Transcript China Adherence for Life study: Key findings from Phase III 终身依从性第三阶段主要研究结果. 中国 April 14, 2008 Dr.

China Adherence for Life study:
Key findings from Phase III
终身依从性第三阶段主要研究结果. 中国
April 14, 2008
Dr. Lora Sabin
Dr. Mary Bachman DeSilva
Dr. Donald Thea
Center for International Health and
Development
Department of International Health
Boston University School of Public Health
波士顿大学公共卫生学院 国际卫生和发
展中心
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AFL: study collaborators 依从性终身性研究合作伙伴
Boston University SPH 波士顿大学公共卫生学院
Lora Sabin, MA, PhD
Christopher J. Gill, MS, MD
Mary Bachman DeSilva, MS, ScD
Davidson H. Hamer, MD
Dali Second People’s Hospital 大理第二人民医院
Zhang Jianbo, MD
Ditan Hospital 北京地坛医院
Xu Keyi, MD
Horizon Research Group 横向研究小组
Yuan Yue, MA, PhD
Fan Wen, MA
US CDC-GAP Office 美国疾病控制中心全球艾滋病项目
World Health Organization – Beijing 世界卫生组织驻华代表处
Funding provided by: USAID, WHO/Beijing, US CDC
资金提供方：美国国际发展署，世界卫生组织，美国疾病预防控制中心
Additional acknowledgments特别感谢: Don Thea, Jon Simon, Deirdre Pierotti, Anna
Knapp, Li Tao, Wan-ju Wu, Guo Jianhua, Matt Bobo, Ahmar Hashmi, and Jordan Tuchman
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Overview of AFL
(Control对照)
Continued passive
observation连续被动
观察
(Intervention干预)
N=80
Patients enrolled录入病人
Active EDM
feedback EDM主动
反馈
N=68
随机.病人Patients randomized
Phase I 第一阶段
Phase II第二阶段
Phase III第三阶段
6 months 6个月
6 months 6个月
6 months 6个月
Qualitative investigations
on what patients/doctors in
Dali view as key barriers to
adherence
Adherence observed
prospectively via EDM,
relationship between barriers
and actual adherence, clinical
outcomes measured
Randomized controlled trial
to determine effectiveness of
EDM data feedback strategy
通过定性研究在大理的病人/医
生中了解影响依从性的主要障碍
通过EDM观察依从性的预期效果：
影响依从性的障碍因素和临床结果
的测量间的关系
随机对照研究：确定EDM
资料反馈策略方法的有效性
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Efficacy of behavioral interventions in achieving
≥95% adherence rates
行为干预对获得≥95％依从性的效用
Simoni, JAIDS 2006
Control betterd
对照更好
Intervention better
干预更好
4
Poorer efficacy of behavioral interventions for achieving
UDVL行为干预对于取得“病毒载量无法检测”效用更
差
1.
9/13 studies show no significant
benefit
9/13研究显示无明显好处
1.
6/13 with point estimate
suggesting intervention was
paradoxically harmful
6/13显示使用建议的干预方法是有
反向的害处
OR=1.25, but 95%CI
straddles 1.0
Simoni, JAIDS 2006
Control better Intervention better
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What is the EDM feedback intervention?
究竟什么是EDM反馈性干预？
•
•
Systematically use EDM data in clinical encounters
临床中系统性使用EDM数据
Designed to address limitations of current standard of care: 强调
目前关怀标准的局限性
•
Clinician’s assessment influenced by subjective information due to
patient self report
临床医生的评估受到病人自我报告的主观信息的影响
• Delay before poor adherence translates into adverse clinical outcomes
未在临床症状出现前提示依从性差
•
Advantages of EDM feedback: EDM反馈的优势
•
Adherence assessment based on objective data
依从性评估基于客观数据和资料
• Ability to assess changes in adherence quickly, without needing to wait
for clinical markers
快速评估依从性改变，而无需等待临床症状
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What happened in intervention group?
