USING INTERACTIVE VOICE RESPONSE IVR SYSTEMS TO ASSIST

USING INTERACTIVE VOICE RESPONSE (IVR) SYSTEMS TO ASSIST WITH PATIENT RECRUITMENT Maddy Lecomte Business Manager Clin. Phone Group Limited

What is an IVR System? • Company and protocolspecific pre-recorded voice prompts Clin. Phone • 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!

Clin. Phone • 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

Clin. Phone • ivr applications • Clinical Trial Supplies Management (inventory and distribution control) – Trigger level – Predictive • Patient Direct • Reporting – 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 – 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 1 ry 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 1. Case Study: 2. 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 Visit 1 Qualification Visit 2 Qualification Visit 3 Randomisation Visit 9 Endpoint De. Brota et al. , NCDEU, 1999

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 e. Diaries 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 e. Diaries 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)

Patient Acceptability How easy was it to use the IVR system? (n = 874) Very Easy Neither Easy Nor Difficult Very Difficult % (Subjects had Ham. D and LSAS assessments) Katzelnick et al. , ACNP 1998

Clin. Phone 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 Pain Escape medication, Withdrawal symptoms 500 USA, UK Migraine Symptoms 300 N. America Migraine Symptoms 470 Europe (9)

Contact: Maddy Lecomte mlecomte@clinphone. com