THE MODELING OF SCIENCE.
Factors that influence Science.
Onofre Morán MD, MSc.
Professor, Faculty of Medicine,
Universidad Autónoma de San Luis
Potosí, S.L.P. México.
PhD Candidate
University of British Columbia,
Vancouver, Canada.
FACTORS THAT “MODEL” THE
MEDICAL SCIENCES
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Personal knowledge.
Bioethics.
Government: Funding, Regulations.
Industry.
The media.
Culture.
Expert panels.
Patients.
Journal editors, etc.
PERSONAL KNOWLEDGE
A researcher can successfully develop a
research on phenomena that are related to his
main knowledge or capabilities.
This imposes a limitation in the field were the
researcher will work and the kind of questions
a researcher can answer within that field.
PERSONAL KNOWLEDGE
While the collection of data of the surrounding
world depends in a great deal on the
physiological integrity of our senses, another
very important part is the inner state of our
minds, which will itself depend on our cultural
upbringing,
our
knowledge
and
our
expectations, and will not be determined only by
the physical properties of the surrounding
objects.
(Chalmers, A.F. What is this thing called Science? 1999).
PERSONAL KNOWLEDGE
Furthermore,
the
relevance
and
interpretation of experimental results
depend on the theoretical context,
which in turn is influenced by previous
knowledge.
.
(Chalmers, A.F. What is this thing called Science? 1999)
PERSONAL KNOWLEDGE
Scientific method:
The principles and procedures used in the
systematic
pursuit
of
intersubjectively
accessible knowledge and involving as
necessary conditions the recognition and
formulation of a problem, the collection of data
through observation and if possible experiment,
and the testing and the confirmation of the
hypotheses formulated”.
(Webster’s Third New International Dictionary. 1986)
PERSONAL KNOWLEDGE
Even researchers within the same field will have
a different view of the scientific process and a
different approach for the resolutions of the
same problems.
This way, some researchers may prefer the
falsificationist approach proposed by Popper,
while others the verificationist approach
proposed by inductivists.
(Rothman KJ. Causal Inference, 1988)
PERSONAL KNOWLEDGE
“Half of what you are taught as medical students will in
10 years have been shown to be wrong. And the
trouble is, none of your teachers knows which half ”.
(Dr. Sydney Burwell, Dean of Harvard Medical School, 1956)
Currently, with the application of the scientific method,
under the Evidence Medicine approach, over 90% of
the studies published 5 years before, are still relevant.
(ACP J Club. 1997 Jan-Feb;126(1):A16 )
PERSONAL KNOWLEDGE
In conclusion, personal knowledge, mainly of the proper
knowledge required for scientific purposes, as well as
personal experience, have a modeling effect in the
entire scientific process; from the researcher’s
perception of the phenomena and the approach used
to study those phenomena, to the inferences drawn
from the results.
BIOETHICS
BIOETHICS
Since the Nuremberg Code in 1946, it was established
that whatever the benefits potentially gained from the
use of human beings as experimental subjects, there
cannot be any justification for treating people as mere
means to an end.
That the rights of the individual should remain
paramount, and no scientific advance can outweigh
the harm done by unethical research.
BIOETHICS
RECCOMENDATIONS
The Declaration of Helsinki in 1964. (World Medical Association )
The Belmont Report in 1979.
(The National Commission for the Protection of Human Subjects of Research)
The International Conference on Harmonization Good
Clinical Practice guideline in 1989. (USA, Japan, Europe)
The International Ethical Guidelines for Biomedical
Research Involving Human Subjects in 1993.
(Council for International Organization of medical Sciences & WHO)
BIOETHICS
FOUNDATIONS
Non-maleficence/beneficence: Intends to assure
that no harm will be done to the research subjects
(primum non nocere).
Autonomy: It recognizes that a person has the
power to decide and act in her own best interest.
Justice: It intends to prevent an unfair
discrimination against any person who wishes to
participate in the research (providing they fulfill the
selection criteria of course).
