USING INTERACTIVE VOICE

RESPONSE (IVR) SYSTEMS TO

ASSIST WITH PATIENT
RECRUITMENT

SHUBHANKAR DEY
SACHDEVA INSTITUTE OF TECHNOLOGY, MATHURA
 What is an IVR System?

• Company and protocol-

specific pre-recorded voice
prompts
ClinPhone

• User response via the touch-

tone key pad of the telephone

• Callers input response, data

and receive instructions
based on protocol-specific
algorithms
What is an IVR System?

An IVR System
is NOT ONLY a
randomization system!
 ClinPhone•ivr applications
• Site Management
– Site activation
– Site suspension
– Payment to investigators
– Track enrolment (country level/site level)
– Control site activities through gatekeeper calls

• Patient Management
– Pre-screening and pre-qualification
– Screening
– Eligibility check
– Randomization (with patient visit schedule)
– Dose calculation
– Patient re-supply
– Patient tracking
– Recording of efficacy/safety data
– Code break
 ClinPhone•ivr applications
• Clinical Trial Supplies Management (inventory
and distribution control)
– Trigger level
– Predictive

• Patient Direct
– Diary cards
– Psychiatric rating scales (HAM-D, HAM-A, Mental Health Screener,
the Leibowitz Social Anxiety Scale, Y-BOCS and WSAS)
– Cognitive functions assessment (reaction, choice reaction, articulatory
working memory task, word recall and recognition)
– Quality of Life questionnaires
– Health Economics questionnaires

• Reporting
– Batch reports
– Web reports
– Data upload
SCOPE: assist with patient recruitment

• Pre-qualification & referral to investigators

• Screening via IVR patient diary cards

• Assessment of eligibility for subjective clinical

end-points

• Metrics for screening failures

• Tracking patients’ compliance during the

study
Benefits of using IVR for pre-screening

• Investigator cost/time saving

• Accelerated recruitment
• Unbiased sample
- Web recruitment biased by age/gender
• Increased patient honesty in sensitive areas
• Globally applicable……languages & 24/7 up-time
• Access of real time demographic, diagnostic and study
management information
• Prevention of baseline score inflation (eg HAM-D)
 IVR pre-screening

A patient contact method

• Following direct advertising via radio, TV,

newspaper, magazines, flyers etc.
- USA: common practice
- Europe: becoming accepted
• Following a clinic visit or referral by 1ry physician
• Can be used in combination with a call centre
– Cost-effective alternative to call centre alone
– Initial human interaction to take contact details may be
beneficial
• Can be used on its own
– Standardised medical interviews possible (eg HAM-D) or
pre-qualification followed by recording of patient contact
details
 IVR pre-screening

A pre-qualification method
• Diagnosis check
– Psychiatric rating scales like the Mental Health
Screener to screen mood, anxiety, eating disorders
and other substance abuse, to identify potential
patients with evidence of depression)
– Cognitive function assessments
• Disease severity
• Eligibility criteria
• Demographics
 Pre-Qualification
Referral Referral
Via TV Advertising From Site/community

Record Contact
Info Call Centre

IVR HAM-D IVR call

Eligibility
Fax to closest
study centre
Accelerated Recruitment in Depression
study
Centralised screening used in addition to study site activities

TOTAL # contacts 32,763

# Call centre screens 22,994 70%

# Pre-qualified 7,651 33%

subjects
#Pre-qualified 5,755 75%
subjects to HAMD
# Successful with 3,774 66%
HAMD (>19)
# passed on to sites 1,329 35%

Subjects randomised 677 51%(9%)

Accelerated Recruitment in Depression
study

Outcome:
– 394 and 283 subjects randomised on to the protocols
– Protocol 1 fully enrolled in 12 weeks (saved 16 weeks)
– Protocol 2 fully enrolled in 14 weeks (saved 7 weeks)
 Baseline score inflation
Case Study:
Supplementary Efficacy Data Collection

Entry Criterion
– Total baseline HAM-D > 19

Study population
– Major depressive disorder
– N = 291

Assessments
– Clinician rated HAM-D: weeks 0, 1, 2, 3, 4, 5, 6, 7, 8
– IVR HAM-D recorded (from office): weeks 0, 1, 2, 3, 4, 5, 6, 7, 8
 IVR Clinician

25

40

60
20

Visit 1 HAMD17p
30
15

40
Visit 1

20
10

20
Qualification

10
5
0

0
0 10 20 30 40 0 10 20 30 40 0 10 20 30 40
Visit 1 HAMD17p Visit 1 HAMD17c Visit 1 HAMD17c

50
20

40

40
Visit 2 HAMD17p
15

30

30
Visit 2
10

20

20
Qualification

10
5

10
0

0
0 10 20 30 40 0 10 20 30 40 0 10 20 30 40
Visit 2 HAMD17p Visit 2 HAMD17c Visit 2 HAMD17c

25
20

40

20
Visit 3 HAMD17p
15

30

Visit 3

15
10

20

10
Randomisation
10
5

5
0

0
0 10 20 30 40 0 10 20 30 40 0 10 20 30 40
Visit 3 HAMD17p Visit 3 HAMD17c Visit 3 HAMD17c
10 12

