EVALUATION OF THE COIN SIGN AS A DIAGNOSTIC TEST OF PLEURAL EFFUSION

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EVALUATION OF THE COIN SIGN AS A DIAGNOSTIC TEST OF PLEURAL EFFUSION Powered By Docstoc
					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

    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   actions   on
unaccepted behaviors.
           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


    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 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. 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.

				
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