Recruitment in Recruitment in Cancer TrialsCancer Trials

Dr. Bhaswat S. ChakrabortyDr. Bhaswat S. ChakrabortyVP, R & D, CadilaVP, R & D, Cadila

Patient Participation in Patient Participation in Cancer TrialsCancer Trials

A 1999 press release from the American A 1999 press release from the American Society of Clinical OncologistsSociety of Clinical Oncologists only 3% of adults with cancer participate in only 3% of adults with cancer participate in

clinical trialsclinical trials far fewer than the number needed to answer far fewer than the number needed to answer

the most pressing cancer questions quickly the most pressing cancer questions quickly

Up to 80% of clinical trials are estimated Up to 80% of clinical trials are estimated to experience problems with recruitment to experience problems with recruitment

A Survey on Clinical Trial A Survey on Clinical Trial BarriersBarriers

A survey of almost 6,000 people with cancer A survey of almost 6,000 people with cancer conducted in 2000conducted in 2000 85% were either unaware or unsure that participation 85% were either unaware or unsure that participation

in clinical trials was an optionin clinical trials was an option 75% said they would have been willing to enroll had 75% said they would have been willing to enroll had

they known they known of the aware ones of clinical trial option, most of the aware ones of clinical trial option, most

declined to participate because of common myths declined to participate because of common myths about clinical trials:about clinical trials:

The medical treatment they would receive in a clinical trial The medical treatment they would receive in a clinical trial would be less effective than standard carewould be less effective than standard care

They might get a placeboThey might get a placebo They would be treated like a "guinea pig"They would be treated like a "guinea pig" Their insurance company would not cover costsTheir insurance company would not cover costs

Source:Source: www.harrisinteractive.com/harris_poll/www.harrisinteractive.com/harris_poll/

A Survey on Clinical Trial A Survey on Clinical Trial BarriersBarriers

People who received treatment through a People who received treatment through a clinical trial found it to be a very positive clinical trial found it to be a very positive experience:experience: 97% said they were treated with dignity and 97% said they were treated with dignity and

respect and that the quality of care they respect and that the quality of care they received was "excellent" or "good"received was "excellent" or "good"

Eighty-six percent said their treatment was Eighty-six percent said their treatment was covered by insurancecovered by insurance

Source:Source: www.harrisinteractive.com/harris_poll/www.harrisinteractive.com/harris_poll/

Barriers & PromotersBarriers & Promoters Barriers mainly 3 typesBarriers mainly 3 types

barriers to opportunity to participate (most)barriers to opportunity to participate (most) barriers to awareness or acceptance of barriers to awareness or acceptance of

clinical trialsclinical trials cultural factorscultural factors

Promoters mainly 3 typesPromoters mainly 3 types awarenessawareness transporttransport altruismaltruism

General Recruitment General Recruitment IssuesIssues

Cancer trials require years to complete, and Cancer trials require years to complete, and subject recruitment and enrollment can be a subject recruitment and enrollment can be a lengthy processlengthy process

Planning and pilot testing of recruitment Planning and pilot testing of recruitment methodsmethods

Monitoring of patient accrual with respect to a Monitoring of patient accrual with respect to a priori targetspriori targets

Regular feedback of recruitment progress to Regular feedback of recruitment progress to recruiting centresrecruiting centres

Development of a risk management plan to Development of a risk management plan to respond to failure to achieve targets respond to failure to achieve targets

Methodology to Particular Methodology to Particular Study Recruitment Issues Study Recruitment Issues

and Solutionsand Solutions Identify patient recruitment barriers through an Identify patient recruitment barriers through an

extensive review of the factors that hinder extensive review of the factors that hinder recruitment and retention recruitment and retention eg. complicated protocols, over-rigorous inclusion and eg. complicated protocols, over-rigorous inclusion and

exclusion criteria, etc.exclusion criteria, etc.

Identify solutions that work Identify solutions that work illustrated by extensive review and numerous case histories illustrated by extensive review and numerous case histories

of strategies and tactics that have been shown to improve of strategies and tactics that have been shown to improve recruitment and retentionrecruitment and retention

Obtain a thorough understanding of the Obtain a thorough understanding of the circumstances in which advertising can still offer a circumstances in which advertising can still offer a highly cost-effective means to recruit patients and highly cost-effective means to recruit patients and improve the quality and quantity of patients enrolled.improve the quality and quantity of patients enrolled.

