Human Subjects in Medical Human Subjects in Medical ResearchResearch

So far we have focused on So far we have focused on individualindividual autonomyautonomy and and individualindividual well-beingwell-being (nonmaleficence and beneficence).(nonmaleficence and beneficence).

Now we will consider how individual Now we will consider how individual autonomy and well-being are autonomy and well-being are balanced against balanced against utilitarianutilitarian considerations.considerations.

We have also emphasized role-related We have also emphasized role-related obligations. In this context, two obligations. In this context, two different roles are relevant.different roles are relevant.Role of Role of therapisttherapist (primary concern is (primary concern is well-being of patients)well-being of patients)Role of Role of researcherresearcher (primary concern is (primary concern is acquisition of knowledge that will help acquisition of knowledge that will help future patients)future patients)

MoralMoral problemsproblems arise when the arise when the obligations a HCP has as a obligations a HCP has as a therapisttherapist conflict with obligations she has as a conflict with obligations she has as a researcherresearcher..

Obligations as a researcher Obligations as a researcher

the growth of knowledge to help the growth of knowledge to help

future pts (utilitarian support)future pts (utilitarian support)

Two types of (moral) problems emerge Two types of (moral) problems emerge with (some) medical research:with (some) medical research:

Some research projects require Some research projects require deceivingdeceiving subjects (contrary to subjects (contrary to autonomy)autonomy)

Some research projects put subjects Some research projects put subjects at at riskrisk (contrary to beneficence and (contrary to beneficence and nonmaleficence)nonmaleficence)

Much research is done on nonhuman Much research is done on nonhuman animals. Questions raised:animals. Questions raised:

Are the animals harmed?Are the animals harmed? Do the benefits outweigh the harms?Do the benefits outweigh the harms? Can the benefits be obtained without Can the benefits be obtained without

the harm?the harm?

Our focus will be on Our focus will be on humanhuman subjects. subjects.

Using Using humanhuman subjects (in addition to subjects (in addition to animals) is animals) is necessarynecessary because (i) because (i) drugs or treatments don’t always drugs or treatments don’t always have the same effects on humans as have the same effects on humans as on animals, and (ii) some medical on animals, and (ii) some medical problems are unique to humans.problems are unique to humans.

Any institution (hospital, university) Any institution (hospital, university) whose members do research on whose members do research on humans and receives federal funds humans and receives federal funds must have an must have an InstitutionalInstitutional ReviewReview BoardBoard (IRB). (IRB).

An IRB is a committee that examines An IRB is a committee that examines research protocols (with humans) for research protocols (with humans) for their ethical acceptability.their ethical acceptability.

The composition of IRBs is multi-The composition of IRBs is multi-disciplinary.disciplinary.

In hospitals: nurses, physicians, In hospitals: nurses, physicians, pharmacists, attorneys, social pharmacists, attorneys, social workers, chaplains, ethicists, etc.workers, chaplains, ethicists, etc.

In universities: persons from the life In universities: persons from the life and social sciences, ethicists, and social sciences, ethicists, community members.community members.

It is common to distinguish between It is common to distinguish between therapeutictherapeutic and and nontherapeuticnontherapeutic research. research. AllAll medical research – medical research – therapeutic and nontherapeutic – therapeutic and nontherapeutic – involves (i) employing unproven involves (i) employing unproven medical interventions and (ii) seeking medical interventions and (ii) seeking to acquire generalizable knowledge.to acquire generalizable knowledge.

In addition to (i) and (ii), In addition to (i) and (ii), therapeutictherapeutic research aims to produce research aims to produce directdirect medicalmedical benefitsbenefits for the subjects for the subjects (pts).(pts).

With With nontherapeuticnontherapeutic research, no research, no direct medical benefits are expected; direct medical benefits are expected; any such benefits are an unexpected any such benefits are an unexpected bonus.bonus.

The first The first codecode ofof ethicsethics for for researchers was devised after the researchers was devised after the Doctors’ Trial at the Nuremberg Doctors’ Trial at the Nuremberg Tribunal (after World War II).Tribunal (after World War II).

