Ética en Investigación Internacional


History, policy and consent: Ethics in Human Subjects Research


Keneth Goodman, M.D., Universidad de Miami, EE.UU.


Key historical antecedents


1932-1972 — Tuskegee syphilis study (U.S.)

1940-1945 — Nazi physicians’ experiments (Germany)

1940s-1970s — Human radiation experiments (U.S.)



Results: Focus on consent


1949 — Nuremberg Code


1964 et seq. — World Health Organization’s Declaration of Helsinki (http://www.wma.net/e/policy/17-c_e.html)


1978 — U.S.  Belmont Report


1983-1998 — U.S. 45CFR46 (Title 45 [Public Welfare] Code of Federal Regulations Part 46 [Protection of Human Subjects])


1993, 2002 – International Ethical Guidelines for Biomedical Research Involving Human Subjects, Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization.



Components of valid consent


1.      Adequate information


q                   Risks

q                   Benefits

q                   Alternatives

q                   Investigator incentives


2.      Absence of coercion


q                   No threats, pressure, “spin”

q                   Refusal must not affect care

q                   Incentives, payment as potential corrupters


3.      Capacity/competence


q                   Competence not a binary value

q                   Subjects may lack capacity for some things, not others

q                   Special challenges for children, psychiatric patients, others


Special issues


q           Therapeutic misconception (belief by subjects that merely participating in a study will have a beneficial effect)

q           Vulnerable populations (Children? Women? Minorities? Poor people? Drug abusers? Etc.)

q           Patient-subject tension (can a physician carry out fiduciary duties to patients and at the same time encourage them to participate in studies from which they may derive no benefit?)

q           Genetics, banked tissue/sera research

q           Database research, chart reviews, etc.

q           Public health; health services

q           Use of placebos

q           Secondary use of data

q           Data sharing and data as intellectual property 


Practical Strategies for Irb/Rec Review

(Institutional Review Board/Research Ethics Committee)


1. Valid consent (see above)


2. Confidentiality and privacy


q           “Public disclosure of private facts” v. “intrusion upon seclusion”

q           International value, but with some cultural variation

q           ‘X’ exceptionalism (HIV, STD, DNA, DSM) – i.e., the idea that some maladies or data are more stigmatizing or lead to more discrimination than others … and hence should elicit greater protections.

q           More an issue in countries without adequate health insurance


3. Conflicts of interest


q           Pharmaceutical sponsorship

q           Publication and authorship

q           Intellectual property




Special issues in International Research


 Differences in consent custom (group consent vs. individual consent)

Use of placebos

Variable roles, status for women

North-South exploitation

“Bleed and flee studies” (wherein investigators use a native population as a source of blood or other potentially valuable biological material without compensation or return)

Heightened risk of therapeutic misconception

Duty to study maladies of importance to study population



Practical solutions


Selected recommendations,  (U.S.) National Bioethics Advisory Commission. Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries, 2001 (http://www.georgetown.edu/research/nrcbl/nbac/pubs.html):


1. The U.S. government should not sponsor or conduct clinical trials that do not, at a minimum, provide the following ethical protections:


a) prior review of research by an ethics review committee(s)

b) minimization of risk to research participants;

c) risks of harm that are reasonable in relation to potential benefits;

d) adequate care of and compensation to participants for injuries directly sustained during   


e) individual informed consent from all competent adult participants in research;

f) equal regard for all participants; and

g) equitable distribution of the burdens and benefits of research.


2. Clinical trials conducted in developing countries should be limited to those studies that are responsive to the health needs of the host country.


3. Researchers and sponsors should design clinical trials that provide members of any control group with an established effective treatment, whether or not such treatment is available in the host country. Any study that would not provide the control group with an established effective treatment should include a justification for using an alternative design. Ethics review committees must assess the justification provided, including the risks to participants, and the overall ethical acceptability of the research design.