THE MODELING OF SCIENCE. Factors that influence Science.

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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.
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FACTORS THAT MODEL THE MEDICAL SCIENCES

•        Personal knowledge.
•         Bioethics.
•         Government Funding, Regulations.
•         Industry.
•         The media.
•         Culture.
•         Expert panels.
•         Patients.
•         Journal editors, etc.

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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.

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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).

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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).

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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.
• (Websters Third New International
  Dictionary. 1986)

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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)

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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-Feb126(1)A16 )

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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 researchers perception of the phenomena
  and the approach used to study those phenomena,
  to the inferences drawn from the results.

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BIOETHICS
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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.

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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)

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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).

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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GOVERNMENT
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GOVERNMENT

• Funding
• By defining the characteristics a research
  project should have to be funded.
• Regulations
• By imposing legal actions on unaccepted
  behaviors.

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GOVERNMENT

• BUDGET
• NIH gt 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.)

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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.

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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).

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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.

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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.

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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. )

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GOVERNMENT

• Regulations
•         Informed Consent
•         Institutional Review Boards
•         Confidentiality
•         Misconduct in Science

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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.

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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.

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GOVERNMENT

• Regulations
• Criteria for IRB approval of research
• Risks to subjects are minimized By using
  procedures which are consistent with sound
  research design.
• Risks to subjects are reasonable in relation to
  anticipated benefits,
• Selection of subjects is equitable.
• Informed consent appropriately documented.
• The research plan makes adequate provision to
  ensure the safety of subjects.
• There are adequate provisions to protect the
  privacy of subjects and to maintain the
  confidentiality of data.

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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)

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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 23839-51, 1989,
  ANN. N.Y. ACAD. SCI. 633255-271, 1991, GLIA
  2353-369, 1989, PROC. NATL. ACAD. SCI. (USA)
  879290-9294, 1990.

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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.

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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.

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INDUSTRY
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INDUSTRY

• - Biotechnology Industry
• - Pharmaceutical Industry
• - Tobacco Industry

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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.

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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.

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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).

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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 19344(8934)1383-9. Merck
  Research Laboratories)
• - The LIPID study
• gt9,000 patients 250 clinicians 6 yr.
• (N Engl J Med. 1998 Nov 5339(19)1349-57.
  Bristol-Myers Squibb Co.)

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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.

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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 Jan52(1)183-92)

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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.

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THE MEDIA
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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.

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THE MEDIA

• POTENTIAL INFLUENCES
• Feasibility
• Selection Bias
• Information Bias
• Results (Scientific Credibility)

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THE MEDIA

• Feasibility
• The widespread adoption of measures
• by the general public can cause problems in the
  feasibility of a study.

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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. 197629331-9)
• 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.

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THE MEDIA

• Information bias
• In (MRFIT) after 7 years of follow-up, there was
  a non-significant 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. 19822481465-77)
• An undetermined, but likely important component
  of these behavior modifications can be attributed
  to the media

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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 973(17)131-3, 136,
  139-40)

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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.

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CULTURE
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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.

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Conclusions
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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.