干预组的情况如何呢？
• Intervention group 干预组
• EDM data reviewed at each monthly study visit by study team member
项目组成员每个月均到现场查看EDM数据结果
• EDM data given to doctor and patient at each visit
每次现场督导时均将EDM数据与医生和病人分享
• Patients with <95% adherence by EDM in previous month flagged for
“additional adherence counseling” with doctor
最初几个月EDM数据显示：病人依从性<95%，则将其标记为需要
医生再提供“依从性咨询”
• Additional counseling had no script; it involved a conversation between
doctor and patient in which doctor asked about problems or challenges
faced, referring to EDM print-out
“依从性咨询”无手稿记录，是医生和病人间的对话，包含依从性
方面的问题和挑战，内容在EDM打印件中
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What happened in control group?
对照组的情况如何？
• Control group对照组
• Self-report data reviewed at each monthly study visit by study team
member
项目组成员每个月均到现场查看自我报告数据
• EDM data not provided to doctor/patient
EDM数据不提供给医生或者病人
• Patients with <95% adherence by self report in previous month
flagged for “additional adherence counseling” with doctor
最初几个月自我报告数据显示：病人依从性<95%，则将其标记为
需要医生再提供“依从性咨询”
• Like intervention arm, additional counseling involved a conversation
in which doctor asked about problems or challenges faced, referring to
patient’s self-report
与干预组一样，“依从性咨询”是医生和病人间的对话，包含依
从性方面的问题和挑战，内容见病人自我报告
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Randomization Procedure 随机操作程序
• In Phase II, all patients followed for 6 months using EDM; EDM data not
given to patients or clinicians
第二阶段，所有病人使用EDM随访6个月；EDM数据不给与病人和医
生
• At end of Phase II, patients stratified by ‘high’ or ‘low’ adherence (≥95%
or <95% mean adherence from Months 0-5, using EDM composite
measure)
第二阶段结束，将病人按照依从性情况分成“高依从性”和“低依从
性”（按照EMD合成方法，0-5个月的平均依从性结果：≥95％ 或者
<95%）
• Patients in each stratum randomized to intervention or control group
(“block randomization” approach)
干预组和对照组中，每一层的病人随机分组（“随机整群”方法）
 Result: no bias introduced by disproportionate allocation of high/low
adherers to one group
结果：依从性高/低组无统计学偏差性
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Phase III: objectives第三阶段：目标
1. To determine whether EDM feedback is effective in
improving adherence among intervention group relative to
control group
确定EDM反馈法：相比对照组，促进了干预组的依从性
2. To determine whether the intervention group experiences an
improvement in clinical indicators relative to control group
确定干预组在临床指标上与对照组是否有改善
Note – the study was powered to detect a 15% difference in adherence
rates, as assessed by EDM, but not for a difference in clinical
outcomes.
注-研究结果显示干预组比对照组的依从性提高了15％，有明显差
异，尽管在临床指标上无明显差异（EDM评估结果）
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Methods: EDM measures used in the analysis
方法：EDM测量用于评估
1. Proportion of doses taken 服药量比例

# doses taken
服药量
# prescribed doses医生处方药量
2. Composite EDM measure, incorporating proportion
taken and proportion taken on time
合成EDM方法，即服药量比与按时服药比例

# doses taken +/- 1 hour of scheduled time服药量和时间＋/-1小时（既定服药时间）
# prescribed doses医生处方药量
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Methods: clinical measures方法：临床测量
(assessed at Month 6 and Month 12，6个月和12个月进行评估)
•
•
CD4 count (continuous) CD4计数
Viral load (binary; <400 copies= “undetectable”)
病毒载量（二元的；<400复制数＝“未检测出病
毒”）
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Results: Patient Characteristics at time of randomization (Month 6)
结果：病人随机分组特点（6个月）
Intervention
Characteristic
Gender
Male
Female
Number (%) Mean (SD)
25 (74)
9 (26)
Age (Mean, SD)
Control
Number (%) Mean (SD)
25 (74)
9 (26)
36.1 (8.3)
35.1 (8.0)
Education*
Elementary
Junior high
Senior high/technical school
7 (21)
17 (50)
10 (29)
13 (38)
20 (59)
1 (3)
Marital status
Single
Married
15 (44)
19 (56)
16 (47)
18 (53)
Ethnic background
Han Chinese
Bai
Other
18 (53)
14 (41)
2 (6)
15 (44)
17 (50)
2 (6)
Household size
Employment status
Currently employed
Currently unemployed
4.2 (1.5)
10 (31)
22 (69)
4.5 (1.4)
