Ethics in Clinical Research & Drug Approval PDF

# ETHICS - **Values** - Right - Morals - Benefit - **Dilemma** - Compliance - Wrong ## Core Ethical Principles - Respect for Persons - Autonomy (Right to Make Decisions) - Beneficence DO NO HARM - Justice Be Fair ### Respect for Persons - Pt should be treated as a...

# ETHICS - **Values** - Right - Morals - Benefit - **Dilemma** - Compliance - Wrong ## Core Ethical Principles - Respect for Persons - Autonomy (Right to Make Decisions) - Beneficence DO NO HARM - Justice Be Fair ### Respect for Persons - Pt should be treated as and independent person capable of making decisions. - Pt's w/decreased ability to make decisions should be protected - Pt's have the right to know about alternative health care options and the risks taking those options entail ### Autonomy - Right to self-determination - Must respect pt.'s right to make decision even if we feel it is not the best decision. ### Informed Consent re Clinical trials - Right to be informed - Right that participation is voluntary and without coercion ### Beneficence: (DO NO HARM) - Duty to protect research subjects from harm. - Ensures the risks and benefits from participating in a research study are clearly defined. - If a serious side effect is noted researchers have an obligation to d/c the study ### Risk-Benefit Ratio - All possible consequences of a clinical study must be analyzed an balanced against the inherent risks - Risks to subjects must be reasonable in relation to the anticipated benefits ### Justice - Selection of subjects bust be fair across all social classes and racial and ethnic groups # The Drug Approval Process - Up to 9 years - Preclinical Assessment - Compound optimization - in vitro and in vivo studies - Drug target Identification - Validation - Pharmacology & toxicology - Animal assays - ADME - Basic research - Genetics - Understanding Pathophysiology - Clinical Development - Phase 1 - 20-100 healthy volunteers - Safety and tolerability - PK-PD - Phase 2 - 100-300 patients - Dose optimization - Safety and efficacy - Phase 3 - 1000-5000 patients - Pivotal trials - Efficacy, side effects - Safety and efficacy - Large scale studies - Patients - Post marketing surveillance - Up to 6 years - 10-15 years - approx. $2.6 B **FDA** regulates research and development - Must follow good clinical practice consolidated guidelines ## Preclinical trials - Used to determine drugs toxic and pharmacologic effects. - Testing is done both invitro and in vivo on animals ## Human Clinical Experimentation - **Phase 1** - Test on small group of people (20-100 healthy volunteers) - Determine safe dose range and tolerability - Determine side effect/pharmacodynamics and pharmacokinetics - **Phase 2** - Given to a larger group of people (100-300 patients) - Further evaluate safety and dose optimization - Determine effectiveness - **Phase 3** - Even larger group of people (1000-5000 patients) - Confirm effectiveness, monitor side effects - Compare with commonly used treatments - Collect data to allow for safe usage of medication - **Phase 4** - Continued monitoring of effectiveness and side effects - Determine long-term effects # Clinical Research Study - **Independent variable** - treatment or drug - **Dependent variable** - outcome - **Intervening variable** (may interfere with study results) - Age - Sex - Disease state - Diet - Subjects social environment - **Independent variable:** treatment such as with a drug - **Dependent variable:** outcome, such as clinical effect - **Experimental group:** receives the drug being tested - **Control group:** may receive no drug, a different drug, a placebo (pharmacologically inert substance) or the same drug with a different dose route or frequency of administration. # American Nurses Association ## Code of Ethics - "Was developed as a guide for carrying out nursing responsibilities in a manner consistent with quality in nursing care and the ethical obligations of the profession." ## The Nurses role in clinical research - Responsible for patient safety - Responsible for integrity of research protocol - Adopted in 1950 - Revised in 2015 to incorporate advances in nurse leadership social policy, global health, social medial, emr and the nurse's expanded role in clinical research. # Clinical Judgement: Clinical Research ## Safety - Protect pt. from actual or potential harm ### Recognizing Cues - Identify eligible patients - Assess response to the study agent - Identify adverse events ### Analyze cues/prioritize hypotheses - Need for health teaching - Potential for decreased adherence ### Generate Solutions - Have process in place to identify eligible participants - Provide education for both participants and staff - Plan participant care to ensure integrity and compliance with study protocol ### Take Action - Support the process of informed consent in a culturally competent manner. - After reviewing the study protocol, administer study agent(s). - Accurately and safely collect biospecimens. - Accurately document all participant care, assessment findings, and study agent administration. - Act as advocate, educator and collaborator in the research process ### Evaluate Outcomes - Determine if potential participant understand what it means to participate in a study - Monitor response to the study agent and/or other interventions # Drug Standards and Legislation - **Drug standards:** - United States Pharmacopeia and the National Formulary - The International Pharmacopeia - **Federal