Lecture 9: Drug Use, Access, and Role of Pharmaceutical Industry

Pharmaceuticals

most visible treatments in medical care; patients are familiar with pharmaceuticals because they are directly advertised to consumers (DTCA)

Pharmakon

greek word for drug, 3 meanings: remedy, poison, and magical charm

Pharmakon: Remedy

thought of as remedies when they reduce disease symptoms or eliminnate the disease

Pharmakon: Poisons

considered poisons for any harmful, unpleasant effect

Pharmakon: Magical Charm

many consider drugs as “magic bullet”, coined by Paul Ehrlich

Drugs

substances that produce a change in cellular of physiological functioning of humans

Social Values Affecting Perception and Drug Use

some drugs are illegal, some are highly restricted, some are easily available

Prescription

medication requiring a prescription by an authorized licensed health care provider

Non-prescription

medication available to the general public without a prescription aka OTC

Approved Use

medication is used for a condition that is approved to treat by the FDA

Unapproved/ Off-Label Use

medication is used for a condition that is not approved by FDA

Medicalization

defines a personal or social problem as a medical condition; necessitates treatment for problem; occurs when previous non-medical problems become defined as medical problems

Medicalization Examples

Articulation disorder (difficult in pronouncing specific types of sounds), obesity, ADHD

Problems with Medicalization

turns human differences into medical problems; medicine gets to define what is normal, brings too much medication use, consumers are at risk of side effects

Drugs Aspect that People Pay Attention To: Manufacturers

focus on a drug’s therapeutic effect with the goals of optimizing biochemical activity, increasing specificity, limiting negative effects

Drugs Aspect that People Pay Attention To: Healthcare Providers

concerned a drug’s therapeutic effects and treating their patients quickly and efficiently

Drugs Aspect that People Pay Attention To: Consumers/Patients

concerned about effects, adverse events, costs

Consumer’s Perspective

patients are end users for drugs, consumers make the final decision about whether or not they will use a drug; side-effects of drug influence consumers decisions to take the medication; consumers take a medication when they are confident the desired treatment effect with minimal side effects

Consumer’s Perspective: Possible Actions Taken for a Perceived Health Problem

do nothing, take action: begin self care with OTC or herbal remedy, or seek care from physician

Prescriber’s Perspective

to treat patients’ health problems, prescribers recommend lifestyle changes, physical therapy or surgery; prescription for drug therapy is one of the most common expected recommendation; prescribing enhances the interaction, symbolizing healing, and provides a sense of satisfaction to patient

Prescriber’s Perspective: Factors Influencing Prescribing Behavior

education (training in pharmacotherapies), colleagues or other health care providers, demands by consumers and society, promotional activities by drug manufacturers

Dispenser’s Perspective

much of filling prescription work has been automated by robots; internet sales of prescriptions and mail order delivery; pharmacists spend more time checking and verifying prescriptions already filled by robots or techs; pharmacists need to spend more time reviewing, recommending, and monitoring patient therapies, and provided patient centered care

FDA Determines

which drugs are allowed to be sold and prescribed in the U.S., which drugs are categorized as Rx and non-Rx drugs

Food, Drug, Cosmetic Act (1938)

guides how FDA regulates small molecules and hormones

Public Health Service Act (1994)

regulates biologic drugs, much larger molecules and more complex than small molecule drugs

FDA’s Functions

approval of drugs based on purity, safety, and effectiveness; regulation of labeling and advertising, good manufacturing practices and recalls if necessary, bioequivalence standards, postmarketing surveillance for unanticipated problems after approval; monitoring the safety of the nation’s blood supply

Non-FDA Approved (Off-Label) Indications

uses of a product that were not approved by FDA, but have shown value after approval based on post-marketing research; cannot be promoted by manufacturer

Drug Development Process

drug discovery research, preclinical testing, clinical testing, new drug application (NDA) submitted for approval

