B IOMEDICAL RESEARCH METHODS Unit I Chapter 3

C HEMICAL, MECHANICAL, MATHEMATICAL AND COMPUTER SIMULATIONS Prove most useful in the preliminary research stages where scientists can simulate ideas about new research directions Helpful in understanding complicated biological principles and dynamics Provide ideas about new research directions to pursue

C HEMICAL MODELS Analytical chemistry tests detect a substance or measure its potency Useful in developing vaccines, prescription drugs and vitamins

M ATHEMATICAL AND COMPUTER MODELS Can predict biological responses on the basis of a chemical’s structure and “activity” in an organism The biological effects of chemicals can be quantified and correlated with a chemical’s biochemical properties, composition and structure Databases can be compared

M ATHEMATICAL AND COMPUTER MODELS STRENGTHSLIMITATIONS Increase` speed and efficiency in the use of data Cannot replace laboratory testing The simpler the system being modeled tends to lead to more accurate results Do not generate data; only process data that has been entered Able to extrapolate dataRely on existing data May reduce the number of animals required for research Equipment and software is expensive STRENGTHSLIMITATIONS Increase` speed and efficiency in the use of data Cannot replace laboratory testing The simpler the system being modeled tends to lead to more accurate results Do not generate data; only process data that has been entered Able to extrapolate dataRely on existing data May reduce the number of animals required for research Equipment and software is expensive

I N V ITRO STUDIES Means “in glass” Term used for any biological process or reaction that takes place in an artificial environment Cells or tissues being studied originally come from a living organism Cell cultures, isolated tissues and organs are used in early and intermediate stages of biomedical research Potential remedies are first tested in this manner to discover how they interact with cells and tissues

I N V ITRO STUDIES STRENGTHSLIMITATIONS Able to study single effect of a substance in isolation Biochemical process leading from chemical exposure to toxic effect cannot be duplicated in vitro Less expensive, less time consuming, more accurate and more readily controlled than in vivo (whole animal) Cells grown in culture are not exposed to other functions taking place in a living organism Able to control temperature, acidity, oxygen levels, and environmental conditions of cultured cells Cells do not metabolize toxins in culture the same way they do in the whole body Cell cultures often contain cells that can replicate themselves in the laboratory Difficult to maintain differentiated cells in a culture Critical to the study of viruses because viruses can only grow in living cells Cell cultures cannot generate sufficiently reliable data about how a substance affects a complex interactive system

N ON - HUMAN ANIMAL MODELS Animals provide the best known surrogate for humans in the laboratory Vital research model because they provide whole, complex living system that can interact and react to stimuli much as humans do

N ON - HUMAN ANIMAL MODELS STRENGTHSLIMITATIONS Ethical alternative to the use of humans in experimental studies Results from experimental animal studies must be extrapolated to humans Provide whole, integrated biological system and are best surrogate for the complexities of the human system. More variables than a cell or tissue culture Experiments can be designed in which they can control for more variables Research animals are expensive to purchase, house, feed, and provide with veterinary care Governed by extensive, time- consuming and costly system of federal regulations

E XAMPLES OF ANIMAL MODELS Cystic fibrosis Accidents Heart disease Vaccines and infectious diseases AIDS Hepatitis B Anthrax Wound healing Leprosy Diabetes Cancer

I TCHY SLEEP DISEASE ACTIVITY

H UMAN CLINICAL TRIALS The pharmaceutical firm files an Investigational New Drug (IND) application with the Food and Drug Administration (FDA). This application shows the results of laboratory testing and explains how the drug is made Three phases

P HASES FOR HUMAN CLINICAL TRIALS PHASE I TRIALS Researchers determine the drug’s interaction with the human system, including how it is absorbed, distributed, metabolized and excreted, and the likely duration of its therapeutic effect Involves small number of healthy volunteers Takes approximately one year

P HASES FOR HUMAN CLINICAL TRIALS PHASE II TRIALS Uses controlled tests to help determine a drug’s effectiveness Studies involve 100 to 300 volunteer patients Simultaneous animal and human tests are conducted at this stage as researchers continue to assess the safety of the drug Takes approximately two years

P HASES FOR HUMAN CLINICAL TRIALS PHASE III TRIALS Conducted to confirm the results of earlier efficacy tests and further identify any adverse reactions Involves 1000 to 3000 volunteer patients in medical clinics and hospitals Takes approximately three years

H UMAN CLINICAL TRIALS When complete, the pharmaceutical firm files a New Drug Application (NDA) with the FDA. Takes approximately 2 ½ years to complete Comprehensive statement of the information on: Drug structure Scientific rationale Purpose of the drug therapy Pre-clinical animal and lab study results All human clinical testing results Drug formulation Production details Company’s proposed labeling

THE WHOLE PROCESS Takes approximately 12 years from initiation of animal and other laboratory studies through all phases of clinical trials and submission of data to the FDA for approval For each new medicine approved, the cost is hundreds of millions of dollars.

THE WHOLE PROCESS FDA ApprovalFDA Review Clinical Studies Phase III: Extensive clinical testing Clinical Studies Phase II: Effectiveness Clinical Studies Phase I: Safety studies Laboratory and Animal Studies

H UMAN C LINICAL T RIALS STRENGTHSLIMITATIONS Provides actual human data on efficiency and safety of promising new drugs Ethical and moral considerations with the extent human volunteers can be used as test subjects Requires extensive pre-clinical testing before it can be conducted Numerous variables which may affect the test data are introduced whenever humans are used as test subjects

HUMAN CLINICAL STUDIES ACTIVITY

EPIDEMIOLOGICAL STUDIES The study of disease incidence and its distribution in a population Divided into three general types Experimental: the human equivalent to of animal testing Descriptive : analyzes data on the distribution and extent of health problems or other conditions in various populations, trying to find correlations among characteristics. Observational : uses data derived from individuals or small groups. Data evaluated statistically to determine the strengths of association between a particular variable and disease

EPIDEMIOLOGICAL STUDIES Cohort studies: Well-characterized and homogenous group is studied over time Case-controlled studies: a control group is selected retrospectively based on variables thought to be relevant to the effort

EXAMPLES OF EPIDEMIOLOGICAL STUDIES

CLASSROOM EPIDEMIC ACTIVITY

ACTIVITY You are the epidemiologist and are to use the scientific method to track the contaminated source

ACTIVITY You are a biomedical researcher and will investigate a mysterious disease

ACTIVITY What types of tests would be required to asses the safety and effectiveness of various products?