BIOETHICS
Non-maleficence/beneficence
A research proposal cannot be ethical if it lacks
scientific validity; poorly designed research entails
putting the subjects at risk or, at least, to some
inconvenience, for no clear benefit.
This means that every research proposal should
have a clear hypothesis stated and that hypothesis
should be relevant to the medical knowledge and of
potential benefit to society.
The hypothesis should be properly answered by the
design of the study and the methods should be
appropriate, in order to provide a valid scientific
answer.
BIOETHICS
Non-maleficence/beneficence
In therapeutic research, if one of the treatments
could cause harm, then the research should never
begin.
On the other hand, one cannot justify withholding a
treatment of known benefit to patients, merely in the
interest of research.
BIOETHICS
Non-maleficence/beneficence
To ensure scientific validity, besides a randomized
allocation to the treatments under comparison, the
researchers and subjects under study should be
blinded; therefore it is obvious that therapeutic trials
involve some element of risk to the subjects.
A research of this kind is acceptable only when the
safety of subjects throughout the study period is
assured.
Specific monitoring procedures and safety measures
should be clearly stated in the research protocol.
BIOETHICS
Autonomy
In all types of research, the provision
of comprehensive and accurate
information to the subjects, or the
proxy decision-makers, through the
informed consent, is crucial.
Without
such
information,
the
consent granted will not be valid.
BIOETHICS
Autonomy
Giving informed consent is not to be
confused with the signing of a consent
form.
To achieve the fully valid consent, great
attention must be paid to the quality of the
communication about the research project.
All explanations must be in non-technical
and easily understandable language.
BIOETHICS
Autonomy
The information provided in the informed consent
format, should include a clear description of the
aims, methods, anticipated benefits and potential
hazards of the study and the discomfort it may
entail.
He or she should be informed that they have the
liberty to abstain from participation in the study
and that refusal to participate will in no way alter
the medical care the subject is receiving.
BIOETHICS
In conclusion, there are many factors, introduced by
Bioethics, that should be considered in the
planning and execution of a research project
involving human subjects.
All these factors have changed in a great deal the
way Medical research has been carried out in the
last few decades and they likely will continue
changing it in the future.
GOVERNMENT
GOVERNMENT
Funding
By defining the characteristics a
research project should have to be
funded.
Regulations
By
imposing
legal
unaccepted behaviors.
actions
on
GOVERNMENT
BUDGET
NIH: > $5.8 billion for clinical research only.
(NIH Grants Policy Statement. Mar, 2001)
CIHR: $230 million in 2000-2001.
(Canadian Institutes of Health Research, 2001)
CONACYT: $ 2 million in 2000-2001.
(SEP-CONACYT. Apoyos a la Investigación Científica. México, 2000.)
GOVERNMENT
NIH grant policy
 Human Subjects. Confidentiality.
 Education in the Protection of Human Research Participants.
 Data and Safety Monitoring.
 Investigation of New Drugs.
 Measuring system.
 Inclusion of Women, Children, and Minorities in Clinical Research.
 Age Discrimination.
 Civil Rights.
 Sex Discrimination.
 Handicapped Individuals.
 Biosafety in Microbiological and Biomedical Laboratories.
 Use of Laboratory animals.
 Availability of Research Results: Publications, Intellectual Property.
 Rights, and Sharing Biomedical Research Resources.
 Types of new Research that will and will NOT be funded.
GOVERNMENT
NIH grant policy
 A grantee may not conduct research involving
human subjects or expend Federal funds for
research involving human subjects, unless it has
an Office for Human Research Protections
(OHRP)-approved assurance of compliance with
the requirements of 45 Code of Federal
Regulations (CFR) and the research has been
approved by an Institutional Review Board (IRB).
GOVERNMENT
NIH grant policy
 Require that women and members of
minority groups and their subpopulations be
included in any NIH-supported research
project involving human subjects, unless a
clear and compelling rationale and
justification establishes that inclusion is
inappropriate with respect to the health of
the subjects, the purpose of the research,
or other circumstances.
