Research Pharmacy Yesterday today and tomorrow Goals of

Research Pharmacy Yesterday, today, and tomorrow

Goals of this presentation : ØA look at clinical research from a pharmacy point of view. Ø What will NOT be a focus of this presentation: Ø Social and ethical questions and considerations Ø Legal and regulatory issues Ø Protocol development and IND applications Ø Statistical 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, etc �Interventional

Interventional clinical trials �Clinical 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 development �Drug discovery / development �Pre-clinical testing �Investigational New Drug application (IND) �Clinical testing �Phase III �Phase IV

Phase I trials �First use of a new drug in humans �Small numbers of patients, usually healthy volunteers �Looking primarily at safety and dose determination �Safety – dose limiting toxicity (DLT) �Dose determination – increase dose to toxicity �Pharmacokinetic and pharmacodynamic studies

Phase II trials �Determine short-term risks and safety �Looking at effectiveness and best tolerated dose level �Dose(s) based on information from Phase I studies �Also looking at side effects �Study subjects are the types of patients the agent is intended to treat

Phase III �Large 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 studies �May be required as a condition of approval �Long term safety studies �Comparison studies

Important elements in clinical trials �The protocol �The informed consent �Regulatory bodies �Blinding �Randomization �Finance

The Study Protocol �Common elements: �Title �Protocol summary or synopsis �Background and rationale �Study design / investigational plan �Randomization and blinding �The investigational product �Inclusion and exclusion criteria �Adverse events �Data analysis

Informed Consent Form (the ICF) �Background �Elements �Description of trial �Voluntariness / withdrawal of consent / alternatives �Risk / benefit ratio �Questions �Contacts �Signatures

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)

Blinding �Single vs double blind �Physical blinding: Size, shape, taste, appearance, smell, etc. �Time considerations �Double dummy designs

Randomization �History �IVR and IWR systems �Stratification �Blocks

Finance �Contracts and grants (OCGM) �Cost of doing a study �Conflict of interest concerns

The “Players” �Patients �The PI (and sub I’s), the 1572 form (Statement of Investigator) �Monitors �Research Coordinators �Regulatory entities (IRB, IBC, FDA, ORI / compliance, etc) �CRO’s

The “Players” (continued) �Support services �Laboratory �Radiology �Pharmacy �Statistics �Finance

In the beginning… �“What’s this and where did it come from? ” (x 2) �“…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 present �Personnel �Types of studies �Training �Records and documentation �Monitoring �Disposal of study materials

Elements of a Research Pharmacy �Personnel �Storage space / equipment �Temperature monitoring �Documentation / record retention �The “information sheet” or “summary sheet” �Study budget

Pharmacy study budgets �Common Elements �Start-up �Maintenance �Randomization �Study drug preparation and dispensing �Close-out fee �On – call fees

What’s ahead? �Why utilize pharmacy services? �Exotic agents �Electronic data capture and records �Impact of healthcare systems �Community based research