PATIENT RECRUITMENT &

RETENTION IN CLINICAL TRIALS

By: PGDACR Batch (ICRI, Dehradun)

Introduction

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 suitable subjects”

Contd..

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.

Contd..

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 deadlines.

Background

The number of patients required to undergo clinical trials for a new drug is steadily increasing.

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 particular site.

Indian Scenario

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 scientific talent.

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 may occur.

Difficulties in Recruitment Process: Recruitment strategies are rarely considered early

enough. Inclusion/exclusion criteria are narrowly defined. Budgets allocated for effective recruitment are

inadequate. Enrollment deadlines are not realistic. Investigator may lack a basic knowledge about

recruiting patients. 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 Recruitment

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 Barriers to participationparticipation

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 what motivates the patient to participate in a clinical to participate in a clinical

trial?trial? Access to greater medical expertise

Access to Promising therapies

Closed individualized medical care

Something to do (break boredom)

Altruism.

Ethical issues in patient recruitment 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.

Cont…

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.

Cont….

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.

Cont…

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 vulnerable population.

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 RECRUITMENT To get appropriate subjects within

the specified time frame :

Recruitment strategy

Budget

Contd…

1. Investigators database: Investigators site chosen because of expertise in particular therapeutic

area 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

arranged Clinicians are made aware of eligibility criteria and recruitment

materials Recruitment material- posters, flyers, mail shots, which clinician can

send to subjects Material should be approved by IEC and letters should have “Opt –in” or

“Opt- out” option.

Contd…

3. Advertisement

Mass media campaigns – newspaper advertisements, radio or TV advertisements, press releases, mailings billboards, public announcements

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

Contd…

Key elements of Advertisements:

Name of the research facility Purpose of research and Eligibility criteria(Briefly stated) Time commitment 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 increase awareness

Contd..

5. Web based:

Companies listing clinical trails on web. centrewatch.com and clinical trails.gov

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 convenient centre

Limitations- training to operators, language specialists in multinational studies, confidentiality of data.

RECRUITMENT METRIX

Recruitment success is to be measured and accountability is designed:

Accountability includes- complete tracking of each point of contact pre screening call scheduling of first screening visit Recruitment enrollment Retention linking these actions to referral source

RECRUITMENT FUNNEL

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 particular study

Patients identified 1000 End of prescreening 400 End of screening(incl/exl) 250 Randomized 150 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 screening

Recruitment funnel is the basis of setting up budget for the trial

Steps in the recruitment process There are following steps involved in

patient recruitment:- Identification of patient Approach Informed Consent and Screen Assessment Enrollment of patient

Contd..

Identification of patient Suitable for study protocol By investigator Investigator’s Database Prescreening

Approach Risk and benefits Patient information sheet Sign the informed consent

Contd..

Informed consent and screen Sign by patient Undergoes for Screening

Assessment Lab report Suitability

Enrollment Inclusion/Exclusion criteria Randomization

Professional Approach to Recruitment Proper planning 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 methods.

Helps to identify strategies that are not working so that modification & remedial measures may be undertaken to salvage enrollment timelines.

Contd…

Training: for recruitment & retention occur at 2 stages: 1st is where the sponsor trains the investigator sites in pt.

recruitment methodology & for centralized recruitment initiatives.

2nd 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 signing Consent 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 out Reasons 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

• TimeTime

Methods to retain subjects Methods to retain subjects

Communication: Explain up front that all data is Communication: Explain up front that all data is

importantimportant

Explain that placebo groups receive treatment Explain 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 transportation Costs of transportation

Encourage patients to stay in study even if they Encourage 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 between Provide written or telephone contacts between

visitsvisits

Remember special occasionsRemember special occasions

Assist with transportationAssist with transportation

Financial compensationFinancial compensation

RECENT ADVANCES

Professional Recruitment providers:

Professional recruitment providers

today often work with

sponsor ,CROs and SMOs to improve

recruitment efforts at a site.

Increased use of market research

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 behavior .

Informatics

Approach to find good potential subjects.

Provide de-identified data obtained from

pharmacies , physicians , hospitals , insurance

companies, etc.

Once the population is defined an informatics

service provider would target it with a direct

mail campaign.

Centralized recruiting

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 recruitment activities.

Development of metrics - the leaky pipes analysis

Identifies the effectiveness recruitment program

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.

Conclusion

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 investigator site.

Questions ??

Thank You!!!