demystifying clinical trials - capital...

Demystifying Clinical TrialsBridging the Gap From Research to Patient Care

Demystifying Clinical TrialsBridging the Gap From Research to Patient Care

Myra Woolery-Antill, MN, RN

Pediatric Clinical Nurse Specialist

Nursing and Patient Care Services

Warren Grant Magnuson Clinical Center

National Institutes of Health

Barb Biedzycki, MSN, RN, NP

Nurse Practitioner

Sidney Kimmel Comprehensive Cancer Center

at Johns Hopkins

ObjectivesObjectives

! Describe the different phases of clinical trials

! Identify the differences between clinical and research aspects of care including the importance of research assessment, data collection,and documentation

! Discuss implications for patients and families including ethical issues

National Institutes of Health (NIH)National Institutes of Health (NIH)

The Mark O. HatfieldClinical Research Center

Opening December 2004

Warren Grant Magnuson

Clinical Center

Sponsors of Clinical TrialsSponsors of Clinical Trials

!! NIH Sponsored ProgramsNIH Sponsored Programs!! IntramuralIntramural

!!ExtramuralExtramural!! Cooperative groupsCooperative groups

!! Comprehensive cancer centersComprehensive cancer centers

!! Community based research programsCommunity based research programs

!! Pharmaceutical companiesPharmaceutical companies

http://http://clinicaltrialsclinicaltrials..govgov//

What Are Clinical Trials?What Are Clinical Trials?

!Answer a question! Investigate a problem!Determine the efficacy of

an intervention

Clinical research designed to

http://www.cancer.http://www.cancer.govgov//clinicaltrialsclinicaltrials/learning/what/learning/what--isis--aa--clinicalclinical--trialtrial

Types of Clinical TrialsTypes of Clinical Trials

! Preventative! Screening & Early Detection! Diagnostic! Natural History! Therapeutic! Supportive! Genetic and Family

Examples of Clinical TrialsExamples of Clinical Trials

! Prospective! Retrospective! Longitudinal! Cross-sectional! Psychosocial! Behavioral

Obstacles to ConductingClinical TrialsObstacles to ConductingClinical Trials

!! FundingFunding

!! Inadequacies within the science of Inadequacies within the science of clinical trialsclinical trials

!! Inadequate accession of clinical trialsInadequate accession of clinical trials

!! Ethical concernsEthical concerns

!! Professional territorial issuesProfessional territorial issues

Elements of Clinical TrialsElements of Clinical Trials

!High probability of generating useful knowledge

!Benefits

!Selection of subjects

! Informed consent

!Subject’s rights

RisksRisks BenefitsBenefits

RisksRisksBenefitsBenefits RisksRisks

BenefitsBenefits

Protection of Research ParticipantsProtection of Research Participants

http://www.http://www.hhshhs..govgov//ohrpohrp//

http://http://cmecme.cancer..cancer.govgov//clinicaltrialsclinicaltrials/learning//learning/humanparticipanthumanparticipant--protections.aspprotections.asp

Guidelines and Regulations for Clinical ResearchGuidelines and Regulations for Clinical Research

19471947 Nuremberg Code Nuremberg Code (http://(http://ohsrohsr..odod..nihnih..govgov/guidelines//guidelines/nurembergnuremberg.html).html)

19641964 HelsinskiHelsinski DeclarationDeclaration(http://www.(http://www.fdafda..govgov//ococ/health/helsinki89.html)/health/helsinki89.html)

19741974 National Commission for the National Commission for the Protection of Human Subjects of Protection of Human Subjects of Biomedical and Behavioral ResearchBiomedical and Behavioral Research(http://www.(http://www.fasfas..harvardharvard..eduedu/~research/PL93/~research/PL93--348.html)348.html)

19791979 Belmont ReportBelmont Report((http://www.http://www.fdafda..govgov//ococ//ohrtohrt//irbsirbs//belmontbelmont.html).html)

Clinical Trial DevelopmentClinical Trial Development

““ReadyReady,, FireFire, , AimAim!”!”

