clinical trial recruitment strategy

Developing an effective recruitment strategy

Riccardo Belli, MD

Email contact: [email protected]

A warning

Opinion expressed in this presentation are those of the

Author and not necessarily those of the representative

Company

Subject recruitment importance

86% of all clinical trials fail to recruit the required number of

subjects on time with 52% delayed by one to six months 1

clinical trials last 42% longer than expected in Phase I, 31%

longer in Phase II, and 30% beyond planned deadlines in

Phase III—all because of recruitment delays 2

85%–95% of all days lost during clinical trials are due to a

failure to recruit subjects on time 3

Each day a drug is delayed from market, sponsors lose up

to $8 million 3

1. Mary Jo Lamberti ―Enrollment Delays are Getting Worse,‖ in An Industry in Evolution, 4th ed., Ed. (Thomson

CenterWatch, Boston, 2003), 79.

2. Cutting Edge Information, "Accelerating Clinical Trials: Budgets, Patient Recruitment, and Productivity," May 2004

3. J. Cruz Rowe, M.E. Elling, J.G. Hazlewood, R. Zakhary, ―A Cure for Clinical Trials,‖ The McKinsey Quarterly, (2) 134–

141 (2002).

Critical key player in the recruitment process

Investigators

Subjects

Protocol

Environment

Investigators Importance on recruitment process

They add credibility and medical expertise in the clinical

area and mediate the study discussion

They have access to information pertaining to subjects

whose characteristics are more appropriate to the study

conducted

They have daily exposure to potential subjects and are able

to introduce information about the trial and ask for their

participation during these visits.

InvestigatorsAspects with negative impact on recruitment 1,2

Logistical aspects

– Lack of time (workload)

– Lack of resources and training

– Unstable research team

– Overestimation of the available study population

Personal aspects

– Concern for the patients

– A lack of interest in the research question

– Concern for the effect on the investigator–patient relationship

– Concern for potential loss of clinical autonomy

– An inability to deal with conflicting roles

1. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial

http://www.harrisinteractive.com./news2001Vol1_iss3.pdf

2. J. Sullivan, "Subject Recruitment and Retention: Barriers to Success," Applied Clinical Trials, 14 (4) (April 2004).

InvestigatorsAspects with positive impact on recruitment 1,2,3

Personal aspects

– Scientific interest

– Patient benefits

• Dissatisfaction with current therapies

• Desire to provide leading-edge care to their patients

• Providing access to treatment, tests, and services that are not

reimbursed or available

– Scientific immediacy

• Regular communication about results and recruitment status

– Financial compensation

– Relationship with the Sponsor and CRO




3. Jefferies & Company, Contract Research Industry Comprehensive Update: Can CROs Outperform Their Customers

Again? Pharmaceutical Services Quarterly Preview, January 19, 2005

InvestigatorsStrategy to improve recruitment aspects

Investigator and Site selection

Investigator and Site performance

Communication between Investigator and the Sponsor


Adequate sources information

– Company and Affiliates colleagues feedback

– Refferral Investigator feedback

– Library Database (eg. Pubmed, Scopus)

– Intelligence service (eg. SiteTrove, TrialTrove)

– Clinical trial Register Database (eg. international and national

database clinical trial registry)

– Qualified CRO feedback

– Professional Network


Proved scientific interest in related field (eg. pediatric

infection disease treatment and prevention)

Previous attested experience in clinical trial sponsored by

pharmaceutical company

Access and estimation to the appropriate subject population

– Evaluate previous recruitment performance with similar population

– Understanding the frequency with which investigator see the desired

subjects

– Provide a realistic recruitment plan

– Provide a detailed subject source mapping


Adequate resources and training

– Adequate staff and facilities for recruitment potential

Compliance with GCP and applicable regulatory

requirement

– Previous internal audit

– Previous inspection from Competent Authority

– Feedback from national or international Clinical Investigator

Inspection List

EC approval and contract finalization achived in a

reasonable timeframe


Costant monitoring of adequate resources presence and

training during the trial

– Estimate study staff turnover

– Guarantee a costant training and monitoring the site before and

during the trial

Management of the site workload

– Limit at the ―essential‖ the complexity of the study process

– Site could hire for a temporary period a ―clinical site coordinator‖ to

support data entry and recruitment


Promote the investigator scientific interest

– Involve the investigator in the protocol procedure development and

country study feasibility process

– Collaborate with Medical Affair in the way to make the investigator

clinical activity ―evident‖

Optimize financial compensation

– Have a current overview about the fees applied by other companies

in certain area

– Establish the best fee according to the protocol complexity and staff

workload (es. EDC, number of visits, blood drawn)


Involve the investigator in the study information loop

– Costant comunication with the investigators about the study

performance and analisys results

– PeriodicaIly inform all the study investigators about the recruitment

status by site and by country in the way to aliment a ―positive

competitive‖ recruitment environment

– Promote an investigator expert networking

Optimize the recruitment process

– Collaborate with the investigator for the creation of a detailed and

realistic site recruitment procedure plan

– Define a correct communication plan

– Include the recruitment in the risk management plan process


Define a correct ―Information Flow‖

– Define each role and the responsability at site study staff and

Sponsor level (es. define staff accountable for recruitment)

– The Sponsor should establish strong communication with the

reference study staff involved in the enrollment process, in order to

expedite decisions and the recruitment progress between the

Sponsor and recruitment consultants

– Periodic teleconference to discuss performance versus recruitment

plan

Subjects Importance on recruitment process

Pivotal role as the most important ―partner‖ in the clinical

research process

Subjects Aspects with negative impact on recruitment 1,2

Logistic and economic aspects

– Travel distance

– Travel costs

– Cost not covered by insurance (eg. in US)