Methodology to Study Methodology to Study Recruitment Issues and Recruitment Issues and

SolutionsSolutions Get an in-depth look at the technological and Get an in-depth look at the technological and

other innovations introduced by CROs and IT other innovations introduced by CROs and IT companiescompanies management of clinical trials generally and management of clinical trials generally and

recruitment and retention more specificallyrecruitment and retention more specifically Understand why a growing number of clinical Understand why a growing number of clinical

trials are performed in countries like Indiatrials are performed in countries like India cost benefitscost benefits large populationslarge populations pharmacogenetic profilingpharmacogenetic profiling issues that sponsors to considerissues that sponsors to consider

Gain reliable and thought-provoking insights Gain reliable and thought-provoking insights into key factors influencing patient recruitmentinto key factors influencing patient recruitment

Main Barriers to Main Barriers to RecruitmentRecruitment

Patient age Patient age ComorbidityComorbidity Disease stageDisease stage Mistrust of research method and researchersMistrust of research method and researchers Lack of physician/care giver awareness about Lack of physician/care giver awareness about

trialstrials CommunicationCommunication Method of IC presentation Method of IC presentation Community based approach versus Institution Community based approach versus Institution

based approachbased approach

Recruitment StrategiesRecruitment Strategies Hospitals, specialized hospitalsHospitals, specialized hospitals The use of occupational and targeted The use of occupational and targeted

screeningscreening Registers of trialsRegisters of trials Clinicians Clinicians Mass mediaMass media Direct mailing to access patientsDirect mailing to access patients Specialized interventionsSpecialized interventions Community campsCommunity camps

Barriers for Health Care Barriers for Health Care ProfessionalsProfessionals

Lack of awareness of appropriate clinical trials physicians are not always aware of available clinical

trials, local resources some may assume that none would be appropriate for

their patients Unwillingness to "lose control" of a person's care

relationship with patients is very important doctors fear they may lose control of the person's care

Belief that standard therapy is best Belief that referring and/or participating in a

clinical trial adds an administrative burden Concerns about the person's care or how the

person will react to the suggestion of clinical trial participation

Specific BarriersSpecific Barriers Long-standing fear, apprehension, and skepticism Doctors may not mention clinical trials as an option

for cancer care. People from various cultural or ethnic backgrounds

hold different values and beliefs that may be different than principles of Western medicine.

Language or literacy barriers may make it difficult for some people to understand and consider participating.

Additional access problems confront many people

Cost BarriersCost Barriers The costs associated with clinical trials can be a The costs associated with clinical trials can be a

barrier for many professionals and the publicbarrier for many professionals and the public Physicians are often concerned about Physicians are often concerned about

reimbursement related to the expense of either reimbursement related to the expense of either caring for people enrolled in trials or offering caring for people enrolled in trials or offering trials within their practicetrials within their practice

Potential trial participants often fear that their Potential trial participants often fear that their insurance company will not cover participationinsurance company will not cover participation

Those who are uninsured will need to know Those who are uninsured will need to know how their participation in a trial will be how their participation in a trial will be covered.covered.

Differences Between Differences Between Passive and Active Passive and Active

RecruitmentRecruitment Patients were employeesPatients were employees In the passive employee contact armIn the passive employee contact arm

employees were contacted from a list of employee employees were contacted from a list of employee names and telephone numbers provided by the names and telephone numbers provided by the companycompany

In the active employee contact armIn the active employee contact arm employees actively signed up to participateemployees actively signed up to participate

While lower enrollment and higher attrition were While lower enrollment and higher attrition were observed in the passive recruitment arm, the passive observed in the passive recruitment arm, the passive method enrolled a more diverse group of participants method enrolled a more diverse group of participants than did the active recruitment methodthan did the active recruitment method

Source: Linnan LA et al Source: Linnan LA et al Ann Behav MedAnn Behav Med 2002;24(2):157-66 2002;24(2):157-66

Effect of an Intervention Effect of an Intervention ProgramProgram

Intervention program consisted of the installation Intervention program consisted of the installation of a rapid tumor-reporting system of a rapid tumor-reporting system to improve data quality and to expedite the receipt of to improve data quality and to expedite the receipt of

information on cancer patients from physiciansinformation on cancer patients from physicians a nurse facilitator who would notify physicians of clinical a nurse facilitator who would notify physicians of clinical

trialstrials a quarterly newsletter mailed to physicians about cancer a quarterly newsletter mailed to physicians about cancer

treatment and clinical trialstreatment and clinical trials a health educator who trained lay health educators and a health educator who trained lay health educators and

provided community-based information about cancer provided community-based information about cancer screening, treatment, and clinical trialsscreening, treatment, and clinical trials

The rates of enrollment into clinical treatment The rates of enrollment into clinical treatment trials did not improve significantly in the trials did not improve significantly in the intervention communitiesintervention communities

Source:Ford Met al Source:Ford Met al Clinical TrialsClinical Trials 2004;1:343-51 2004;1:343-51

Successful RecruitmentSuccessful Recruitment Detailed understanding of the stages in the Detailed understanding of the stages in the

recruitment processrecruitment process Identification of steps where potential patients are Identification of steps where potential patients are

lost lost Development of alternative tactics to enhance Development of alternative tactics to enhance

recruitment.recruitment. Timeliness & cost containmentTimeliness & cost containment Ability to detect subtle treatment effects Ability to detect subtle treatment effects Meeting ethical responsibilities to patients and Meeting ethical responsibilities to patients and

cliniciansclinicians Employment of an enthusiastic, committed and Employment of an enthusiastic, committed and

talented stafftalented staff Initiative and adaptability to recruitment problemsInitiative and adaptability to recruitment problems