Clinical Trial PhasesClinical Trial Phases

Phase IPhase I

Phase IIPhase II

Phase IIIPhase III

Phase IVPhase IV

http://www.cancer.http://www.cancer.govgov//clinicaltrialsclinicaltrials/learning/clinical/learning/clinical--trialstrials--educationeducation--seriesseries

Phase I Clinical TrialsPhase I Clinical Trials

! Establish maximum tolerated dose and dosing schedule

! Determine drug pharmacology! Identify side effects & toxicities

Adult Phase I Clinical TrialsAdult Phase I Clinical Trials

! Small dose of drug arbitrarily chosen

! Dose given to 15 - 80 subjects! Toxicity monitored & dose

increased! Continue escalating until side

effects are not tolerable (MTD)

Pediatric Phase I Clinical TrialsPediatric Phase I Clinical Trials

! Single agent! Dose Escalation

! Starting dose usually 50 - 80% of adult MTD

! Dose increased by 20% increments

! Usually pharmacologically guided

Phase II Clinical TrialsPhase II Clinical Trials

! Determine antitumor activity in specific cancers

! Determine effectiveness of drug for particular indication(s)

! Determine intervention effects! Gather additional toxicity

information to determine common short term effects

Phase III Clinical TrialsPhase III Clinical Trials

! Prospectively compare:! Investigational therapy

against standard treatment! New intervention with

standard intervention! Gather additional information

about effectiveness & safety

Phase III Clinical TrialsPhase III Clinical Trials

Stratification may be needed to assure balance

Randomization

Pictures Not Available

Phase IV Clinical TrialsPhase IV Clinical Trials

! Delineates additional information about drug’s risk, benefits, and optional use

! Study of different doses and/or schedules of administration

! Integrate investigative treatment with other treatment modalities

Protocol ComponentsProtocol Components

objectivesBackground & Rationale Inclusion

Criteria

Exlcusion

Criteria

Treatment PlanPatient

Monitoring Criteria

Response Criteria

Statistical Considerations Consent Form

http://http://ctepctep.cancer..cancer.govgov/guidelines/templates.html/guidelines/templates.html

Toxicity CriteriaToxicity Criteria

Toxicity Criteria for Toxicity Criteria for MyelosuppressionMyelosuppression

National Cancer InstituteNational Cancer InstituteToxicityToxicity Grade 0Grade 0 Grade 1Grade 1 Grade 2Grade 2 Grade 3Grade 3 Grade 4Grade 4

WBCWBC > 4000> 4000 3000 3000 -- 39003900 2000 2000 -- 29002900 1000 1000 -- 19001900 < 1000< 1000

NeutrophilsNeutrophils > 2000> 2000 1500 1500 -- 19001900 1000 1000 -- 14001400 500 500 -- 900900 < 500< 500

LymphoctesLymphoctes > 2000> 2000 1500 1500 -- 19001900 1000 1000 -- 14001400 500 500 -- 900900 < 500< 500

InfectionInfection NoneNone MildMild ModerateModerate SevereSevere Life Life threateningthreatening

HemoglobinHemoglobin WNLWNL normal normal -- 10.010.0 8 8 -- 10.010.0 6.5 6.5 -- 7.97.9 < 6.5< 6.5

PlateletsPlatelets WNLWNL normal normal -- 75 K75 K 50 K 50 K -- 74,99974,999 25 K 25 K -- 49.9 K49.9 K < 25,000< 25,000

http://http://ctepctep.cancer..cancer.govgov/reporting//reporting/ctcctc.html.html

Informed ConsentInformed Consent

!! Purpose of study and expected study participation durationPurpose of study and expected study participation duration!! Description of drug, procedures, treatments and interventionsDescription of drug, procedures, treatments and interventions!! Description of foreseeable risks or discomfortsDescription of foreseeable risks or discomforts!! Description of benefits from study (subjects & others)Description of benefits from study (subjects & others)!! Alternative procedures or treatment optionsAlternative procedures or treatment options!! Statement of confidentialityStatement of confidentiality!! Compensation for injuryCompensation for injury!! Names and numbers of persons to contactNames and numbers of persons to contact!! Participation is voluntaryParticipation is voluntary

http://www.http://www.hhshhs..govgov//ohrpohrp//humansubjectshumansubjects/guidance//guidance/icic--nonnon--e.e.htmhtm

http://www.http://www.fdafda..govgov//ococ//ohrtohrt//irbsirbs//informedconsentinformedconsent.html.html

