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

2. Company and protocol- specific pre-recorded voice prompts 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? ClinPhone

3. An IVR System is NOT ONLY a randomization system! What is an IVR System?

4. 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

5. 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

6. 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

7. 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)

8. 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

9. 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

10. 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

11. Accelerated Recruitment in Depression study Centralised screening used in addition to study site activities TOTAL # contacts32,763 # Call centre screens22,99470% # Pre-qualified subjects 7,65133% #Pre-qualified subjects to HAMD 5,75575% # Successful with HAMD (>19) 3,77466% # passed on to sites1,32935% Subjects randomised67751%(9%)

12. 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)

13. 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 Baseline score inflation

14. DeBrota et al., NCDEU, 1999 Visit 1 Qualification Visit 2 Qualification Visit 9 Endpoint Visit 3 Randomisation IVRClinician

15. Greater placebo effect Reduced ability to show treatment related differences Higher withdrawal rate Effect of baseline score inflation

16. IVR screening A screening method Eligibility criteria Demographics Additional diagnosis checks Run-in treatment allocation

17. 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)

18. 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

19. Self observationsObservable signs or symptoms Incontinence episodes Sleep disturbance Home peak-flow meter reading Escape medication usage Health service usage Subjective symptomsPrimary or secondary endpoint Pain severity Fatigue severity Patient satisfaction Quality of lifeQuestionnaire instruments Generic instruments (eg SF-12, SF-36) Disease-specific instruments Patient Diary Data

20. 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)

21. 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

22. 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

23. 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

24. 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

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

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

27. ClinPhone IVRS Diaries: Examples N. America300SymptomsMigraine Europe (9)470SymptomsMigraine N. America300SymptomsMigraine USA, UK500Escape medication, Withdrawal symptoms Pain N. America650HAM-DDepression N. America650HAM-DDepression USA1400Mental Health screener, HAM-D, Symptom diary, SF-12, Health economics Depression USA800Cognitive functionDepression N. America, Europe (12), Australia500Symptom diaryGastro paresis N. America, Europe (8), Australia700Symptom diaryGERD S. America450Symptom diary, Pain scoresIrritable Bowel Syndrome Far East1000Symptom diary, Pain scoresIrritable Bowel Syndrome Europe (7), Australia, New Zealand. 800Symptom diary, Pain scoresIrritable Bowel Syndrome N. America, S, America.300Symptom diaryPneumonia N. America, S, America.800Symptom diaryBronchitis CountriesPatientsMeasurementsIndication

28. Contact: Maddy Lecomte mlecomte@clinphone.com