Recruitment in Cancer Trials Dr. Bhaswat S. Chakraborty VP, R & D, Cadila
Patient Participation in Cancer Trials A 1999 press release from the American Society of Clinical Oncologists only 3% of adults with cancer participate in clinical trials far fewer than the number needed to answer the most pressing cancer questions quickly Up to 80% of clinical trials are estimated to experience problems with recruitment
A Survey on Clinical Trial Barriers A survey of almost 6,000 people with cancer conducted in 2000 85% were either unaware or unsure that participation in clinical trials was an option 75% said they would have been willing to enroll had they known of the aware ones of clinical trial option, most declined to participate because of common myths about clinical trials: The medical treatment they would receive in a clinical trial would be less effective than standard care They might get a placebo They would be treated like a "guinea pig" Their insurance company would not cover costs Source: www.harrisinteractive.com/harris_poll/
A Survey on Clinical Trial Barriers People who received treatment through a clinical trial found it to be a very positive experience: 97% said they were treated with dignity and respect and that the quality of care they received was "excellent" or "good" Eighty-six percent said their treatment was covered by insurance Source: www.harrisinteractive.com/harris_poll/
Barriers & Promoters Barriers mainly 3 types barriers to opportunity to participate (most) barriers to awareness or acceptance of clinical trials cultural factors Promoters mainly 3 types awareness transport altruism
General Recruitment Issues Cancer trials require years to complete, and subject recruitment and enrollment can be a lengthy process Planning and pilot testing of recruitment methods Monitoring of patient accrual with respect to a priori targets Regular feedback of recruitment progress to recruiting centres Development of a risk management plan to respond to failure to achieve targets
Methodology to Particular Study Recruitment Issues and Solutions Identify patient recruitment barriers through an extensive review of the factors that hinder recruitment and retention eg. complicated protocols, over-rigorous inclusion and exclusion criteria, etc. Identify solutions that work illustrated by extensive review and numerous case histories of strategies and tactics that have been shown to improve recruitment and retention Obtain a thorough understanding of the circumstances in which advertising can still offer a highly cost-effective means to recruit patients and improve the quality and quantity of patients enrolled.
Methodology to Study Recruitment Issues and Solutions Get an in-depth look at the technological and other innovations introduced by CROs and IT companies management of clinical trials generally and recruitment and retention more specifically Understand why a growing number of clinical trials are performed in countries like India cost benefits large populations pharmacogenetic profiling issues that sponsors to consider Gain reliable and thought-provoking insights into key factors influencing patient recruitment
Main Barriers to Recruitment Patient age Comorbidity Disease stage Mistrust of research method and researchers Lack of physician/care giver awareness about trials Communication Method of IC presentation Community based approach versus Institution based approach
Recruitment Strategies Hospitals, specialized hospitals The use of occupational and targeted screening Registers of trials Clinicians Mass media Direct mailing to access patients Specialized interventions Community camps
Barriers for Health Care Professionals 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 persons care relationship with patients is very important doctors fear they may lose control of the persons care Belief that standard therapy is best Belief that referring and/or participating in a clinical trial adds an administrative burden Concerns about the persons care or how the person will react to the suggestion of clinical trial participation
Specific 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 Barriers The costs associated with clinical trials can be a barrier for many professionals and the public Physicians are often concerned about reimbursement related to the expense of either caring for people enrolled in trials or offering trials within their practice Potential trial participants often fear that their insurance company will not cover participation Those who are uninsured will need to know how their participation in a trial will be covered.
Differences Between Passive and Active Recruitment Patients were employees In the passive employee contact arm employees were contacted from a list of employee names and telephone numbers provided by the company In the active employee contact arm employees actively signed up to participate While lower enrollment and higher attrition were observed in the passive recruitment arm, the passive method enrolled a more diverse group of participants than did the active recruitment method Source: Linnan LA et al Ann Behav Med 2002;24(2):157-66
Effect of an Intervention Program Intervention program consisted of the installation of a rapid tumor-reporting system to improve data quality and to expedite the receipt of information on cancer patients from physicians a nurse facilitator who would notify physicians of clinical trials a quarterly newsletter mailed to physicians about cancer treatment and clinical trials a health educator who trained lay health educators and provided community-based information about cancer screening, treatment, and clinical trials The rates of enrollment into clinical treatment trials did not improve significantly in the intervention communities Source:Ford Met al Clinical Trials 2004;1:343-51
Successful Recruitment Detailed understanding of the stages in the recruitment process Identification of steps where potential patients are lost Development of alternative tactics to enhance recruitment. Timeliness & cost containment Ability to detect subtle treatment effects Meeting ethical responsibilities to patients and clinicians Employment of an enthusiastic, committed and talented staff Initiative and adaptability to recruitment problems
Successful Recruitment Invitation of keen and successful investigators Development of a comprehensive investigators manual Organising investigator recruitment meetings Provision of numerous study aids to the centres Maintaining contact with the centres via the telephone Regular monitoring of recruitment progress and strategies (with subsequent feedback to the centres via the study newsletter and meetings for both the investigators and study nurses).
Strategies for Successful Recruitment (Hospitalized Patients) Provide checklists on patient charts with eligibility criteria Placing posters with open protocols listed Using abridged "protocol pocket cards" with key inclusion and exclusion criteria Dedicate one research nurse or research assistant to identifying and screening participants coordinating pre-enrollment tests educating participants about the protocol and process and initiating the informed consent and enrollment process Access funding for clinical trial support
Successful Recruitment One particular study the study nurse being employed for longer hours (P<0.001) the use of a coronary care register to identify eligible patients (P=0.001) a systematic recruitment plan with targets and timetable (P=0.02) the invitation of patients by both a personal letter and follow- up phone call (P=0.09) regular contact with the patients usual doctors and adequate funding of centres Source: NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
Another Study: Recruitment Facilitation Factors Interest in the research question, participation did not require any unusual management practices Toll-free telephone randomisation and a simple one-page outcome form each took only a few minutes to complete Well-organised and committed principal nurses Ongoing staff training Investigators’ meetings Regular communication and target setting Barrier minimal financial recompense for staff time many potentially eligible patients could not be recruited because of the lack of staff time to dedicate to research Source: Clinical Trials Research Unit, University of Auckland, Auckland, New Zealand
Three Critical Issues Risk to participants Practicality of Periodic Review of a Trial Scientific Validity of the Trial
Risk 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 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 Trial 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