Research Research Nurse Nurse

CoordinatorCoordinator

PatientPatient

InvestigatorInvestigator

Clinical Clinical NurseNurse

Clinical Nurse Role Clinical Nurse Role Clinical Nurse Role

!! AdvocateAdvocate!! EducatorEducator!! LiaisonLiaison!! Patient MonitorPatient Monitor!! Data CollectorData Collector!! CommunicatorCommunicator!! FollowFollow--upup

Nursing Role in Clinical TrialsNursing Role in Clinical Trials

AdvocacyAdvocacy!! Promote open communicationPromote open communication!! Encourage discussionsEncourage discussions!! Ensure adequate information is givenEnsure adequate information is given!! Assist family in defining their goals Assist family in defining their goals

and purpose for participationand purpose for participation!! Assess patient’s understanding of Assess patient’s understanding of

risk vs. benefit risk vs. benefit !! Support familySupport family


EducationEducation!! Clinical trialClinical trial

!! Protocol requirementsProtocol requirements

!! Medication administrationMedication administration

!! Side effects and symptom Side effects and symptom managementmanagement

!! SelfSelf--care measurescare measures

!! Resources availableResources available


Patient MonitoringPatient Monitoring!! AssessmentAssessment

!! Identification of side effectsIdentification of side effects

!! Response to interventionResponse to intervention

!! Data CollectionData Collection!! Specimen collectionSpecimen collection

!! DocumentationDocumentation

Bridging the GapBridging the Gap

Comparison of Clinical and Research Aspects of CareComparison of Clinical and Research Aspects of Care

!! AssessmentAssessment

!! InterventionsInterventions

!! Laboratory & Diagnostic StudiesLaboratory & Diagnostic Studies

!! Medications Medications

!! Care Conferences Care Conferences

!! TeachingTeaching

!! Coordination of ServicesCoordination of Services


AssessmentAssessment

Identifying Toxicities Identifying Toxicities Patient DiaryPatient DiaryPatient Diary

FilgrastimFilgrastim/Research Drug/Research Drug

Name: __________ Dose: _____ Cycle Number: ____ Cycle Start DaName: __________ Dose: _____ Cycle Number: ____ Cycle Start Date: ______ Drug Start Date: _________te: ______ Drug Start Date: _________

FeverFever

HeadachesHeadaches

Muscle achesMuscle aches

Bone or joint painBone or joint pain

SIDE EFFECTSSIDE EFFECTS

Daily temperatureDaily temperature

Indicate reason for missed dose*Indicate reason for missed dose*

Time dose givenTime dose given

DateDate

* If you missed a dose write “M” in the box* If you missed a dose write “M” in the box.

Follow-upFollow-up Comparison of Clinical and Research Aspects of CareComparison of Clinical and Research Aspects of Care

InterventionsInterventions!! Management and effectivenessManagement and effectiveness

!! Response to therapy or treatmentResponse to therapy or treatment


Laboratory and Diagnostic StudiesLaboratory and Diagnostic Studies!! Routine labs and diagnostic studies Routine labs and diagnostic studies

!! Research specimensResearch specimens

!! Blood limitsBlood limits

!! Drug levelsDrug levels

!! Pharmacokinetics and serial blood testsPharmacokinetics and serial blood tests

PharmacokineticsPharmacokineticsPharmacokinetics

Studies performed to determine Studies performed to determine the absorption, distribution, the absorption, distribution, metabolism, and excretion of metabolism, and excretion of investigational agents as well investigational agents as well as their effects on the bodyas their effects on the body

PharmacokineticsPharmacokineticsPharmacokineticsNursing Considerations in

Pharmacokinetics/Serial BloodsNursing Considerations in Nursing Considerations in

Pharmacokinetics/Serial BloodsPharmacokinetics/Serial Bloods

!! IV accessIV access

!! Sampling siteSampling site

!! Medication administrationMedication administration


!! Sampling timeSampling time

!! Transporting specimensTransporting specimens

PK WorksheetPK WorksheetPK Worksheet

FilgrastimFilgrastim/Research Drug Pharmacokinetic Worksheet/Research Drug Pharmacokinetic Worksheet