Drug Development Process: Discovery Research

bench research, identifies potentially useful compounds

Drug Development Process: Preclinical Testing

animal testing

Drug Development Process: Clinical Testing

testing on humans, three phases prior to approval

Clinical Testing: Phase 1

determines safe dosage range, preferred route of administration, mechanisms of absorption, distribution, elimination, and possible toxicities; healthy volunteers ( < 100), lasts approx. 1 - 1.5 years

Clinical Testing: Phase 2

safety and efficacy in treating a disease or symptom; volunteers with that disease of symptom ( < 300); last approx. 2 years

Clinical Testing: Phase 3

safety, efficacy and dosage range under market conditions; monitor adverse drug effects from long term use; volunteers with that disease or symptom ( < 3000), lasts approx. 3 - 3.5 years

Approval

firms submit a new drug application (NDA); FDA has 60 days to decide to review or refuse for completeness

Approval: FDA’s Center for Drug Evaluation and Research (CDER) Reviews

10 months for routine, 6 months for priority reviews; inspects manufacturing facility, may deny or request more information/hearing

Clinical Testing: Phase 4

safety and effectiveness of drugs and look for any side effects that may have been missed in earlier trials

Approval: Drug Has Been Approved for Market

moves on to clinical testing phase 4

Supplemental NDA (sNDA)

used if firms want to alter the drug’s ingredients, dosage, manufacturing, or labeling; submitted to FDA to get these changes approved

Abbreviated NDA

submitted to demonstrate that generic products are bioequivalent with the brand name drugs

Generics Products or Biosimilars

created to be the same as existing brand-name drugs that were already approved

Generic Products/Biosimilars Abbreviated NDA Rules

generic products/biosimilars are expected to be identical with brand-name drugs in terms of potency, dosage form, and labeling, the FDA does not require any pre-clinical or clinical data; manufacturers of generic products do not have to submit IND or NDA; lower clinical trial burden than manufacturers of original product

Pharmaceutical Equivalence

drugs that have the same active ingredient(s), the same dosage form, and the same strength; color, taste, and other features may be different

Bioequivalence

drugs that have the same rate and extent of absorption into the bloodstream as the brand drug

Therapeutic Equivalence

drug is therapeutically equivalent to the comparable brand when the FDA says the generic is safe and effective; Pharmaceutical Equiv + Bioequiv = therapeutic equiv

Drug Pricing

largest component of drug costs are research and development costs; once a drug is fully developed and tested, relatively little cost is needed in producing and providing the drug, but the drug development process is very expensive

Drug Pricing Is Based On

costs and profits of supply chain plus any discounts and economic forces; manufacturer’s cost + profit, R&D costs, wholesaler’s cost + profit, retailer’s cost + profit, discounts, supply and demand

Importation

many firms located outside the U.S. are developing and producing drugs outside the U.S.; however these products can be sold as prescription drugs; FDA must approve the manufacturing process and plant where the drugs are produced; currently against the law to purchase prescription drugs in another country for using them in the U.S.

Counterfeit Drug

fake medicine; may be contaminated, may contain wrong or no active ingredient, may include active ingredient but at wrong dose, illegal because it may be harmful; particularly a problem in developing world, over 30% of drugs sold in developing world are counterfeit

Consumer Risks

receive no benefits from drugs when there is no active ingredient; experience adverse effects (or even death) from drugs with harmful and toxic chemicals; can delay consumers’ access to effective treatment

Foreign Trials

clinical trials are conducted outside the U.S.; allows for diverse populations in the trials, FDA not equipped to inspect many foreign clinical trials sites’ can be hard to tell why patient outcomes differ between sites; each site may have different standards, limiting the ability to interpret the data

Intellectual Property Rights (IPRs)

laws and regulations to protect ideas and products of innovators

IPRs for Small Molecule Drugs

regulated the Hatch-Waxman Act of 1984; data exclusivity period and patent protection to innovators; copies considered genetics

IPRs for Biologics

regulated by the Patent Protection and Affordable Care Act (PPACA) of 2010; data exclusivity period and patent protection to innovators; copies considered biosimilars