Approaches and Methods in Pharmacology and Toxicology Research

Question 1

While ___________ ________ is concerned with characterization and/or quantification of patterns in nature, ___________ _________ is concerned with a CAUSAL hypothesis advanced to explain one or more patterns uncovered by descriptive science.

Answer 1

Descriptive science; hypothesis testing

Descriptive: people who smoke get cancer
Hypothesis: why does smoking cause cancer?

Question 2

What is the main issue covered in descriptive science?

Answer 2

a) What are the important observed patterns?
b) Are they more imagined than real?

Question 3

What is the main issue covered in hypothesis testing?

Answer 3

How likely is it that the hypothesis in question is true?

Question 4

A _______ _________ makes a prediction about what you should see under the conditions of the study; the study asks whether this prediction is seen.

Answer 4

Causal hypothesis

Question 5

What is the difference between a hypothesis and a prediction?

Answer 5

A hypothesis: a causal explanation for a given phenomenon/observation/pattern

A prediction: a rigorous, often quantitative, statement, of what will be observed under specific conditions if the hypothesis is true.

If H, then P.

Hypothesis: Consuming greasy high-fat content foods causes more skin oils and breakouts.

Prediction: If the individual consumes greasy foods, then the person will have more skin oils and breakouts.

Question 6

Descriptive science has an ________ instead of a ________.

Answer 6

Objective; hypothesis

Objective: what do you want to measure/evaluate?
Hypothesis: what’s your best guess?

Question 7

What is epidemiology?

Answer 7

The scientific study of the patterns, causes, and effects of health and disease conditions in defined populations.

It is the cornerstone of public health. It identifies risk factors for disease and targets for preventive healthcare. It informs policy decisions and evidence-based practice.

It is central to both pharmacology and toxicology.

Question 8

What are the two types of epidemiological studies?

Answer 8

1) Non-experimental observational studies
2) Experimental/interventional studies

Question 9

(T/F) Observational studies can be population and individual based. They include lots of opinions and trends but lack a hypothesis.

Answer 9

True!

Question 10

What are the three different types of observational studies (individual based - analytic)?

Briefly describe each.

Answer 10

1) Cross-sectional study: determine PREVALENCE.

2) Case-control study: compare groups RETROSPECTIVELY to study the DISEASE. they seek to identify possible predictors of outcomes. Eg., they take a group of people with cancer and without and ask about their lives.

3) Cohort study: study the RISK FACTOR (PROSPECTIVE). they measure events in chronological order and can use to distinguish between cause and effect.

Question 11

What are the two different types of experimental/intervention studies?

Briefly describe each.

Answer 11

1) Randomized Control Trial (RCT): subjects in a population are randomly allocated to different groups (placebo or drug); the results are compared.

2) Non-randomized (Quasi-experimental): subjects in a population are non-randomly allocated to different groups; study population are chosen.

Question 12

What are the advantages and disadvantages of cross-sectional surveys?

Answer 12

Advantages: Quick, can cover whole population, giving representative information whether people are seeking care or not.

Disadvantages: Based mainly on self report (BIAS?); diagnostic information usually inaccurate; can’t establish causal sequence

Question 13

What are the advantages and disadvantages of cohort studies?

Answer 13

Advantages: Prospective so it can establish a CAUSAL sequence; can estimate INCIDENCE.

Disadvantages: Time-consuming; costly

Question 14

What are the advantages and disadvantages of case-control studies?

Answer 14

Advantages: Relatively CHEAP way of focusing on causal factors; stronger than a survey.

Disadvantages: Requires recall of past events (INACCURACY?); controls not equivalent to cases

Question 15

Which observational study is the strongest? Which one is the weakest?

Answer 15

Strongest: COHORT

Weakest: cross-sectional surveys

Question 16

What are the advantages and disadvantages of Randomized Control Trial (RCT)?

Answer 16

Advantages: controls for all main forms of bias; good for both etiological and evaluative research

Disadvantages: ethical concerns in etiological applications; often uses selected populations: issue of GENERALIZABILITY?

Question 17

What are the advantages and disadvantages of Quasi-experiments?

Answer 17

Advantages: May be more practical than RCT: can use “natural experiments”

Disadvantages: Allocation bias often significant

Question 18

(T/F) Case control studies and cohort studies both prove causation.

Answer 18

False! Only cohort (prospective) can prove causation. Case control studies (retrospective) prove correlation.

Question 19

What are the four phases of new drug clinical trials?

Answer 19

Phase 1: Checking for safety; first testing in humans (20-100 volunteers)

Phase 2: Checking for efficacy; how well does the drug work? (100-500 patients)

Phase 3: Confirm results; drug MUST be safe + there’s a comparison with current treatment. (1000-5000 patients)

Phase 4: FDA review/phase 4 trials; safety surveillance in real life patients

Question 20

(T/F) In phase I of cancer treatments, the drug is typically given to cancer patients who’s medications are not working.

Answer 20

True! Healthy volunteers are not used.

Question 21

How does a parallel clinical trial differ than crossover?

Answer 21

Parallel: RTC - two groups are studied; one gets placebo, the other gets drug.

Crossover: each individual takes both placebo + drug and the results are compared.

Question 22

In vitro research models involve biochemical experiments and cell-based experiments.

In vivo research models involve rodent models, comparative models and human models.

Which one has the least level of control vs most level of control?

Which one has increasing level of complexity but also increasing weight of evidence?

Answer 22

Least level of control; vivo
Most level of control; vitro

Increasing level of complexity but also increasing weight of evidence; vivo

Question 23

In vitro (biochem/biophysical) has _______ variability while in vitro (cellular) has ______ variability.

Answer 23

Low; moderate

Question 24

In vivo model is ____ controlled with ______ complexity and _____ variability. It investigates mechanisms and effects at the _________ level.

Answer 24

less; higher; more

physiological

Question 25

(T/F) Mathematical modeling approach leads to a PREDICTED biological effect, while a biological approach leads to a MEASURED biological effect.

Answer 25

True!

Question 26

(T/F) In risk assessment of toxicology, field exposure has increasing ecological relevance and number of influencing factors while laboratory exposure loses relevance.

Answer 26

True!

Question 27

Risk assessment framework involves:

Answer 27

1) Hazard identification (how much is out there, where is it, is it bioaccessible, determine dose, etc)

2) Effect / Exposure assessment (what is the effect?)

3) Risk characterization (how high is the risk?)

4) Risk management