Demographic aspects

– Age

– Level of education

– Language

– Cultural issue

– Social circumstances (lack time to attend extra trial-related

appointments due to family commitments)

– Attitude of family members (elderly may be reluctant to participate in

a clinical trial due to family objections )1. Missconception and lack of awareness greately reduce recruitment for cancer clinical trial




Subjects attitude to the clinical trial

– Uncertainty of the therapy

– Lack of information about clinical trial benefit

– ―Guinea Pig‖ syndrome

– The additional demands associated with trial participation

– Effort involved in informed consent process

Subjects attitude to the trial design

– Treatment schedule

– Study timing (visit numbers and timing windows, partecipation

period)

– Fear placebo rather than active treatment





Disease related aspects

– Subjects disease status

Personal dinamic of the subject

– Subjects tending to change jobs more frequently and are moving to

new locations to take up these jobs




Subjects Aspects with positive impact on recruitment 1

Positive experience reported by subjects in clinical trials

– High rate of quality care

– Obtain faster access to treatment

– Dignity and respect

– Not subjected to more tests and procedures than they thought

necessary

– Not treated like ―Guinea Pig‖

– subjects who participated in clinical studies would do so again

Most of public believe it is ―essential‖ or ―very important‖ that

all new pharmaceutical products be tested on humans

before they are approved for general use



Strategy to improve Subjects related recruitment aspects

Good comunication skills

Site facilities and procedure

Logistic support


Subjects need to be informed and understand what

partecipation in clinical trial can potentially offer them and

help to turn those who are ―somewhat confident‖ into ―very

confident‖

– How their clinical trials is designed (goal and requirements)

– What is hoped to be gained by their partecipation

– Informed of the risk and benefit

– Protection available for them as subjects regarding costs, privacy

and right

Such reassurance is hindered by the fact that so few protocol

developers are able to write consent documents that comply with the

directive in 21 CFR 50.20 thus ―Putting technical medical terms into

easily understood language is a rare art form‖


Site Staff good comunication skills

– Site staff who will be screening and interviewing potential subjects

and obtaining informed consent skilled at verbal communications

and responding to subjects’ questions and concerns

• Organize site staff training providing also informative material (eg.

Distribute FAQ from site and subjects)

– Site staff focused on creating a pleasant ―customer service‖

experience for the subject

• Spending time talking and listening, offering information, and giving

subjects time to express their experiences and ask questions

• Welcoming subjects, valuing their experience, responding to their

suggestions and respecting subjects as partners in the clinical research

process


Sponsor good comunication skills

– Organize ad hoc training session with expert to further improve

comunication skills

– Working together with site staff could contribute to further improve

the readibility of the informed consent and other documents in

simple language and structure

– Provide written educational materials to read and resources about

the informed consent process as well as specifics about the study

– Expressing appreciation for volunteer time and commitment helps

reinforce the participants’ experience of contributing to science and

increases their trust in the clinical research enterprise


Site facilities and procedure to be in compliance with

subjects expectations (to be check during pre-study visits)

– Subject-friendly facilities

• Comfortable waiting room

• General appearance (e.g. surroundings, atmosphere, parking, arrival)

– Efficient appointment scheduling

– Adaptation of clinic staff to accommodate subjects’ work schedules

– Type of screening procedures (clinical chart review, phone, mail,

face to face)

Logistic support

Cover subject expenses

– Travel cost support

Protocol Aspects with negative impact on recruitment

The Study design

Data collection requirements

Inclusion and exclusion criteria

Incompatibility of the protocol procedures with usual clinical

practice

Disagreement with the protocol by some investigators

An investigator’s lack of full support and enthusiasm for an

aspect of the study


Sponsor strategy to improve protocol related recruitment aspect

Obtain secure input from the sites on protocol and study

related documents (eg. diary card, worksheet) and

procedure

– Made the protocol as an ―opportunity‖ for the subject

• Guarantee the best supportive care and treatment according to the

local requirement

• Evaluate a protocol strategy to overcome weakness related to placebo

– Inclusion and exclusion criteria

• Compliance with the disease or condition being studied

– Concomitant medication

• Compliance with the local schedule and requirements

– Medical procedure and treatments

• Compliance with the standard medical practice

– Visit schedule

• Compliance in terms of visit frequency and duration

Environment Aspects with negative impact on recruitment

Although the subjects population in general may be the

same age and be suffering from the same conditions as

required by the study, each potential subject is unique in

terms of his or her interests, needs, motivations, and habits

and is part of a particular cultural environment

Each site is structured differently, operates in different

environments, personnel and needs

1. Lars-Olof Eriksson , Beth D. Harper,‖ Successful Subject Recruitment: One Size Does Not Fit All‖, Applied Clinical

Trials 14 (1) November 1, 2002

Strategy to improve environmental related recruitment aspects

Elaborate ―ad hoc‖ risk analisys taking in consideration the

whole local environmental aspects

– Organize specific feasibility assessment at country/district level

involving internal and external stakeholder with previous experience

in the area

• Company and Affiliates colleagues

• CRO

• Referral investigators

Conclusion

Selecting the most appropriate and cost-effective approach to reaching potential subject populations is complex and multifaceted

Establish a good comunication between subjects, investigators and Sponsor is important for improving the recruitment process

Understanding and avoiding common mismatches between the protocol design, site infrastructure, and prospective subjects’ interests and needs will make recruitment easier

Successful recruitment requires sensitivity to site, geographic, cultural, and community differences and a willingness to tailor the recruitment program, where possible, to accommodate these differences

clinical trial recruitment strategy

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