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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
AZithroMycin and Asthma:
Trial In Community Settings

Chlamydia pneumoniae and asthma
– Koch’s postulates
– Hill’s criteria


Effectiveness RCT
Pilot results
http://www.dean.org/index.php/info/asthma
ASTHMA Pilot Study: results
Overall Asthma Symptoms
Symptom Score
3
2
Azithro
Placebo
1
0
1
2
3
4
5
6
Study Month
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.
Effectiveness versus Efficacy

Efficacy
– Highly selected population
– Lots of exclusions
– Get rid of “noise”

Effectiveness
– Representative population
– Minimize exclusions
– “Noise” = “Our Patients”
Effectiveness Studies: the Ideal
Included
Excluded
Asthma Studies: the Reality
Included
Excluded
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
Current Clinical Trials
Setting
No. subjects
Treatment
Duration
1o Outcome
Design
Cost
AZMATICS
PBRNs
600
Azithro,x12w
1 year
Symptoms
Effectiveness
3.5M
MIA
ACRN
144
Clarithro,x16w
6 months
Control
Efficacy
12.5M
Underfunded AZMATICS
Email/Internet Data Collection
 Volunteer Study Clinicians
 Volunteer Study Subjects
 Symptoms, Med Use, QOL, Exacerbations

– No Pulmonary Function
– No Biomarkers
Recruitment
22 Individuals randomized 74 subjects
35
30
25
20
15
10
5
0
ANSR
MARSH
NRN
OKPRN
RAP
WREN
Recruitment
20 Eligible Subjects Declined Randomization
N=20
N=74
Randomized
Open Label
Subject Demographics
Randomized (74)
Open Label (20)
Age, median (range)
46 (21-80)
44 (21-80)
Gender
51F, 23M
8F, 12M
Smoking, % current
16
0
Asthma onset, Age
23 (0-57)
21 (6-53)
“Infectious”, %
33
55
“Pure” Asthma, %
77
85
AS-CAO, %
12
5
Prior attacks, %
64
60
Baseline severity
1.4Day, 1.6Noc
2.0Day, 1.8Noc
P<.05
P<.01
Subject Retention
Randomized Cohort
31%
60%
9%
Completed
Still In
LTFU
Main Findings

Despite inadequate funding
– AZMATICS is being successfully implemented
– AZMATICS will provide Level 2 Evidence


Completion rate <80%
An external validity control group is potentially
important
– Open Label subjects are different
Summary
Effectiveness studies are long overdue
 The evidence for infection in asthma is robust
 Practice-based RCTs are feasible and should be
funded

Final Comment
“No Funding is Not Enough”