GOVERNMENT
NIH grant policy
Grantees are responsible for meeting Federal, State,
and local health and safety standards, such:
-Biosafety in Microbiological and Biomedical Laboratories , U.S.
Department of Health and Human Services, Centers for Disease
Control and Prevention, and the National Institutes of Health. HHS
Publication No. (CDC) 93-8395. 29 CFR 1910.1030
-Bloodborne Pathogens; 29 CFR 1910.1450.
-Occupational Exposure to Hazardous Chemicals in Laboratories;
Prudent Practices for Safety in Laboratories (1995), National
Research Council; 42 CFR Part 72
- Interstate Shipment of Etiological Agents; Procedures for Domestic
Handling and Transport of Diagnostic Specimens and Etiologic
Agents, 1994 (3rd ed.)
-National Committee for Clinical Laboratory Standards.
-Nuclear Regulatory Commission Standards and Regulations, pursuant
to the Energy Reorganization Act of 1974.
GOVERNMENT
NIH regulatory requirements
Regulations are codified at Title 45, Part 46 of the
Code of Federal Regulations, Protection of Human
Subjects.
(Code of Federal Regulations. Chapter VI--National Science Foundation Title 45-Public Welfare, Volume 3, Parts 500 to 1199. October 1, 2000. )
GOVERNMENT
Regulations
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Informed Consent
Institutional Review Boards
Confidentiality
Misconduct in Science
GOVERNMENT
Regulations
INFORMED CONSENT:
No investigator may involve a human being as
a subject in research, unless the investigator
has obtained the legally effective informed
consent of the subject or the subject's legally
authorized representative.
GOVERNMENT
Regulations
INFORMED CONSENT:
An IRB may waive the requirement if it finds that either:
a) That the only record linking the subject and the
research would be the consent document and the
principal risk would be potential harm resulting from a
breach of confidentiality; or
b) That the research presents no more than minimal risk
of harm to subjects and involves no procedures for which
written consent is normally required outside of the
research context.
In cases in which the documentation requirement is
waived, the IRB may require the investigator to provide
subjects with a written statement regarding the research.
GOVERNMENT
Regulations
Criteria for IRB approval of research:
(1) Risks to subjects are minimized:
By using
procedures which are consistent with sound research
design.
(2) Risks to subjects are reasonable in relation to
anticipated benefits,
(3) Selection of subjects is equitable.
(4) Informed consent appropriately documented.
(5) The research plan makes adequate provision to
ensure the safety of subjects.
(6) There are adequate provisions to protect the privacy
of subjects and to maintain the confidentiality of data.
GOVERNMENT
Regulations
Misconduct:
Misconduct
means
fabrication,
falsification,
plagiarism, or other serious deviation from accepted
practices in proposing, carrying out, or reporting
results.
Actions:
Could range from sending a letter of reprimand to the
individual, to immediately suspend an active award
and debar or suspend an individual, department, or
institution from participation in NSF programs for a
specified period. They are not exhaustive and do not
include possible criminal sanctions.
(Title 45 of the CFR, in Sec. 689.1)
GOVERNMENT
FDA LIST OF RESEARCHERS WITH SCIENTIFIC MISCONDUCT
(examples):
ANGELIDES, KIMON J (ORI ADMINISTRATIVE ACTION) INSTITUTION THAT
LED INVESTIGATION: BAYLOR COLLEGE OF MEDICINE CITY/STATE:
HOUSTON
TX
SANCTIONED
AGAINST/ACTION
REQUIRED:
APPLYING/RECEIVING FEDERAL GRANTS, CONTRACTS OR LOANS: Y
EFFECTIVE DATE: 02/22/1999 EXPIRATION DATE: 02/21/2004 SERVING ON
COMMITTEE: Y EFFECTIVE DATE: 02/22/1999 EXPIRATION DATE:
02/21/2004 CORRECTION/RETRACTION AGREEMENT: Y EFFECTIVE DATE:
02/22/1999 EXPIRATION DATE: 03/24/1999 NARRATIVE: WITHIN 30 DAYS OF
2/22/99, DR. ANGELIDES IS REQUIRED TO SUBMIT A LETTER TO THE
EDITORS OF PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON,
ANNALS OF THE NEW YORK ACADEMY OF SCIENCE, GLIA, AND
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCE REQUESTING
RETRACTION OF THE FALSIFIED FIGURES AND TEXT IN THE FOUR
SCIENTIFIC PAPERS. PROC. R. SOC. LONDON 238:39-51, 1989, ANN. N.Y.