Successful RecruitmentSuccessful Recruitment Invitation of keen and successful investigators Invitation of keen and successful investigators Development of a comprehensive investigator's Development of a comprehensive investigator's

manual manual Organising investigator recruitment meetings Organising investigator recruitment meetings Provision of numerous study aids to the centres Provision of numerous study aids to the centres Maintaining contact with the centres via the Maintaining contact with the centres via the

telephone telephone Regular monitoring of recruitment progress and Regular monitoring of recruitment progress and

strategies (with subsequent feedback to the strategies (with subsequent feedback to the centres via the study newsletter and meetings for centres via the study newsletter and meetings for both the investigators and study nurses). both the investigators and study nurses).

Strategies for Successful Strategies for Successful RecruitmentRecruitment

(Hospitalized Patients) (Hospitalized Patients) Provide checklists on patient charts with Provide checklists on patient charts with

eligibility criteriaeligibility criteria Placing posters with open protocols listedPlacing posters with open protocols listed Using abridged "protocol pocket cards" with key Using abridged "protocol pocket cards" with key

inclusion and exclusion criteriainclusion and exclusion criteria Dedicate one research nurse or research Dedicate one research nurse or research

assistantassistant to identifying and screening participantsto identifying and screening participants coordinating pre-enrollment testscoordinating pre-enrollment tests educating participants about the protocol and processeducating participants about the protocol and process and initiating the informed consent and enrollment and initiating the informed consent and enrollment

processprocess Access funding for clinical trial supportAccess funding for clinical trial support

Successful RecruitmentSuccessful Recruitment One particular studyOne particular study

the study nurse being employed for longer hours the study nurse being employed for longer hours ((PP<0.001)<0.001)

the use of a coronary care register to identify the use of a coronary care register to identify eligible patients (eligible patients (PP=0.001)=0.001)

a systematic recruitment plan with targets and a systematic recruitment plan with targets and timetable (timetable (PP=0.02)=0.02)

the invitation of patients by both a personal letter the invitation of patients by both a personal letter and follow-up phone call (P=0.09)and follow-up phone call (P=0.09)

regular contact with the patients' usual doctors regular contact with the patients' usual doctors and adequate funding of centres and adequate funding of centres

Source: Source: NHMRC Clinical Trials Centre, University of Sydney, Sydney, AustraliaNHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia

Another Study: Recruitment Another Study: Recruitment Facilitation FactorsFacilitation Factors

Interest in the research question, participation did not Interest in the research question, participation did not require any unusual management practicesrequire any unusual management practices

Toll-free telephone randomisation and a simple one-Toll-free telephone randomisation and a simple one-page outcome form each took only a few minutes to page outcome form each took only a few minutes to complete complete

Well-organised and committed principal nursesWell-organised and committed principal nurses Ongoing staff trainingOngoing staff training Investigators’ meetingsInvestigators’ meetings Regular communication and target settingRegular communication and target setting BarrierBarrier

minimal financial recompense for staff timeminimal financial recompense for staff time many potentially eligible patients could not be recruited because of the many potentially eligible patients could not be recruited because of the

lack of staff time to dedicate to research lack of staff time to dedicate to research

Source: Source: Clinical Trials Research Unit, University of Auckland, Auckland, New ZealandClinical Trials Research Unit, University of Auckland, Auckland, New Zealand

Three Critical IssuesThree Critical Issues Risk to participantsRisk to participants

Practicality of Periodic Review of a Practicality of Periodic Review of a TrialTrial

Scientific Validity of the TrialScientific Validity of the Trial

Risk to ParticipantsRisk to Participants The study endpoint is such that a highly favorable or unfavorable

result, or even a finding of futility, at an interim analysis might ethically require termination of the study before its planned completion

There are a priori reasons for a particular safety concern, as, for example, if the procedure for administering the treatment is particularly invasive

There is prior information suggesting the possibility of serious toxicity with the study treatment

The study is being performed in a potentially fragile population such as children, pregnant women or the very elderly, or other vulnerable populations, such as those who are terminally ill or of diminished mental capacity

The study is being performed in a population at elevated risk of death or other serious outcomes, even when the study objective addresses a lesser endpoint

The study is large, of long duration, and multi-center

Practicality of a DMCPracticality of a DMC If the trial is likely to be completed

quickly, the DMC may not have an opportunity to have a meaningful impact

In short-term trials with important safety concerns, however, a DMC may still be valuable

Scientific Validity of the Scientific Validity of the TrialTrial

Recommendations to change inclusion criteria the trial endpoints or the size of the trial

Scientific validity best evaluated by an unbiased oversight committee with the exception of changes the Committee

might recommend on the basis of emerging safety concerns

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