1. Recruitment, Retention and Adherence in an Under-funded AZMATICS Study David L. Hahn, M.D., M.S. (Epidemiology) Dept. Family Practice, Dean Medical Center Clinical Professor, U. Wisconsin Dept. Family Medicine

2. AZithroMycin and Asthma: Trial In Community Settings l Chlamydia pneumoniae and asthma –Koch’s postulates –Hill’s criteria l Effectiveness RCT l Pilot results http://www.dean.org/index.php/info/asthma

3. ASTHMA Pilot Study: results Hahn DL, Plane MB, Mahdi OS, Byrne GI. Secondary outcomes of a pilot randomized trial of azithromycin treatment for asthma. PLoS Clin Trials. 2006;1(2):e11 DOI: 10.1371/journal.pctr0010011.

4. Effectiveness versus Efficacy l Efficacy –Highly selected population –Lots of exclusions –Get rid of “noise” l Effectiveness –Representative population –Minimize exclusions –“Noise” = “Our Patients”

5. Effectiveness Studies: the Ideal

6. Asthma Studies: the Reality Travers J, Marsh S, Williams M, et al. External validity of randomised controlled trials in asthma:to whom do the results of the trials apply? Thorax. 2007;62:219-223. Herland K, Akselsen J-P, Skjønsberg OH, Bjermer L. How representative are clinical study patients with asthma or COPD for a larger "real life" population of patients with obstructive lung disease? Respir Med. 2005;99:11-19

7. Current Clinical Trials AZMATICSMIA SettingPBRNsACRN No. subjects 600144 TreatmentAzithro,x12wClarithro,x16w Duration 1 year 6 months 1 o Outcome SymptomsControl DesignEffectivenessEfficacy Cost3.5M12.5M

8. Underfunded AZMATICS l Email/Internet Data Collection l Volunteer Study Clinicians l Volunteer Study Subjects l Symptoms, Med Use, QOL, Exacerbations –No Pulmonary Function –No Biomarkers

9. Recruitment 22 Individuals randomized 74 subjects

10. Recruitment 20 Eligible Subjects Declined Randomization N=74 N=20

11. Subject Demographics Age, median (range) 46 (21-80) 44 (21-80) Gender 51F, 23M 8F, 12M Smoking, % current 160 Asthma onset, Age 23 (0-57) 21 (6-53) “Infectious”, % 3355 “Pure” Asthma, % 7785 AS-CAO, % 125 Prior attacks, % 6460 Baseline severity 1.4Day, 1.6Noc 2.0Day, 1.8Noc Randomized (74) Open Label (20) P<.01 P<.05

12. Subject Retention 60% 9% 31% Randomized Cohort

13. Main Findings l Despite inadequate funding –AZMATICS is being successfully implemented –AZMATICS will provide Level 2 Evidence l Completion rate <80% l An external validity control group is potentially important –Open Label subjects are different

14. Summary l Effectiveness studies are long overdue l The evidence for infection in asthma is robust l Practice-based RCTs are feasible and should be funded

15. Final Comment “No Funding is Not Enough”