12 (37)
20 (63)
* Statistically significant at the p<.01 level 统计学分析有显著差异，p<.01
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Results: Patient Characteristics
at time of randomization (Month 6)
结果：病人随机分组特征
Characteristic
Heroin use in previous 3 mos
Yes
No
Intervention
Control
Number (%) Mean (SD)
Number (%) Mean (SD)
4 (12)
30 (88)
Depression (Beck's, continuous)
Depression (Beck's, binary)
Yes
No
9.8 (3.6)
6 (18)
27 (82)
CD4, Month 6 (continuous)
UDVL, Month 6 (yes)
5 (15)
29 (85)
10.2 (4.0)
10 (30)
23 (70)
297 (145)
357 (196)
30 (88.2)
28 (87.5)
16 (47)
18 (53)
17 (50)
17 (50)
Mean adherence, Months 0-5**
High (>= 95%)
Low (<95%)
** basis for block randomization procedure整群随机分组过程的基础
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Mean adherence in Month 6 and Month 12
项目研究6个月和12个月平均依从性
Comparison of mean adherence levels Intervention v. Control Groups
using EDM measures
干预组和对照组平均依从性比较
Month 6
Month 12
Intervention
Mean (SD)
Control
Mean (SD)
Intervention
Mean (SD)
Control
Mean (SD)
n=31
n=33
n=30
n=33
Proportion doses taken
0.955 (.094)
0.955 (.092)
.983 (.014)
.957 (.071)*
Composite measure
0.868 (.185)
0.839 (.218)
0.964 (.048)
.845 (.210)**
Measure
P-values for Month 12 comparisons: * significant at p<0.05, ** significant at p<0.01.
At Month 6, no differences between intervention/control groups were statistically significant
at the p<=.05 level.
12个月时P值：*显著差异p<0.05，显著差异p<0.01；6个月时：对照组/干预组无显
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著统计学差异，p<=.05
Mean adherence in Phase II and phase III
第二阶段和第三阶段的平均依从性
Comparison of mean adherence levels Intervention v.
Control Groups using EDM measures
对照组和干预组平均依从性的比较
Months 1-6
Months 7-12
Intervention
Mean (SD)
Control
Mean (SD)
Intervention
Mean (SD)
Control
Mean (SD)
n=31
n=33
n=30
n=33
Proportion doses taken
0.969 (.035)
0.976 (.024)
.989 (.009)
.965 (.039)**
Composite measure
0.895 (.138)
0.873 (.167)
0.965 (.034)
.841 (.214)**
Measure
P-values for Months 7-12 comparisons: ** significant at p<0.01.
For Months 1-6, no differences between intervention/control groups were statistically
significant at the p<=.05 level.
7－12个月的对比：显著差异p<.01;1-6个月，对照组和干预组无显著差异p<=.05
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Monthly adherence for each group: Composite: Adherence Measure
每组月度依从性：综合：依从性测量方法
Monthly adherence*, Intervention vs. control,
China AFL study
(*composite adherence measure using EDM data)
1
0.95
0.9
0.85
Percent
0.8
Intervention
Control
0.75
0.7
0.65
0.6
0.55
0.5
1
2
3
4
5
6
7
8
9
10
11
12
Study month
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Monthly adherence for each group: Composite Adherence Measure
每个组月度依从性：综合依从性测量方法
Effect of EDM feedback on rates of optimal adherence
at month 12
Proportion with Adherence >95%
100
RR 2.2
(1.4-3.5)***
RR 6.4
(1.7-24.2)***
90
80
RR 1.4
(0.9-2.0)
91.7
82.1
75.0
70
66.7
60
50
40
30
37.5
20
10
11.8
0
All patients
Low adherers
Intervention
Control
High adherers
Group
P-values for risk ratios: *** significant at p<0.001. P值危险比：显著差异p<.001
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Monthly adherence for each group, by high v low adherence at
randomization: Composite: Adherence Measure
每组月度依从性：综合：依从性测量方法
100%
95%
90%
Adherence
85%
80%
75%
70%
65%
60%
Low adherers, intervention group
Low adherers, control group
55%
High adherers, intervention group
High adherers, control group
50%
1
2
3
4
5
6
7
Month
8
9
10
11
12
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Achievement of mean adherence ≥95% during Phase III
(Months 7-12) 第三阶段成绩：平均依从性≥95%
Patients maintaining 95% adherence or above
in Months 7-12
Using EDM composite measure
Intervention
All patients
Control
N
Number (%)
N
Number (%)
Risk ratio [95% CI]
31
23 (74.2)
33
11 (33.3)
2.23 [1.32-3.76]**
P-values for risk ratio: ** significant at p<0.01.
