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outcome research/screening 1
Outcome Outcome evaluation of evaluation of
screeningscreeningWei-Chu ChieWei-Chu Chie
outcome research/screening 2
Screening Screening • Secondary prevention
– early detection and prompt treatment– screening people with early, often
preclinical, manifestations of diseases, to prevent its progression
– must followed by diagnosis and treatment procedures
outcome research/screening 3
VariantsVariants• Mass screening• opportunistic screening• clinical case finding
outcome research/screening 4
Endpoints and efficacy Endpoints and efficacy evaluationevaluation
• Compare the outcomes of screened and non-screened (symptomatic) groups
• mortality– case-fatality/survival– total (overall) mortality– specific mortality
• specific morbidity
outcome research/screening 5
Case-fatality/survivalCase-fatality/survival• Count from the time of diagnosis• take only causes of death that
related to the target disease(s) of screening – lead-time bias– length bias (prognosis selection bias)
outcome research/screening 6
Overall mortalityOverall mortality• Count from the time of participation• take all causes of death
– unaffected by the ways of diagnosis or detection
– overall impact of the program • positive & negative
– sometimes insensitive
outcome research/screening 7
Specific mortalitySpecific mortality• Count from the time of participation• take only causes of death that
related to the target disease(s) of screening– may be affected by the ways of
diagnosis or detection– more sensitive– sometimes difficult to identify
outcome research/screening 8
Specific morbiditySpecific morbidity• Count from the time of participation• take only some severity indices of
the target disease(s) of screening• stages, tumor size, certain
complications, ...– not the final outcome– only surrogate in nature
outcome research/screening 9
Study designStudy design• Randomized controlled trial• non-randomized
– cohort– case-control– other variants
• meta-analysis
outcome research/screening 10
實驗性方法的三要素實驗性方法的三要素• 實驗單位 (experimental unit)• 處置 (treatment)• 評估 (evaluation)
outcome research/screening 11
實驗單位實驗單位• 個人為單位
– 病人 •藥物臨床試驗 •教育介入 如病人衛生教育
– 健康人 •疫苗預防性試驗 篩檢工具試驗•教育介入 如健康行為的養成
• 群體為單位– 社區 班級 團體
outcome research/screening 12
處置處置•新藥•新的飲食•診斷或篩檢•手術•醫療器材•教育介入•無治療
outcome research/screening 13
評估評估• 有效性
•事件 / 事件史資料 (event/time to event)• well-being 指標 : 生活品質 (quality of life)•成本 : 直接與間接醫療成本•暫時性或替代性指標 : 生理 生化 病理資料•又稱終點 (end-points)
• 安全性– 不良反應及相關指標
• 經濟學 : 成本效益
outcome research/screening 14
Common problemsCommon problems• No blindness
– screener– subjects– evaluator or rater
• sometimes randomized by cluster for the convenience of intervention– statistical help
outcome research/screening 15
ExamplesExamples• Breast self-examination for breast
cancer– mass screening
• General health screening for cardiovascular risks– by general practitioners
• Case-finding for depression in primary care– by general practitioners
outcome research/screening 16
BSEBSE• Thomas DB., et al. Randomized trial
of breast self-examination in Shanghai: final results. JNCI 2002; 94:1445-1457.
outcome research/screening 17
BSE: BSE: background/goal/hypothesisbackground/goal/hypothesis
• Background: – BSE efficacy unproven
• Goal:– to determine whether ...
• Hypothesis: – an intensive program of BSE instruction
will reduce the mortality (number of death ) of breast cancer
outcome research/screening 18
BSE: study designBSE: study design• Randomized controlled trial
– instruction group– control group– randomized by cluster (factories)
stratified by hospital affiliation– no statistical adjustment: large number
and identical rates
• mass screening
outcome research/screening 19
BSE: subjects BSE: subjects • Shanghai Textile Industry Bureau
(STIB) employees• women born between 1925-1958
(31-64)• eligibility, inclusion/exclusion criteria• 289292 ….266064
– instruction: 146437 …. 132979– control: 142955 …. 133085
outcome research/screening 20
BSE: exposure/interventionBSE: exposure/intervention• BSE instruction
– small group (10)– video/practice/discussion/reinforcement– review/supervision– proficiency assessment
outcome research/screening 21
BSE: endpointBSE: endpoint• Primary: death from breast cancer
– definition– judgement: blind
• Secondary?– Intermediate variables: benign
tumors/biopsies
• Follow-up: 11 years
outcome research/screening 22
BSE:data analysis BSE:data analysis • Survival
– from time of entry– from time of diagnosis
• Kaplan-Meier/log-rank test• Cox proportional hazards model
• comparability , compliance, …• intermediate variables
outcome research/screening 23
BSE: major BSE: major results/discussionresults/discussion
• Mortality/survival– from entry– from diagnosis
• comparability, compliance, …• intermediate variables
– benign tumors … biopsy (unnecessary burden)
outcome research/screening 24
CRSCRS• Engberg M., et al. General health screeni
ngs to improve cardiovascular risk profiles: a randomized controlled trial in general practice with 5-year follow-up. J Family Practice 2002;51:546-552.
