Yesterday, today, and tomorrow. Goals of this presentation : A look at clinical research from a pharmacy point of view. What will NOT be a focus of.

Research PharmacyYesterday, today, and

tomorrow

Goals of this presentation :A look at clinical research from a pharmacy point of view.

What will NOT be a focus of this presentation:Social and ethical questions and considerationsLegal and regulatory issuesProtocol development and IND applicationsStatistical considerations in clinical trials

Why do we do research?Improve patient health through

improved patient care

Types of studies:Observational: e.g. epidemiologic,

cohort, case control, longitudinal, etcInterventional

Interventional clinical trialsClinical trials allow us to evaluate the efficacy and safety of new medications or agents

Usually in comparison to an established standard of care

Randomized, double-blind studies (the “Gold Standard”)

Why do we do interventional clinical trials?

To obtain data to present to the FDA !

Drug companies are trading drug (and medical care) for data on patient outcomes

Stages in drug developmentDrug discovery / developmentPre-clinical testingInvestigational New Drug application (IND)Clinical testing

Phase IPhase IIPhase IIIPhase IV

Phase I trials

First use of a new drug in humansSmall numbers of patients, usually healthy

volunteersLooking primarily at safety and dose

determinationSafety – dose limiting toxicity (DLT)Dose determination – increase dose to toxicity

Pharmacokinetic and pharmacodynamic studies

Phase II trials

Determine short-term risks and safetyLooking at effectiveness and best tolerated dose

levelDose(s) based on information from Phase I studies Also looking at side effectsStudy subjects are the types of patients the agent is

intended to treat

Phase IIILarge scale trials (e.g. 300 – 1000+ subjects)

looking at safety and efficacy usually in a randomized, controlled fashion often involving multiple centers

Seek to assess risk/benefit ratio and gather date for FDA approval of the agent / labeling

If data gathered from Phase I, Phase II, and Phase III trials demonstrate safety and efficacy => New Drug Application (NDA) may be filed with the FDA

Phase IV trials

Post approval studiesMay be required as a condition of approvalLong term safety studiesComparison studies

Important elements in clinical trials

The protocolThe informed consentRegulatory bodiesBlindingRandomizationFinance

The Study ProtocolCommon elements:

TitleProtocol summary or synopsisBackground and rationaleStudy design / investigational planRandomization and blindingThe investigational productInclusion and exclusion criteriaAdverse eventsData analysis

Informed Consent Form (the ICF)BackgroundElements

Description of trialVoluntariness / withdrawal of consent /

alternativesRisk / benefit ratioQuestionsContactsSignatures

Regulatory bodies

Institutional review board (IRB) – patient protection

Institutional bio-safety committee (IBC) and the Recombinant DNA Advisory Committee (RAC)

Food and drug administration (FDA)Compliance office / office of research

integrity (ORI)

BlindingSingle vs double blindPhysical blinding: Size, shape, taste,

appearance, smell, etc.Time considerationsDouble dummy designs

Randomization

HistoryIVR and IWR systemsStratificationBlocks

Finance

Contracts and grants (OCGM)Cost of doing a studyConflict of interest concerns

The “Players”PatientsThe PI (and sub I’s), the 1572 form

(Statement of Investigator)MonitorsResearch CoordinatorsRegulatory entities (IRB, IBC, FDA, ORI /

compliance, etc)CRO’s

The “Players” (continued)

Support servicesLaboratoryRadiologyPharmacyStatisticsFinance

In the beginning…“What’s this and where did it come from?” (x2)“…and you’re also in charge of investigational

drugs.”“I think it’s in that cabinet over there next to

the sink”“We are missing a week’s worth of entries on

the temp record.”“Is this the next envelope?”“I’m going to San Diego for a meeting!”“Budgets???”

The presentPersonnelTypes of studiesTrainingRecords and documentationMonitoringDisposal of study materials

Elements of a Research Pharmacy

PersonnelStorage space / equipmentTemperature monitoring Documentation / record retentionThe “information sheet” or “summary sheet”Study budget

Pharmacy study budgetsCommon Elements

Start-up MaintenanceRandomizationStudy drug preparation and dispensingClose-out feeOn – call fees

What’s ahead?

Why utilize pharmacy services?Exotic agentsElectronic data capture and recordsImpact of healthcare systemsCommunity based research