Outcome evaluation of screening WeiChu Chie outcome researchscreening

Outcome evaluation of screening Wei-Chu Chie outcome research/screening 1

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 2

Variants • Mass screening • opportunistic screening • clinical case finding outcome research/screening 3

Endpoints and efficacy evaluation • Compare the outcomes of screened and non-screened (symptomatic) groups • mortality – case-fatality/survival – total (overall) mortality – specific mortality • specific morbidity outcome research/screening 4

Case-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 5

Overall 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 6

Specific 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 7

Specific 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 8

Study design • Randomized controlled trial • non-randomized – cohort – case-control – other variants • meta-analysis outcome research/screening 9

實驗性方法的三要素 • 實驗單位 (experimental unit) • 處置 (treatment) • 評估 (evaluation) outcome research/screening 10

Common problems • No blindness – screener – subjects – evaluator or rater • sometimes randomized by cluster for the convenience of intervention – statistical help outcome research/screening 14

Examples • 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 15

BSE • Thomas DB. , et al. Randomized trial of breast self-examination in Shanghai: final results. JNCI 2002; 94: 1445 -1457. outcome research/screening 16

BSE: background/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 17

BSE: 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 18

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 19

BSE: exposure/intervention • BSE instruction – small group (10) – video/practice/discussion/reinforcement – review/supervision – proficiency assessment outcome research/screening 20

BSE: endpoint • Primary: death from breast cancer – definition – judgement: blind • Secondary? – Intermediate variables: benign tumors/biopsies • Follow-up: 11 years outcome research/screening 21

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 22

BSE: major results/discussion • Mortality/survival – from entry – from diagnosis • comparability, compliance, … • intermediate variables – benign tumors … biopsy (unnecessary burden) outcome research/screening 23

CRS • Engberg M. , et al. General health screenings 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 24

CRS: background/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 25

CRS: 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 26

Stratified randomization – Individuals stratified by certain characteristics – Independent random assignment to different 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 27

CRS: subjects • Ebeltoft, Aarhus County, Denmark • 9 GPs (general practitioners) • 3464 … random sample 2000 inhabitants • 30 -49 years outcome research/screening 28

CRS: 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 29

CRS: 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 30

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 31

CRS: major results/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 32

Depression • Williams JW. , et al. Case-finding for depression in primary care: a randomized trial. Am J Med 1999; 106: 36 -43. outcome research/screening 33

Dep: 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 34

Dep: study design • Randomized controlled trial – 3 groups – by individual – random assignment stratified by site • computer-generated randomization blocked log outcome research/screening 35

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 36

Dep: 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 37

Dep: 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 38

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 39

Dep: 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 outcome research/screening 40