Clinical Research process material for bpharmacy

clinical trial process material

1. Clinical Trial Process: An Clinical Trial Process: An
OverviewOverview
John O. Naim, Ph.D.John O. Naim, Ph.D.
Director, Clinical Trials Research Director, Clinical Trials Research
UnitUnit
West Virginia UniversityWest Virginia University
Mary Babb Randolph Cancer CenterMary Babb Randolph Cancer Center

2. What Is a Clinical Trial?What Is a Clinical Trial?
Effectiveness of intervention to treat a Effectiveness of intervention to treat a
diseasedisease
Safety of a new drugSafety of a new drug
Defining dose administrationDefining dose administration

Testing drug formulationTesting drug formulation
Exploring combination therapiesExploring combination therapies
Evaluating effect of therapies on quality of Evaluating effect of therapies on quality of
lifelife

3. Types of Clinical TrialsTypes of Clinical Trials

TreatmentTreatment
–Test new approaches to treat a diseaseTest new approaches to treat a disease

PreventionPrevention
–What approaches can prevent diseaseWhat approaches can prevent disease

Early-detection/screeningEarly-detection/screening
–What are new ways to find hidden diseaseWhat are new ways to find hidden disease

DiagnosticDiagnostic
–How can new tests or procedures ID diseaseHow can new tests or procedures ID disease

4. Phases of Drug DevelopmentPhases of Drug Development
Phase 1Phase 1Phase 2Phase 2Phase 3Phase 3Phase 4Phase 4
No. of No. of
ParticipantsParticipants
15-30 15-30 <100<100 100 to 100 to
thousandsthousands
Several Several
hundreds to hundreds to
several several
thousandsthousands
PurposePurpose First in First in
humanshumans
Find safe Find safe
dosedose
Determine Determine
efficacyefficacy
Compare Compare
new agent new agent
with with
standard standard
treatmenttreatment
Post –marketPost –market
Long-term Long-term
safety and safety and
efficacyefficacy

5. Who are the Players?Who are the Players?

Human Subject VolunteersHuman Subject Volunteers

Physician InvestigatorsPhysician Investigators

Research NursesResearch Nurses

PharmacistsPharmacists

Lab TechsLab Techs

Social WorkersSocial Workers

Data ManagersData Managers

6. Research Protocol: Roadmap Research Protocol: Roadmap

Detailed Research Plan that Includes:Detailed Research Plan that Includes:
–ObjectivesObjectives
–Background and RationaleBackground and Rationale
–Subject Selection CriteriaSubject Selection Criteria
–Treatment PlanTreatment Plan
–Study ProceduresStudy Procedures
–Response Evaluation CriteriaResponse Evaluation Criteria
–Statistical SectionStatistical Section

7. Human Research is Highly Human Research is Highly
RegulatedRegulated

Code of Federal Regulations (CFR)Code of Federal Regulations (CFR)
–Title 21- Food and DrugsTitle 21- Food and Drugs
»Part 50 Informed ConsentPart 50 Informed Consent
»Part 56 IRBPart 56 IRB
»Part 312 INDPart 312 IND
»Part 314 NDAPart 314 NDA
»Part 600, 6001 BiologicsPart 600, 6001 Biologics
»Part 812, 813, 814 Medical DevicesPart 812, 813, 814 Medical Devices
–Title 45- Public WelfareTitle 45- Public Welfare
»Part 46 Part 46 (subparts B, C, D) (subparts B, C, D) DHHS, Protection of Human subjectsDHHS, Protection of Human subjects

8. What About International What About International
Regulation?Regulation?

E6 Good Clinical Practice (GCP): E6 Good Clinical Practice (GCP):
Consolidated GuidanceConsolidated Guidance
–International ethical and scientific quality International ethical and scientific quality
standard for designing, conducting, recording standard for designing, conducting, recording
and reporting trial results.and reporting trial results.

