A basic fact about clinical research is:
“even though a study may be very well
designed and well funded, it cannot bring a
drug to market without the availability of
Patient recruitment and retention in clinical
trials is recognized as the “key bottleneck” in
the new drug development pipeline.
The process of new drug development is
extremely time consuming and expensive.
Recruitment of appropriate subjects takes up
30% of clinical timelines and so it is an issue
that must be considered before and
throughout the duration of the study.
Internationally, recruitment and retention of
patients are a big challenge.
More than 80% of global trials fail to enroll on
time with 52% delayed by 1-6 months.
Failure to recruit patients on time leads to loss
of over 85-95% of days in a clinical trial.
It is a leading cause of missed clinical trial
The number of patients required to undergo
clinical trials for a new drug is steadily
Presently 5300 (approx.) subjects are needed
per NDA and 80000 clinical trials are
underway in the US alone.
So, sponsors are scrutinizing recruitment
plans before entrusting a clinical trial to a
India is attracting global attention in this field
due to the availability of a large and essentially
treatment-naïve patient pool.
Other advantages include: low costs,
satisfactory medical infrastructure and
However, most trials in India take place at a
few well known urban hospitals.
As the number of clinical trials in India
increase, similar challenges in recruitment
Difficulties in Recruitment
Recruitment strategies are rarely considered early
Inclusion/exclusion criteria are narrowly defined.
Budgets allocated for effective recruitment are
Enrollment deadlines are not realistic.
Investigator may lack a basic knowledge about
Investigator may assume that he will rely on his own
database for recruitment which may be inadequate.
Negative publicity from the media (highlights failures
and underplays advantages).
Basic Principles of Patient
Why do patients join clinical trials?
Wanting to help advance knowledge of disease in the
interest of society. Besides a few altruistic
individuals the main reasons for participating
includes - lack of availability therapy, improved
medical care, lack of health insurance, advise from
the family physician & due to financial reasons.
Barriers to participationBarriers to participation
A/c to Harris interactive survey reported that
71% of eligible patients choose not to participate
in clinical trials.
Reasons for not participating could be:
Risk of side – effects
Center too far away
Unable to find a trial (unawareness)
Not enough / Insufficient information.
what motivates the patient towhat motivates the patient to
participate in a clinical trial?participate in a clinical trial?
Access to greater medical expertise
Access to Promising therapies
Closed individualized medical care
Something to do (break boredom)
Ethical issues in patient
Confidentiality and privacy of personal health
information- As a part of the recruitment
process an investigator has access to a
patient’s health information. In the USA, this
health information is protected by a federal law
called HIPAA, i.e. the Health Insurance
Portability and Accountability Act.
Advertising for Clinical Trial Patients-
Advertising is one of the ways of recruiting
protocol suitable patients in clinical trials.
There are guidelines laid down by ICH GCP,
Indian GCP and clinical trial regulations of
respective countries on the use of advertising
for subject recruitment in clinical trials. All the
advertising material proposed to be used for
subject recruitment in a clinical trial must be
submitted to the IRB/IEC for review and
approval before it can be used.
Undue influence- Offering excessive,
unwarranted, inappropriate or improper
compensation as an attraction to enroll or
remain compliant in a clinical trial is called
using undue influence, e.g. Rs. 4,000 for a 4-
day, treatment of common cold. To prevent
undue influence compensation must be
reasonable and must not influence a patient’s
decision to enroll in a trial.
Vulnerable population- Patient who cannot be
expected to choose what is right for
themselves, i.e. those who have limitations on
their capacity or freedom is termed a
For these vulnerable groups the informed
consent from may be signed by a legally
acceptable representative ,the patient’s
“assent” is very important. Every effort must
be made to explain the study to the subject up
to the level of his understanding.
METHODS OF PATIENT
To get appropriate subjects within the
specified time frame :
1. Investigators database:
Investigators site chosen because of expertise in particular
Investigators generally tend to overestimate the no. of patients he
would be able to enroll as he tend to look for overall diagnosis
without weighing the exclusion criteria.
2. Clinician Referrals:
For pre study promotions, presentations, meetings and forums are
Clinicians are made aware of eligibility criteria and recruitment
Recruitment material- posters, flyers, mail shots, which clinician
can send to subjects
Material should be approved by IEC and letters should have “Opt –
Mass media campaigns – newspaper advertisements, radio or TV
advertisements, press releases, mailings billboards, public
All approved by IEC before used
Advertisements should follow a criteria:
Should not be misleading
No claims for safety/ efficacy/ superiority
No terms as ‘new treatment’ / ‘new drug’ without explaining
that the test article is investigational
Advertisements should not promise ‘free medical treatment’
when intent is not to charge the subjects
Key elements of Advertisements:
Name of the research facility
Purpose of research and Eligibility criteria(Briefly stated)
Contact person for more info
The word “research”
If monetary compensation is offered, it must not be presented as an
inducement to participate
4. Community based:
Recruitment through organizing health camps which will target the
populations having the disease under study
Speaking at a meeting for disease specific support group would
5. Web based:
Companies listing clinical trails on web. centrewatch.com and clinical
Online partnerships with search engines yahoo and Google enable
sponsors to provide lead to subjects
Web sites are used to post the pre qualifying questionnaire and to pre
screen subjects online through a secure network setup.