ACAD. SCI. 633:255-271, 1991, GLIA 2:353-369, 1989, PROC. NATL. ACAD.
SCI. (USA) 87:9290-9294, 1990.
GOVERNMENT
FDA LIST OF RESEARCHERS WITH SCIENTIFIC
MISCONDUCT (examples):
DREYER, EVAN B (ORI ADMINISTRATIVE ACTION) INSTITUTION
THAT LED INVESTIGATION: HARVARD MEDICAL SCHOOL
CITY/STATE: BOSTON MA SANCTIONED AGAINST/ACTION
REQUIRED:
APPLYING/RECEIVING
FEDERAL
GRANTS,
CONTRACTS OR LOANS:
EFFECTIVE DATE: 11/15/2000
EXPIRATION DATE: 11/14/2010. SERVING ON COMMITTEE: Y
EFFECTIVE DATE: 11/15/2000 EXPIRATION DATE: 11/14/2010
VOLUNTARY EXCLUSION: Y EFFECTIVE DATE: 11/15/2000
EXPIRATION
DATE:
11/14/2010
NARRATIVE:
VOLUNTARY
EXCLUSION AGREEMENT INCLUDES PROVISION THAT SUBJECT
WILL EXCLUDE HIMSELF FROM SERVING AS A MENTOR TO ANY
GRADUATE STUDENT, FELLOW, OR OTHER INDIVIDUAL WHO
APPLIES FOR OR RECEIVES FEDERAL FUNDING.
GOVERNMENT
In conclusion, there are currently many
economical and regulatory factors, usually
linked with bioethical aspects, influencing the
research performed in the Health Sciences.
In the USA they are structured very efficiently in
the most important institutions that legislate and
fund health research at the national level.
Furthermore, researchers who do not comply
with
these
regulations
receive
moral,
professional and even criminal sanctions by the
corresponding government institutions.
INDUSTRY
INDUSTRY
- Biotechnology Industry
- Pharmaceutical Industry
- Tobacco Industry
INDUSTRY
Biotechnology Industry
Serologic Diagnostic Tools:
Many instruments are now indispensable for the valid
measurement of substances in the serum and other
body fluids in clinical and toxicological research:
Automated Blood Cell Counters.
Electrophoretic methods.
Nephelometry.
Polymerase chain reaction.
Mass spectrometry, etc.
INDUSTRY
Biotechnology Industry
Image Diagnostic Studies:
Similarly, no valid research can be carried out in
our time without the use of sensitive
technologies that allow the detection of
anatomic abnormalities:
Computerized Tomography.
Magnetic Resonance Imaging.
Nuclear Medicine studies.
Digital Substraction Angiography, etc.
INDUSTRY
Biotechnology Industry
Endoscopic studies:
Currently it would be considered unethical to
conduct many clinical research studies
without the use of Endoscopic procedures
(biopsies, brushings, washings, etc).
INDUSTRY
Pharmaceutical Industry
Multinational, randomized clinical trials of vaccines and
therapeutic drugs that have been supported by the
Pharmaceutical industry:
-The Scandinavian Simvastatin Survival Study:
5
European countries; 4,444 patients; 5 y.
(Lancet. 1994 Nov 19;344(8934):1383-9. Merck Research Laboratories)
- The LIPID study:
>9,000 patients; 250 clinicians; 6 yr.
(N Engl J Med. 1998 Nov 5;339(19):1349-57. Bristol-Myers Squibb Co.)
INDUSTRY
Pharmaceutical Industry
Potential Problems:
a) Increased drug prices.
b) The relationship between industry and
investigators or universities has been
strengthened and has become increasingly
complex, creating a variety of situations which
have the potential of leading to ethical
compromises.