Patient Name:______________________ SPatient Name:______________________ Study ID#:_______________tudy ID#:_______________

Height (cm): ________ Weight (kg): __________ Height (cm): ________ Weight (kg): __________ BSA : _____________BSA : _____________

FilgrastimFilgrastim/Research Dose (mcg): _______ Date: _____________ Time : _/Research Dose (mcg): _______ Date: _____________ Time : _____________

6 hr post6 hr post6622





Pre dosePre dose1111

Central Central

Line or PIVLine or PIV

Actual Actual TimeTimeTime DueTime DueTimeTimeDateDateSample #Sample #DayDay

R115777 Biologic EffectsR115777 Biologic Effects

0

500

1000

1500

2000

2500

3000

3500

4000

Pre Steady State

165 mg/m 2

200 mg/m 2

275 mg/m 2

375 mg/m 2

FTaseActivity

(cpm)

0

500

1000

1500

2000

2500

3000

3500

4000

Pre Steady State

165 mg/m 2

200 mg/m 2

275 mg/m 2

375 mg/m 2

FTaseActivity

(cpm)

Inhibition of Inhibition of FarnesyltransferaseFarnesyltransferase

PK StudiesPK StudiesPK Studies

DrugDrugConcentrationConcentration

TimeTime

Pharmacokinetic SamplingPharmacokinetic SamplingPharmacokinetic Sampling

!!LabelingLabeling

!!TransportationTransportation

!!ProcessingProcessing

!!DocumentationDocumentation


MedicationsMedications!! VerificationVerification


!! Side effectsSide effects


Care ConferencesCare Conferences!! Guided by clinical or research aspectsGuided by clinical or research aspects


TeachingTeaching!! Disease process and symptom managementDisease process and symptom management

!! MedicationsMedications

!! MonitoringMonitoring

!! Self CareSelf Care

!! NotificationNotification


Coordination of ServicesCoordination of Services!! CommunicationCommunication

!! Medication preparation and deliveryMedication preparation and delivery

Case ScenariosCase Scenarios Adult Case StudyAdult Case Study

Ms. T. G. is a semiMs. T. G. is a semi--retired R.N. newly retired R.N. newly diagnosed with stage IV pancreatic cancerdiagnosed with stage IV pancreatic cancer

Eager to join phase II vaccine study because Eager to join phase II vaccine study because she heard it makes a difference and she she heard it makes a difference and she doesn’t want to diedoesn’t want to die

Disease progression ……continues on studyDisease progression ……continues on study

Ethical IssuesEthical Issues

Respect for personsRespect for persons

AutonomyAutonomy

SelfSelf--determination determination

PrivacyPrivacy

National Commission for the Protection of Human Subjects of ReseNational Commission for the Protection of Human Subjects of Research (1979). The arch (1979). The Belmont Report: Ethical Principles and Guidelines for the ProtecBelmont Report: Ethical Principles and Guidelines for the Protection of Human tion of Human Subjects for Research. Available at Subjects for Research. Available at www.www.fdafda..govgov//ococ//ohrtohrt//irbsirbs//belmontbelmont.html.html

Potential Research CandidatePotential Research Candidate

Mrs. D. P.Mrs. D. P.

!! 57 year old widow with 2 adult children57 year old widow with 2 adult children!! Newly diagnosed with multiple myelomaNewly diagnosed with multiple myeloma!! Interested in a phase I vaccine research Interested in a phase I vaccine research

studystudy

The Ethical IssuesThe Ethical Issues

The Belmont ReportThe Belmont Report

!! Respect for personRespect for person!! BeneficenceBeneficence!! JusticeJustice

National Commission for the Protection of Human Subjects of ReseNational Commission for the Protection of Human Subjects of Research arch (1979). The Belmont Report: Ethical Principles and Guidelines fo(1979). The Belmont Report: Ethical Principles and Guidelines for the r the Protection of Human Subjects for Research. Available at Protection of Human Subjects for Research. Available at www.www.fdafda..govgov//ococ//ohrtohrt//irbsirbs//belmontbelmont.html.html

The Next VisitThe Next Visit

Mrs. D. P., her daughter, and 3 grandchildrenMrs. D. P., her daughter, and 3 grandchildren

Illiteracy does not equal incompetence.Illiteracy does not equal incompetence.