6. Call centers:
They form the first point of contact for a patient in the recruitment
process and health information data is obtained through telephone
screen. Data can be rapidly processed and filtered to spread
recruitment to several sites
Call centers can help by giving first appointment to patient at a
Recruitment success is to be measured and accountability is designed:
complete tracking of each point of contact
pre screening call
scheduling of first screening visit
linking these actions to referral source
Prior to starting recruitment campaign, an investigators needs to project how
many patients he would need in order to get ‘n’ no. of patients for screening
and what percentage of that the would ultimately be able to enroll for a
Patients identified 1000
End of prescreening 400
End of screening(incl/exl) 250
Qualified/ evaluable 100
From previous studies:
Average only 1 in 20 patients who responds to recruitment promotion ever
complete the study and 1 out of 5 who respond ever show up for initial
Steps in the recruitment
There are following steps involved in patient
Identification of patient
Informed Consent and Screen
Enrollment of patient
Identification of patient
Suitable for study protocol
Risk and benefits
Patient information sheet
Sign the informed consent
Informed consent and screen
Sign by patient
Undergoes for Screening
Professional Approach to
Properplanning at initial stages of protocol design to make it easy
for investigator to recruit patients.
Budgeting for patient recruitment must start in early planning
stages so that expenses can be anticipated, allocated & contained.
Trends toward centralized budgeting so that sponsor had a control
over recruitment expenditure.
Monitoring of all recruitment activities for their effectiveness.
Recruitment metrics: evaluate the effectiveness of a recruitment
program, measures & analyze the success of various recruitment
Helps to identify strategies that are not working so that modification
& remedial measures may be undertaken to salvage enrollment
Training: for recruitment & retention occur at 2 stages:
is where the sponsor trains the investigator sites in pt.
recruitment methodology & for centralized recruitment initiatives.
level of training occurs at the investigator site, which ensures
that the site staff understands the protocol & procedures, and
agrees with the recruitment initiatives.
This is to allow the staff to be more proactive throughout
recruitment & retention.
Retention of SubjectsRetention of Subjects
Keeping subjects in the studyKeeping subjects in the study
Retention is closely linked to satisfactionRetention is closely linked to satisfaction
• Consent signingConsent signing
• Treating participants with respectTreating participants with respect
• Communication between research staffCommunication between research staff
• Communication about disease processCommunication about disease process
• Attention to factors such as transportation etc.Attention to factors such as transportation etc.
Reasons why volunteers drop outReasons why volunteers drop out
Drop outs can be less than 10%Drop outs can be less than 10%
• Adverse effectAdverse effect
• Lack of BenefitLack of Benefit
• Other medical problemOther medical problem
• Lack of transportationLack of transportation
Methods to retain subjectsMethods to retain subjects
Communication: Explain up front that all data isCommunication: Explain up front that all data is
Explain that placebo groups receive treatmentExplain that placebo groups receive treatment
Protocol is reasonableProtocol is reasonable
Bonuses at key time pointsBonuses at key time points
Avoid large gaps between study contactsAvoid large gaps between study contacts
Costs of transportationCosts of transportation
Encourage patients to stay in study even if theyEncourage patients to stay in study even if they
stop treatmentstop treatment
Methods to Enhance RetentionMethods to Enhance Retention
Communication with StaffCommunication with Staff
Offer convenient appointment timesOffer convenient appointment times
Send newsletterSend newsletter
Provide written or telephone contacts betweenProvide written or telephone contacts between
Remember special occasionsRemember special occasions
Assist with transportationAssist with transportation
Financial compensationFinancial compensation
Professional Recruitment providers:
Professional recruitment providers today
often work with sponsor ,CROs and
SMOs to improve recruitment efforts at a
Increased use of market
Use of MR strategies to inc. patient
recruitment through sponsors.
MR include demography(age, gender and
education level),geography(urban , rural
,state) , psychology(attitude , lifestyle)and
Approach to find good potential subjects.
Provide de-identified data obtained from
pharmacies , physicians , hospitals , insurance
Once the population is defined an informatics
service provider would target it with a direct mail
It is the centralized location for all information
regarding potential participants.
Most suitable candidates are scheduled at the
various research sites.
Facilitates accurate tracking and analysis of
Development of metrics - the leaky
Identifies the effectiveness recruitment
Leaky – pipe analysis is visual aid ;once
identified, the leaky areas of the pipeline need
to be repaired.
Not only helps in recruitment process but also
helps to repair when damages are done.
As the number of clinical trial increases , the
number of patients needed for clinical trial
continues to increase.
Thus , recruitment of subjects today has become a
partnering process between the sponsor and an