INDUSTRY
Tobacco Industry
The tobacco industry has been an influence on Science,
and policies implemented based on scientific results.
By using the industry's size, wealth, and legal
resources to intimidate individuals and local
governmental bodies; spending large sums of money to
frame the public debate about smoking regulations
around 'rights and liberty' rather than health, and
portraying its tobacco company adversaries as
extremists; 'investing' thousands of dollars in campaign
contributions to politicians; and using financial
resources to influence science.
(Br Med Bull. 1996 Jan;52(1):183-92)
INDUSTRY
In conclusion, the Industry may influence the
scientific process from the feasibility of a
study, to the procedural aspects, including
ethical issues associated to economical
interests.
THE MEDIA
THE MEDIA
The media has an effect on the Medical Sciences
through
the
increase
awareness
and
modification of the public behavior.
Epidemiology is a Science especially prone to
suffer from the media influence, because it
deals with cause-effect relationships and Public
Health issues, which are very commonly
exploited by the media.
THE MEDIA
POTENTIAL INFLUENCES
Feasibility
Selection Bias
Information Bias
Results (Scientific Credibility)
THE MEDIA
Feasibility
The widespread adoption of measures
by the general public can cause
problems in the feasibility of a study.
THE MEDIA
Selection bias
The media may play a role in the health
consciousness of the public.
Volunteerism to participate in a research study is likely to be
associated with age, sex, socioeconomic status and other correlates
of health consciousness that may significantly influence subsequent
morbidity and mortality.
(J Chronic Dis. 1976;29:331-9)
Direct influence when research participants are
invited to participate through the media.
Those willing to participate in clinical trials tend to experience lower
morbidity and mortality than those who do not.
THE MEDIA
Information bias
In (MRFIT) after 7 years of follow-up, there was a nonsignificant 7% decrease in deaths from CHD in the
special intervention group, compared with those
allocated to usual medical care. One factor that
contributed to the inability of the study to detect a
significant difference, despite of the important reductions
on the levels of the 3 risk factors in the special
intervention group, was that a large proportion in the
usual care group also stopped smoking, received and/or
complied with anti-hypertensive medication, and lowered
their blood cholesterol through weight loss or dietary
changes. (J.A.M.A. 1982;248:1465-77)
An undetermined, but likely important component of these
behavior modifications can be attributed to the media
THE MEDIA
Results (Scientific Credibility)
Millions of dollars are being awarded by injuries and a
major company has been forced into bankruptcy
because of litigation over silicone breast implants. Yet
scientific research hasn't established a link between
the implants and disease.
Marcia Angell, executive editor of the New England
Journal of Medicine, blames the tort system, junk
science, and the gullibility of the news media.
She worries that it's now become politically correct to
bash the scientific method in the name of diversity,
multiculturalism, and feminism.
(Med Econ. 1996 Sep 9;73(17):131-3, 136, 139-40)
THE MEDIA
In conclusion, the media may be responsible of
providing information that may be inaccurate
and therefore create confusion in the public;
furthermore, the media can induce the believe
that “evidence” from anecdotic cases have the
same, or even more weight than the scientific
evidence, neglecting the reality of the
multifactorial complexity involved in scientific
research.
CULTURE
CULTURE
Like other sciences, Epidemiology is not “value free” but
colored by and reflective of cultures, customs and
traditions in the place where it is practiced.
A well-conducted Epidemiological study should be directed
towards the improvement in the health of a community,
and in order to achieve this, researchers have to
consider the cultural values and traditions of the
specific community under study.
Not knowing those values and traditions may lead to an
invalid study because the data provided by the
members of the population could be distorted.
Not knowing and understanding the cultural factors of a
community may even make a study impossible.
Conclusions
Conclusions
Many factors influence and model the scientific
process in the Health Sciences: Its objectives,
methods and analysis.
Being aware of them improves our understanding of
research, as an activity subject to the complexity
of human strengths and weaknesses.