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.