good or better on all dimensions

Two treatments are in equipoise: incommensurable (known) differences

Clinician decisions [after study]

New treatment is clearly as good or better on all dimensions: USE NEW

Standard treatment is clearly as good or better on all dimensions: USE STANDARD

Clinician decisions [after study]

Two treatments are in equipoise: incommensurable (known) differences Choose what is best given specifics of

this patient Engage patient to help choose given

subjective preferences E.g. risk vs. efficacy E.g. cost vs mild/moderate likely side

effects

Clinician decisions [before study](if new treatment available outside study

Two treatments are in equipoise: incommensurable (unknown) differencesChoose what is best given specifics of this patientEngage patient in choice given subjective preferences

E.g. risk vs. efficacyE.g. cost vs mild/moderate likely side effects

Is informed consent the answer to the “bad choices/good study” dilemma?

Are people free to be altruistic?Are people free to make “bad choices”?Should we be skeptical that bad choices are freely made and fully informed?

Does Informed Consent Form Matter?

written documentation matters Research form is more important

than treatment form Research form is easier to prepare

than treatment form Liability: “I always tell people; I

must have told Ms. X”

What might a subject want to know?

That is a research study Potential future benefits of research study Intervention being studied Alternative [standard care? placebo?] Are there third alternatives available? Risks of Standard Care Risks of Proposed New Treatment

What might a subject want to know?

Benefits of Standard Care Benefits of New Treatment Risks/discomforts inherent in

participation Obligations of being a subject What happens if leave study

prematurely

What might a subject want to know?

What recompense ($$) for participating?

What consequence if things go wrong? Who pays for what?

Facts about person offering to enroll me might be relevant to determining his/her motivations

Are these all in the standard forms?

Research study/ purposes/benefits: yes

Treatment being tested and randomized alternative: yes

Availability of third alternatives? Sometimes Often doesn’t include option of study

treatment outside research study

Are these all in the standard forms?

Risks/discomforts inherent in study Generally included Tests may be referred to as “routine” This may be understood as “risk-free”

rather than common outside the research protocol

Are these all in the standard forms?

Obligations/effect of leaving prematurely? Usually covered Doesn’t indicate that won’t be told of

interim results

Why might a subject want to know – and a researcher not want to reveal this??

Results show new treatment more efficaciousConfidence interval overlaps null hypothesisCompare researcher interest and patient interest

Are these all in the standard forms?

Risk/benefit of standard and alternative? Yes, but boiler-plate COST study of laparoscopic surgery for

colon cancer Form language: “it is possible that the

new technique may change the way the tumor grows back after surgery if it does”

Vs. Benefits of “smaller incisions and faster recovery”

Are these all in the standard forms?

Financial Issues Payment to P for time/inconvenience? Y Coverage of Medical Costs during trial?

Y Compensation for damages from trial?

Usually not included/not covered Incentives to Researcher/Doctor to

Include P in trial? No

Can we do needed research if we tell the truth and the whole truth?

Can we treat subjects with something like the ethics we use for patients?