BIOMEDICAL RESEARCH METHODS

Unit I

Chapter 3

CHEMICAL, 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

CHEMICAL MODELS

Analytical chemistry tests detect a substance or measure its potency

Useful in developing vaccines, prescription drugs and vitamins

MATHEMATICAL 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

MATHEMATICAL AND COMPUTER MODELS

STRENGTHS LIMITATIONS

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 data Rely on existing data

May reduce the number of animals required for research

Equipment and software is expensive

STRENGTHS LIMITATIONS

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 data Rely on existing data

May reduce the number of animals required for research

Equipment and software is expensive

IN VITRO 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

IN VITRO STUDIESSTRENGTHS LIMITATIONS

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

NON-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

NON-HUMAN ANIMAL MODELSSTRENGTHS LIMITATIONS

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

EXAMPLES OF ANIMAL MODELS

Cystic fibrosis Accidents Heart disease Vaccines and infectious diseases AIDS Hepatitis B Anthrax Wound healing Leprosy Diabetes Cancer

ITCHY SLEEP DISEASE ACTIVITY

HUMAN 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

PHASES 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

PHASES 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

PHASES 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

HUMAN 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 Approval

FDA Review

Clinical Studies Phase III:Extensive clinical testing

Clinical Studies Phase II:Effectiveness

Clinical Studies Phase I:Safety studies

Laboratory and Animal Studies

HUMAN CLINICAL TRIALS

STRENGTHS LIMITATIONS

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 STUDIESACTIVITY

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 assess the

safety and effectiveness of various products?