USING INTERACTIVE VOICE

RESPONSE (IVR) SYSTEMS TO

ASSIST WITH PATIENT
RECRUITMENT

What is an IVR System?

Company and protocolspecific pre-recorded voice
prompts
ClinPhone

User response via the touchtone 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!

ClinPhoneivr 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

ClinPhoneivr 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 applicablelanguages & 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
Via TV Advertising

Referral
From Site/community

Record Contact
Info

IVR HAM-D

Eligibility
Fax to closest
study centre

Call Centre

IVR call

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
subjects

7,651

33%

#Pre-qualified
subjects to HAMD

5,755

75%

# Successful with
HAMD (>19)

3,774

66%

# 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

Clinician
60
40

30

20

20
0

10

20

30

40

Visit1HAMD17p

15
10
5
0

Visit 1
Qualification

10

20

40

25

IVR

30

40

10

20

30

40

40
30

30

20

20

20

30

40

10
0

Visit2HAMD17p

10
0

10

10

20

30

40

20

30

40

25
15
10

20

30

40

40

10

20

30

40

DeBrota et al.,
NCDEU, 1999

10 12

40

30

20

2
0

Visit9HAMD17p

10
0

30

Visit 3 HAMD17c

12
10
8
6
4
2

20

Visit 9 HAMD17p

40

10

Visit 3 HAMD17c

10

30

Visit 3 HAMD17p

20

20

40
30
20

Visit3HAMD17p

10

10

Visit 2 HAMD17c

10

15
10
5
0

Visit 2 HAMD17c

20

Visit 2 HAMD17p

Visit 9
Endpoint

Visit 1 HAMD17c

40

20
15
10
5

Visit 3
Randomisation

20

Visit 1 HAMD17c

Visit 2
Qualification

10

50

Visit 1 HAMD17p

10

20

30

Visit 9 HAMD17c

40

10

20

30

Visit 9 HAMD17c

40

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 recrutement
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 applicablelanguages & 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 applicablelanguages & 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 44131 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:
Study 2:

Reference:

83%
81%

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

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

77

0
Very difficult

Neither easy
nor difficult

Easy

Difficult

15

Very Easy

100
90
80
70
60
% 50
40
30
20
10
0

Patient Acceptability
How easy was it to use the IVR system? (n = 874)
73

Very Easy
Easy

17
8

Neither Easy Nor Difficult

Difficult
Very Difficult

0
0

20

40

(Subjects had HamD and LSAS assessments)

60

80

100

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,

Symptom diary, SF-12, Health
economics

1400

USA

Depression

HAM-D

650

N. America

Depression

HAM-D

650

N. America

Pain

Escape medication, Withdrawal

symptoms

500

USA, UK

Migraine

Symptoms

300

N. America

Migraine

Symptoms

300

N. America

Migraine

Symptoms

470

Europe (9)