Comprehension is relative.Comprehension is relative.

Factors associated with a greater knowledgeFactors associated with a greater knowledge

!! College educationCollege education!! Speak only English at homeSpeak only English at home!! Read consent carefullyRead consent carefully!! Time to considerTime to consider!! Nurse present Nurse present !! Received simplified consentReceived simplified consent

JoffeJoffe, S., Cook, E.F., Cleary, P.D., Clark, J.W., & Weeks, J.C. , S., Cook, E.F., Cleary, P.D., Clark, J.W., & Weeks, J.C. (2001). Lancet Vol.358:1772(2001). Lancet Vol.358:1772––77..

Consent GuidelinesConsent Guidelines

Be clear and concise.Be clear and concise.

Check reading level…Check reading level…

usually 8usually 8thth grade is okay.grade is okay.

Check for understanding frequently.Check for understanding frequently.

Pediatric Case ScenarioPediatric Case Scenario

KaitlynKaitlyn is a preschooler who has refractory stage IV is a preschooler who has refractory stage IV neuroblastoma. She has been referred to your neuroblastoma. She has been referred to your institution for the phase II protocol of institution for the phase II protocol of TemacideTemacide. Her . Her parents have been searching everywhere for treatment parents have been searching everywhere for treatment options and are desperate to be entered into this study. options and are desperate to be entered into this study.


Twenty subjects are to be accrued on the Twenty subjects are to be accrued on the TemacideTemacide study. study. KaitlynKaitlyn would be subject #7 if she meets eligibility criteria. would be subject #7 if she meets eligibility criteria.

"" Three of the six patients have died of disease progression Three of the six patients have died of disease progression

"" One patient is experiencing severe complications of the treatmenOne patient is experiencing severe complications of the treatment t regimenregimen

"" The remaining two subjects have stable disease and are The remaining two subjects have stable disease and are experiencing minimal to moderate side effectsexperiencing minimal to moderate side effects


!! Based on your knowledge of the research Based on your knowledge of the research findings should the study continue to accrue subjects?findings should the study continue to accrue subjects?

!! How should the findings be shared with the family during How should the findings be shared with the family during the informed consent process if at all?the informed consent process if at all?

!! How will the parents motives for participation influence How will the parents motives for participation influence their decision?their decision?

!! Do you believe this family can give an informed consent Do you believe this family can give an informed consent that is in the best interest of their child?that is in the best interest of their child?

Adolescent Case ScenarioAdolescent Case Scenario

Michael is a 15 year who presents to your clinical setting to ruMichael is a 15 year who presents to your clinical setting to rule le out Sarcoma. out Sarcoma.

He is accompanied by his parents. His family informs you they He is accompanied by his parents. His family informs you they do not want him to know his potential diagnosis.do not want him to know his potential diagnosis.

After completing diagnostic work up, he is eligible for the After completing diagnostic work up, he is eligible for the Sarcoma research protocol. Sarcoma research protocol.

Adolescent Case ScenarioAdolescent Case Scenario

!! Is it acceptable to enter a teenager who does not Is it acceptable to enter a teenager who does not know their diagnosis on a research study?know their diagnosis on a research study?

!! How do you obtain an informed assent or do you?How do you obtain an informed assent or do you?

!! How do you respect the parent’s wishes but maintain How do you respect the parent’s wishes but maintain honesty with Michael?honesty with Michael?

!! What do you do if Michael asks you why the other What do you do if Michael asks you why the other children in the clinical setting are bald?children in the clinical setting are bald?

!! How would you teach him about treatment side How would you teach him about treatment side effects and management?effects and management?

Ethical Issues in PediatricEthical Issues in PediatricEthical Issues in Pediatric

!!Informed consentInformed consent

!!Truth tellingTruth telling

!!Minor assentMinor assent

!!FutilityFutilityhttp://www.http://www.hhshhs..govgov//ohrpohrp/children//children/

http://www.http://www.fdafda..govgov//ococ//ohrtohrt//irbsirbs//informedconsentinformedconsent.html#children.html#children

RisksRisks BenefitsBenefits Slide Not Available

QuestionsQuestions

Slide Not Available

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