legislation:** - 1912: The Sherley Amendment - 1938: The Federal Food, Drug, and Cosmetic Act - 1970: The Comprehensive Drug Abuse Prevention and Control Act - 1994: Dietary Supplement Health and Education Act - 1996: Health Insurance Portability and Accountability Act - 2010: Patient Protection and Affordable Care Act - 2012: Food and Drug Administration Safety and Innovation Act - **United States Pharmacopeia and National Formula:** - Authoritative source for drug standards, forms, drug substances etc. published annually - **International Pharmacopeia:** - First published in 1951 by WHO provides a basis for standards in strength and composition of drugs throughout the world. - **1912 The Sherley amendment:** prohibited false therapeutic claims - **1938 The Federal Food, Drug and Cosmetic Act:** Empowered the FDA to ensure a drug was safe before marketing - **The Comprehensive Drug Abuse Prevention and control Act:** Promotion of drug education and research into the prevention and treatment of dependence - Promotion, education and research into the prevention and treatment of dependence - Strengthening of enforcement authority - Establishment of treatment and rehabilitation facilities - Designation of schedules or categories of controlled substances according to abuse liability - **Dietary Supplement Health and Education Act:** established labeling requirements and authorized the FDA to promote safe manufacturing practices - **Health Insurance Portability and Accountability Act:** provided patients more control over their health information, including boundaries on the use and release of health records - **Patient Protection and Affordable Care Act:** - Quality, affordable health care for all Americans - Improved quality and efficiency of health care - Prevention of chronic disease and improved public health - Improved access to innovative medical therapies - Community living services and support # Schedule Categories for Controlled Substances - **Schedule I** - Not acceptable for medical use... high potential for abuse (LSD, heroin)... illegal - **Schedule II** - High potential for abuse or physical dependence (Methamphetamine, hydromorphone) - **Schedule III** - Moderate to low potential (low dose hydrocodone (acetaminophen w/codeine), ketamine) - **Schedule IV** - Low potential for abuse (diazepam, lorazepam) - **Schedule V** - Lower than Sch IV (low dose codeine with guaifenesin or promethazine) - **Table 2.1 pg. 14:** - Ex. Schedule II: Methadone when used for medical purposes such as withdrawal - Ex. Schedule V: Low dose codeine >200 mg p/100 mL - ***Controlled substances must be wasted w/another medical professional if entire vial is not administered.*** # Nurse Practice Acts - **Important website links:** - www.leg.state.fl.us - www.floridanursing.gov - www.ncsbn.org - Provide guidance for drug administration by nurses (i.e. cannot prescribe or administer drugs without a health care provider order) # Combating Drug Counterfeiting - **FDA and consumer group strategies** - Tougher oversight of distributors - Rapid alert system - Better informed consumers - Verified Internet Pharmacy Practice Site - www.fda.gov/Safety/MedWatch/HowToReport/ - **Counterfeit drugs** - May contain incorrect ingredients - May have insufficient amounts of active ingredients - May have no active ingredients - May contain impurities and contaminants - May be distributed in fake packaging - **Role of nurse: Consumer education** - Unexpected side effects - Different tastes - Unapproved internet sites - Different packaging # Drug Names - **Chemical names** - hydroxyacetanilide - **Generic names** - acetaminophen - **Brand/trade names** - Tylenol - **Chemical Name:** Describes the chemical structure (Lowercase) - **Generic Name:** the official, nonproprietary name of the drug, the name is not owned by any drug company, universally accepted. (80% of drugs in US are sold under the generic name) (lowercase) - **Brand/Trade Name:** AKA proprietary names, chose by the drug company and is usually a registered trademark. (Uppercase) - Health care providers and patients must exercise care when choosing generic drugs because of possible variations in their action or in patient's response to them - Patient's should be cautions not to change generic drug manufacturers - Health care providers must note on prescriptions whether the pharmacist may substitute the generic when the brand name is prescribed. # OVER-THE-COUNTER DRUGS - **OTC drugs** - Found to be safe and appropriate for use without direct supervision of health care provider - Available without a prescription - **In 2002, FDA standardized OTC labeling** - Provide consumers with information - Active and inactive ingredients with amount in each dosage unit - Purpose of product - Uses or product - Specific warnings - Dosage instructions - Describes benefits and risks with OTC drug - **In 2002, FDA standardized OTC labeling** - Provide consumers with information - Active and inactive ingredients with amount in each dosage unit - Purpose of product - Uses or product - Specific warnings - Dosage instructions - Describes benefits and risks with OTC drug - **Box 2.3 pg. 17 nursing considerations r/t OTC Drugs** # Drug Resources - American Hospital Formulary Service Drug Information - U.S. Pharmacopeia-Drug Information - Medical Letter - Prescriber's Letter - MedlinePlus: www.nlm.nih.gov/medlineplus/druginformation - The Handbook of Nonprescription Drugs - Credible internet websites