Indictments filed against 23 German Indictments filed against 23 German doctors on Oct. 25, 1946.doctors on Oct. 25, 1946.

Trial ended on July 19, 1947. Trial ended on July 19, 1947. SixteenSixteen of the defendants were convicted; of the defendants were convicted; sevenseven received the death penalty. received the death penalty.

Crimes committed under the guise of Crimes committed under the guise of scientific research included:scientific research included:

High-altitude studies (subjects died High-altitude studies (subjects died of oxygen deprivation)of oxygen deprivation)

Hypothermia studies (subjects died Hypothermia studies (subjects died of exposure to cold water)of exposure to cold water)

Drinking seawater until symptoms of Drinking seawater until symptoms of poisoning appeared.poisoning appeared.

Nazi studies cont.Nazi studies cont.

Deliberately infecting persons with Deliberately infecting persons with malaria and treating them with malaria and treating them with experimental drugs.experimental drugs.

Studies on twins (conducted by Josef Studies on twins (conducted by Josef Mengele) where the purpose was to Mengele) where the purpose was to determine whether “nature” or determine whether “nature” or “nurture” was the primary influence “nurture” was the primary influence on _____.on _____.

The “Nuremberg Code” (1948) was The “Nuremberg Code” (1948) was devised to set out ethical devised to set out ethical requirements for research involving requirements for research involving human subjects.human subjects.

Requirement of voluntary consent is Requirement of voluntary consent is absolute.absolute.

Because of this, children may not be Because of this, children may not be used in medical research.used in medical research.

Nuremberg Code cont.Nuremberg Code cont.

Subjects must be informed about the Subjects must be informed about the naturenature and and purposepurpose of the research, of the research, about the about the benefitsbenefits, , risksrisks, and , and durationduration of the research. of the research.

No distinction was made between No distinction was made between therapeutic and nontherapeutic therapeutic and nontherapeutic research.research.

Subsequently the “Nuremberg Code” Subsequently the “Nuremberg Code” has come to be seen as has come to be seen as (understandably) too restrictive.(understandably) too restrictive.

Two later codes: “Declaration of Two later codes: “Declaration of Helsinki” (World Medical Association, Helsinki” (World Medical Association, 1964 + revisions) and “American 1964 + revisions) and “American Medical Association Guidelines …” Medical Association Guidelines …” (1966 + revisions).(1966 + revisions).

These two codes differ from These two codes differ from Nuremberg in two key respects:Nuremberg in two key respects:They distinguish between therapeutic They distinguish between therapeutic and nontherapeutic research (and and nontherapeutic research (and imply more “leeway” with former)imply more “leeway” with former)They allow the use of incompetent They allow the use of incompetent subjects (e.g., children) under certain subjects (e.g., children) under certain conditions.conditions.

Both codes emphasize:Both codes emphasize:Subjects’ consent must be freely given.Subjects’ consent must be freely given.Subjects must be informed (nature, Subjects must be informed (nature, purpose, risks, benefits, duration)purpose, risks, benefits, duration)Subjects must be told they are free to Subjects must be told they are free to withdrawwithdraw at any time. at any time.Sometimes permits use of Sometimes permits use of incompetents.incompetents.

One important difference between One important difference between “Declaration” and “AMA Guidelines” “Declaration” and “AMA Guidelines” for use of children:for use of children:““Declaration” requires only informed Declaration” requires only informed consent of guardian.consent of guardian.““Guidelines” require informed consent Guidelines” require informed consent plusplus research is such that no research is such that no competent subject would be suitable.competent subject would be suitable.

Legacy of the “Nuremberg Code” is Legacy of the “Nuremberg Code” is the requirement of subjects’ the requirement of subjects’ voluntary, informed consent.voluntary, informed consent.

Purpose of consent is to respect Purpose of consent is to respect autonomyautonomy and and protectprotect subjects. subjects.

Regarding children: it is assumed Regarding children: it is assumed that parents will be motivated to that parents will be motivated to protect them from harm.protect them from harm.