9. Why is Human Research Highly Why is Human Research Highly
Regulated?Regulated?

Past transgressions lead to the need for laws Past transgressions lead to the need for laws
that protect the rights and welfare of human that protect the rights and welfare of human
subjects.subjects.
–Nuremberg Doctors Trial of 1946 (Nuremberg Code)Nuremberg Doctors Trial of 1946 (Nuremberg Code)
–Thalidomide Tragedy (Kefauver-Harris Amendment)Thalidomide Tragedy (Kefauver-Harris Amendment)
–Tuskegee Experiments (Belmont Report)Tuskegee Experiments (Belmont Report)
–Human Radiation ExperimentsHuman Radiation Experiments
–Gene Transfer ExperimentGene Transfer Experiment

10. Informed ConsentInformed Consent
Learning the key facts about a trial Learning the key facts about a trial before before
deciding whether to participate.deciding whether to participate.
–Research study purposeResearch study purpose
–Risks/BenefitsRisks/Benefits
–Alternative treatmentsAlternative treatments
–Confidentiality of recordsConfidentiality of records
–Medical treatment available if injury occursMedical treatment available if injury occurs
–Whom to contact for answers to questionsWhom to contact for answers to questions
–Statement that participation is Statement that participation is voluntaryvoluntary

11. Institutional Review BoardInstitutional Review Board
(IRB)(IRB)

All clinical trials must be approved and All clinical trials must be approved and
monitored by an IRB.monitored by an IRB.

IRB is an independent committee of IRB is an independent committee of
physicians, nurses, statisticians, community physicians, nurses, statisticians, community
advocates and others.advocates and others.

The function of the IRB is to ensure that a The function of the IRB is to ensure that a
clinical trial is ethical and the rights welfare clinical trial is ethical and the rights welfare
of study participants are protected.of study participants are protected.

12. Patient Recruitment ChallengePatient Recruitment Challenge

Poor patient recruitment is the number one Poor patient recruitment is the number one
reason that trials fail.reason that trials fail.

Only 3 to 5 percent of newly diagnosed Only 3 to 5 percent of newly diagnosed
adult cancer patients participate in a clinical adult cancer patients participate in a clinical
trial.trial.

Reasons for this relatively low number are Reasons for this relatively low number are
many.many.

13. Recruitment StrategiesRecruitment Strategies

Physician trust and contactPhysician trust and contact

Study staff contactStudy staff contact

Speaking to community groupsSpeaking to community groups

Newspaper and radio AdsNewspaper and radio Ads

Internet websites Internet websites

Physician referralsPhysician referrals

14. Subject Data CollectionSubject Data Collection

Data is collected on case report forms Data is collected on case report forms
(CRF)(CRF)

Much of clinical data is taken from the Much of clinical data is taken from the
subjects medical record (source documents)subjects medical record (source documents)

Pharmaceutical and device trials, data is Pharmaceutical and device trials, data is
verified by multiple playersverified by multiple players

15. Serious Adverse EventsSerious Adverse Events
Events that results in any of the following:Events that results in any of the following:
–Death or life-threateningDeath or life-threatening
–Hospitalization or prolonged hospitalizationHospitalization or prolonged hospitalization
–Persistent or significant disability/incapacityPersistent or significant disability/incapacity
–Congenital anomaly/birth defectCongenital anomaly/birth defect
Events that are serious, unexpected, and Events that are serious, unexpected, and
related or possibly related to participation in related or possibly related to participation in
the research must be reported to the the research must be reported to the
Sponsor, FDA and IRB in a timely manner. Sponsor, FDA and IRB in a timely manner.

16. Clinical Trial End ProductClinical Trial End Product

Ideal: Unambiguous conclusion regarding Ideal: Unambiguous conclusion regarding
the clinical outcome of the test the clinical outcome of the test
treatment/device. treatment/device.

Always strive for the ideal, but in most Always strive for the ideal, but in most
cases have to settle for the best comprise.cases have to settle for the best comprise.