DeBrota et al.,
10 12
40
Visit 9 HAMD17p

NCDEU, 1999
30
8

Visit 9
6

20

6
4

Endpoint
10
2

2
0

0 10 20 30 40 0 10 20 30 40 0 10 20 30 40
Visit 9 HAMD17p Visit 9 HAMD17c Visit 9 HAMD17c
 Effect of baseline score inflation

Greater placebo effect

Reduced ability to show treatment related differences

Higher withdrawal rate

 IVR screening

A screening method
• Eligibility criteria
• Demographics
• Additional diagnosis checks
• Run-in treatment allocation
Benefits of using IVR for screening

• Investigator cost/time saving

• Accelerated recruitment
• Unbiased sample
- Web recruitment biased by age/gender
• Lower screening failures
• Tracking of screening failures
• Prediction on when to close pre-screening and screening
period
• Trigger of medication management – more focused supplies
• Increased patient honesty in sensitive areas
• Globally applicable……languages & 24/7 up-time
• Access of real time demographic, diagnostic and study
management information
• Prevention of baseline score inflation (eg HAM-D)
 IVR diary cards

Is essential for subjective efficacy data

– Irritable Bowel Syndrome
– Sleep depravation
– Pain
– Sexual dysfunction
– Migraine

Also valuable for other indications

– Asthma
– Diabetes
– Urinary incontinence
– Gastro
 Patient Diary Data
Self observations Observable signs or symptoms
• Incontinence episodes
• Sleep disturbance
• Home peak-flow meter reading
• Escape medication usage
• Health service usage

Subjective symptoms Primary or secondary endpoint

• Pain severity
• Fatigue severity
• Patient satisfaction

Quality of life Questionnaire instruments

• Generic instruments (eg SF-12, SF-36)
• Disease-specific instruments
Benefits of using IVR for diary cards

• Investigator cost/time saving

• Accelerated recruitment
• Unbiased sample
- Web recruitment biased by age/gender
• Lower screening failures
• Tracking of screening failures
• Prediction on when to close pre-screening and screening
period
• Trigger of medication management – more focused supplies
• Increased patient honesty in sensitive areas
• Globally applicable……languages & 24/7 up-time
• Access of real time demographic, diagnostic and study
management information
• Prevention of baseline score inflation (eg HAM-D)
Benefits of using IVR for diary cards

• Can build in logic checks and improve the quality of data

• Real-time compliance assessment / real-time alerts in case of
non-compliance / proactive patient follow up, resulting in
improved compliance and lower withdrawal rates
• Tracking of withdrawal & drop-out rates
• Date and time stamp of event
• Integration with other electronic systems (EDC, Medication
Management, Central laboratory)
– Real-time assessment of patient safety
– Study data viewable via a single channel / integrated reports
Improved Data Quality Using eDiaries
Case study

Asthma peak flow meter study

Verschelden et al., 1996. Eur Resp Journal

 Subjects (n=20) not informed that data automatically stored

 PEF monitoring for 44–131 days (mean = 89 days)
 3,482 values expected
 1,897 values recorded on paper diary
46% missing
 1,533 values recorded electronically
22% invented
 90% of written values agreed with those stored
Improved Data Quality Using eDiaries

Summary of paper diary data quality

issues

• Patients do not complete diaries when

scheduled
Car-park effect

• Data recorded erroneously

• Data invented
 Patient Adherence/Compliance

Case study:
Irritable bowel syndrome studies

Treatment period: 2 weeks screening + 12 weeks treatment

Number of active patients: 640 IBS patients

System availability: 8040 h out of 8135 h (99% up-time)

Compliance: Study 1: 83%

Study 2: 81%

Reference: Harding JP, et al. (1997) Alim Pharmacol Ther; 11:1073-6

 Patient Acceptability
How easy was it to use the IVR System? (n=449)

100
90 77
80
70
60
% 50
40
30
15
20
7
10 1 0
0
Very Easy

Neither easy
Easy

Difficult

Very difficult
nor difficult
 Patient Acceptability
How easy was it to use the IVR system? (n = 874)

Very Easy 73

Easy 17

Neither Easy Nor Difficult 8

Difficult 2

Very Difficult 0

0 20 40 60 80 100
%
(Subjects had HamD and LSAS assessments)

Katzelnick et al., ACNP 1998

 ClinPhone IVRS Diaries: Examples
Indication Measurements Patients Countries
Bronchitis Symptom diary 800 N. America, S, America.
Pneumonia Symptom diary 300 N. America, S, America.
Irritable Bowel Syndrome Symptom diary, Pain scores 800 Europe (7), Australia, New Zealand.

Irritable Bowel Syndrome Symptom diary, Pain scores 1000 Far East

Irritable Bowel Syndrome Symptom diary, Pain scores 450 S. America

GERD Symptom diary 700 N. America, Europe (8), Australia

Gastro paresis Symptom diary 500 N. America, Europe (12), Australia

Depression Cognitive function 800 USA

Depression Mental Health screener, HAM-D, 1400 USA
Symptom diary, SF-12, Health
economics
Depression HAM-D 650 N. America

Depression HAM-D 650 N. America

Pain Escape medication, Withdrawal 500 USA, UK

symptoms

Migraine Symptoms 300 N. America

Migraine Symptoms 300 N. America

Migraine Symptoms 470 Europe (9)
Contact: Maddy Lecomte
mlecomte@clinphone.com