Drug and Genes Lecture 4

Stages of Drug Discovery and Development

1. Target Identification

2. Hit Identification

3. Lead Optimization

4. Pre-Clinical Trials

5. Clinical Trials

6. Drug Approval

Phases of Clinical Trials

1. Phase I: Evaluate safety, safe dosages, side effects (10s, 70%)

2. Phase II: Test effectiveness (100s, 33% to next phase)

3. Phase III: Larger scale safety and effectiveness (1000s, 25-30%)

4. Phase IV: Provide additional info after approval

Drug Development Stages

1. Target Discovery

2. Preclinical

3. Phase I

4. Phase II

5. Phase III

6. FDA Approval and Phase IV

7. Commercial

Discovery to FDA

1. Drug Discovery

2. Preclinical

3. Clinical

4. FDA Preview

5. FDA Approve

Natural to Synthetic Derivatives

- Modify to enhance potency or selectivity

- Improve absorption, longer half-life, reduced toxicity

- Greater control over chemical structure

- Consistent quality and supply

Research Merit and Integrity

Trials should be initiated only when preclinical studies support a well-grounded hypothesis

Respect for Persons

Patients should be treated as independent persons who are capable of making decisions in their own interests

Beneficence

Duty to protect research subjects from harm

Justice

Requires that the selection of research subjects be fair

Confidentiality

Any identifying information is not made available to anyone but the program coordinator

Anonymity

Stricter than confidentiality, identity remains unknown to the research team

Single vs Double Blind

Single: Researcher knows but participants don't

Double: Neither researcher nor participants know

Placebo

An inactive substance that looks like the drug or treatment being tested

1938 Drug and Cosmetic Act

- Sulfanilamide Disaster

Required drug manufacturers to submit an application showing that new drugs were safe BEFORE marketing

Kefauver-Harris Amendment (1962)

- Thalidomide Tragedy

Tightened controls on drug safety, especially experimental drugs, and required that adverse reactions and contraindications must be labeled

Drug Regulation Overview

1862: US Dep. of Agriculture Formed - org. for sending out farm, agriculture, and food policies

1897: Tea Importation Act - Set standards for tea

1906: Pure Food and Drug Act - bans unlabeled drugs in food

Drug Regulation pt 2

1906: Food and Drug Asso. (FDA) - Regulates food, drug, and medication standards

1906: Meat Inspection Act - Assures that all legally sold meat passes FDA standards

1938: Food, Drug and Cosmetics Act - set laws so FDA could oversee safety of food, drug and cosmetics

Controlled Substances Act (1970)

All scheduled drugs/substances have potential for dependence and abuse

Schedule I vs Schedule V

- Schedule I are the most dangerous (Heroin, LSD, Weed, Meth, Peyote)

- Schedule V have the lowest potential for dependence and abuse (Antidiarrheals, Cough preparations)