outcome research/screening 25
CRS: CRS: background/goal/hypothesisbackground/goal/hypothesis
• Background: Danish trial– GP’s role in primary prevention for CVD
• Goal:– to investigate the impact of general
health screenings and health discussions on CV risk profiles
• Hypothesis: – … can reduce ...
outcome research/screening 26
CRS: study designCRS: study design• Randomized controlled trial
– 3 groups– by individual– stratified randomization based on
• GP, sex, age, cohabitation status, BMI
– too many cells• GP X sex X age X …
– stratified factors should be treated as covariates
outcome research/screening 27
Stratified randomizationStratified randomization– Individuals stratified by certain characteristi
cs– Independent random assignment to differe
nt groups in each cell• eg. Old-male, old-female, young-male, …• random code for each consecutive subject• can be generated by computer
– To avoid imbalance• may have empty cells if N is small• no need when N is large
outcome research/screening 28
CRS: subjects CRS: subjects • Ebeltoft, Aarhus County, Denmark• 9 GPs (general practitioners)• 3464 … random sample 2000 inhabitant
s• 30-49 years
outcome research/screening 29
CRS: exposure/interventionCRS: exposure/intervention• Health screening & follow-up
discussion– Group 1: health screening (502)– Group 2: health screening+follow-up
discussion (504)– Group 3: none (control) (501)– All three: questionnaire
outcome research/screening 30
CRS: endpointCRS: endpoint• Primary: score and categorical (high/low)
– CRS: gender, family inheritance (CAD <55 y), tobacco use, BP, total serum cholesterol, BMI
– BMI, SBP, DBP, serum cholesterol• by smoking and overweight subgroup
analysis
– No blindness• Follow-up: 5 years
outcome research/screening 31
CRS:data analysis CRS:data analysis • T-test, chi-square, …• intention-to-treat• compare values or high score rates
instead of changes from baseline– endpoints– baseline data– follow-up rates
outcome research/screening 32
CRS:major CRS:major results/discussionresults/discussion
• CRS, BMI, and serum cholesterol levels were lower in the Intervention group
• subgroup analysis: high vs. low risk ones
• no differences between two intervention groups
• not followed to the final endpoint
outcome research/screening 33
DepressionDepression• Williams JW. , et al. Case-finding for
depression in primary care: a randomized trial. Am J Med 1999; 106: 36-43.
outcome research/screening 34
Dep: background/goal/hypothesisDep: background/goal/hypothesis• Background:
– impact of depression/role of primary care
• Goal:– evaluate the efficacy of two case-finding
instruments vs. usual care
• Hypothesis: – … can enhance symptom reduction/recovery
for depression patients
outcome research/screening 35
Dep: study designDep: study design• Randomized controlled trial
– 3 groups– by individual– random assignment stratified by site
• computer-generated randomization blocked log
outcome research/screening 36
Dep: subjects Dep: subjects – GP and internal medicine clinics in San
Antonio, Texas and Washington, DC.– Consecutive adult patients– Only those diagnosed as with depression
were analyzed• screened with case-finding: positive---
additional questioning for clinical depression• all patients: DSM-III-R, CAGE, SF-36,
satisfaction• rater (evaluator) blindness
outcome research/screening 37
Dep: exposure/interventionDep: exposure/intervention• Case-finding instruments screening
– Group 1: single question (330)– Group 2: 20 item questionnaire (323)– Group 3: usual care (control) (316)
outcome research/screening 38
Dep: endpointDep: endpoint• Primary: only depressive patients
– recovery rates (<=1 DSM-III-R symptoms)
– symptoms score changes from baseline
• Secondary:– satisfaction
• Follow-up: 3 months
outcome research/screening 39
Dep:data analysis Dep:data analysis • Proportion and rates• Symptom numbers
– only for patients diagnosed as with depressions
– not severity indices– by medical record: counseling, referral,
medicine
• baseline data• follow-up rates
outcome research/screening 40
Dep:major results/discussionDep:major results/discussion• Recovery rate:
– case-finding better than usual care
• symptoms numbers– not different
• Only diagnosed patients were analyzed
• not followed to the final endpoint