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Clinical outcomes：Intervention vs. Control groups,
Month 12 临床结果：干预组和对照组在12个月的比较
Intervention
Control
Variable
Mean (SD) Number (%)
n=31
n=31
Min Max
Mean (SD) Number (%)
n=33
n=33
Min Max
CD4, Month 12 (continuous)
401 (256)
356 (157)
UDVL, Month 12 (yes)
64 1085
27 (87)
120 644
31 (94)
•Differences in CD4 counts and UDVL proportions between intervention/control
groups were not statistically significant at the p<=.05 level
不同CD4计数和“UDVL”：干预组和对照组无明显统计学差异P<=.05
21
Improvement in CD4 count between Months 6 and 12
CD4计数的提高:6-12月间
Intervention
Variable
Mean (SD)
n=31
Increase in CD4 (yes)
Change in CD4 (continuous)
Number (%)
n=31
Control
Mean (SD) Number (%)
n= 31
n=31
22 (71.0)
90 (172)
* Significant at the p<=.05 level 显著差异：P<=.05
15 (48.4)
-9 (153)*
22
Patient-level EDM view: A near perfect patient profile
病人角度的EDM：几乎完美的病人档案图示
23
Patient-level EDM view: A patient with poor adherence
病人角度EDM：一个依从性差病人的图示
24
Patient-level EDM view: A patient with improved adherence
病人角度EDM：一个依从性改善病人的图示
25
Patient-level EDM view:
A patient with improved adherence
26
Conclusions 结论
• EDM feedback led to sustained increase in adherence in intervention group vs.
controls over 6 month period
经过6个月， 与对照组比较，EDM反馈可以持续性提高干预组依从性
• Mean adherence was significantly higher at Month 12
12个月时，平均依从性显著增高
• Mean adherence was significantly higher over Months 7-12
平均依从性自7－12月显著提高
• Likelihood of achieving ≥95% adherence at Month 12 was significantly higher
经过12个月，依从性可以获得≥95% 的水平
• EDM feedback led to a large mean increase in CD4 count compared to a mean
decline among controls
EDM反馈方法可以相对促进CD4计数，特别是与对照组所出现的一个CD4
计数平均水平下降的情况相比较
• The small number of patients with detectable VL precluded meaningful analysis
of UDVL data
少数病人的病毒载量可以检测，这更加显示UDVL数据的意义
27
Future directions/research needs
未来的方向/研究需求
• How generalizeable are the results of this study?
这个研究结果的推广普及性？
• How applicable to other patient groups in China?
这个研究对于其他病人的可应用性
• How applicable to other clinical settings?
这个研究对于其他临床场所的可应用性？
• How applicable outside of China?
这个研究对于中国以外国家的可应用性？
• A larger trial is needed - powered to detect changes in CD4 and UDVL rates
需要扩大研究-特别是CD4计数和UNVL检测率
• Is a multi-site study desirable? 需要一个多点研究吗？
• EDM feedback method highly promising BUT:
EDM反馈方法非常好但是：
• Can patients come off of EDM feedback, or must this be continued indefinitely?
病人无需继续进行EDM反馈，或者必须永远进行EDM反馈？
• Cost implications of intervention?
干预所含的花费意味着什么？
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