1

整合性預防保健服務評價指標設計理念及目的

國立臺灣大學預防醫學研究所

陳秀煕 教授

2005/04/27

大　綱

•Part I整合性預防保健服務評價指標建立之必要性

•Part II整合性預防保健服務評價指標之建立

2

Part I

整合性預防保健服務評價指標建立之必要性

整合性預防保健服務評價指標建立之必要性

• 疾病流行病學之趨勢改變

• 多重預防政策(初段預防vs次段預防)之抉擇

• 疾病自然史之複雜性

• 多重篩檢工具之選擇

• 篩檢，轉介及臨床人力供需之考量

• 篩檢決策之經濟評估

• 篩檢決策之實證醫學

3

疾病流行病學之趨勢改變

Secular trend of age-adjusted mortality (per 100,000) of oral cancer by gender in Taiwan, 1993-2000

0

2

4

6

8

10

12

14

1993 1994 1995 1996 1997 1998 1999 2000

Year

Mor

talit

Male

Female

4

Secular trend of age-adjusted incidence (per 100,000) of oral cancer by gender in Taiwan, 1979-1999

0

5

10

15

20

25

30

1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 Year

Inci

denc

Male

Female

Average cigarette, alcohol and areca nut consumption per head of aged over 15 years population in Taiwan, 1966-1993

Source: Ho et al, J Oral Pathol Med 2002: 31: 213-9

Over ~2million people (10% of population) chew betel quids

5

Lao-Hwa Quids Betel Quids

Incidence of cervical cancer in Taiwan, 1979-2000

0

10

20

30

40

50

60

70

1979

1980

1981

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

年齡標準化發生率 粗發生率

6

Mortality of cervical cancer in Taiwan, 1995-2000

8.0

8.2

8.4

8.6

8.8

9.0

9.2

9.4

9.6

9.8

10.0

10.2

1995 1996 1997 1998 1999 2000

年齡標準化死亡率 粗死亡率

Is Mortality Reduction Attributed to Pap Smear Screening ?

0.0

0.2

0.4

0.6

0.8

1.0

0 2 4 6 8 10 12 14

治療後時間(年)

存活率

曲線B 基隆地區

(未篩檢前)

篩檢早期發現 y%曲線A歐美國家(預期目標)

子宮頸癌篩檢未來預期達到目標

醫療科學進步 + 初級預防

7

Ages:45-49Dense Breasts ?緻密乳房?

Taiwan

Age-specific incidence rate for breast cancer in Seoul, Korea, during 1992-1995

Age20 30 40 50 60 70 80 90

Inci

denc

e (p

er 1

00,0

00)

0

10

20

30

40

50

60

70

8

Mass Screening

Cons: Low incidence rate-Costly

Pro: Gain more life years—More production

多重預防政策(初段預防vs次段預防)之抉擇

9

Effects on Blood Pressure of Reduced Dietary Sodium and

the Dietary Approaches to Stop Hypertension (DASH) Diet

Sacks, Frank M.; Svetkey, Laura P.; Vollmer, William M. et al

The New England Journal of MedicineVolume 344(1) , 4 January 2001, pp 3-10

Example of Randomized Trial(Two-Factor Design)

高血壓健康促進(初段預防)

Study Design412 participants

Random Assignment

Control Group DASH Group

1. High

2. Intermediate

3. Low

1. High

2. Intermediate

3. Low

Sodium level

Measurement

RCD (Parallel Design)

Crossover Design

10

Systolic Blood Pressure (Panel A)

Diastolic Blood Pressure (Panel B)

The Effect of Reduced Sodium Intake and the DASH Diet

高血壓篩檢(次段預防)

11

子宮頸癌防治

• 子宮頸抹片篩檢

• 人類乳突病毒(HPV)篩檢

• 人類乳突病毒(HPV)疫苗

疾病自然史之複雜性

12

Initial Drug Therapy

Two-drug combination for most (usually thiazide-type diuretic and

ACEI or ARB or BB or CCB)

Thiazide-type diuretics for most. May

consider ACEI, ARB, BB, CCB,

or combination.

No antihypertensiveDrug indicated

Without Compelling

indication

or >=100

or 90-99

or 80-89

And <80

DBPmmHg

Yes>=160Stage 2Hypertension

Drug(s) for the compelling indications.

Other antihypertensiv

e drugs(diuretics,

ACEI, ARB, BB,CCB) as

needed.

Yes140-159

Stage 1Hypertension

Yes120-139

Pre-hypertension

Drug(s) for compelling indications.

Encourage<120Normal

With Compelling

Indications

Life StyleModification

SBPmmHg

BPClassification

Classification and management of blood pressure for Adults (JNC7)

ACEI: angiotensin converting enzyme inhibitor ARB:angiotensin receptor blocker

BB: beta-blocker CCB:calcium channel blockerFrom The Seventh Report of the joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Natural History of Hypertension

Normal Pre-hypertension Stage 1 Stage 2(SBP 120-139 orDBP 80-89)

(SBP 140-149 orDBP 90-99)

(SBP >=160 orDBP >=100)

13

Screening trial results•Breast cancer is a dynamic, progressive disease

20-mo later Additional 25-molater

Breast cancer is a progressive disease

Preclinical, detectable phase

Sojourn time

Mammographically detectable

Clinically detectable

14

Sojourn Time and Screening with Mammography

Normal

BiologicalOnset Screen-

detectable

Mammography

ClinicalPhase

Delay Time

Lead Time

The longer the delay time is, the smaller the benefit of breast cancer screening in mortality reduction

Sojourn Time and Early Detection with Various Screening Methods

PhysicalExamination

CurableStage

Normal

BiologicalOnset Screen-

detectable

ClinicalPhase

Mammographyor Sonography

Breast self-examination

15

Oral Pre-malignancy: Leukoplakia, Erythroleukoplakia, and Erythroplakia(Bouquot 1994)

Disease progression of Oral Pre-malignancy remains unclear

Sojourn Time and Screening with Dental Inspection +Toluidine Blue Test

Normal BiologicalOnset Screen-

detectable

Delay Time

Lead Time

The longer the delay time is, the smaller the benefit of oral cancer screening in mortality reduction

Dental Inspection + TB Test

Symptomatic Oral Cancer

16

Sojourn Time and Early Detection with Various Screening Methods

CurableStage

Normal

BiologicalOnset Screen-

detectable

Untrained Health Worker examination

Betel Qudis, Smoking, and Alcohol

Genetic Suspectibility

Dental Inspection + TB Test

Symptomatic Oral Cancer

多重篩檢工具之選擇

17

Multiple Screening Modalities篩檢方法

• Breast Self-examination (BSE)

• Physical Examination (PE)

• Mammography (1965-)

• Sonography (1990-)

• MRI (High Risk Group) (1995-

The relative benefit of downwards stage shifting早期發現的效益

• 95 % of the mortality benefit originates from downwards stage shifting of invasive breast cancers.

5 %

DCIS

95 %

Eur J Cancer. 2003 Aug;39(12):1746-54

18

Relevance of technological innovations拜科技進步之賜…

(2) Ultrasound Screening 乳房超音波篩檢

Medullary arcinoma, 7mm in size,

regular margins外緣呈規則狀的7釐米

大小髓狀弓形

Infiltrating ductalcarcinoma, 8mm in

size, irregular margins

外緣不規則狀的8釐米大小的浸潤管癌

Using Sonography to Screen Women with Mammographically Dense Breasts

19

Using Sonography to Screen Women with Mammographically Dense Breasts以乳房超音波篩檢緻密性乳房

• 67-year-old woman with dense Breast Imaging Reporting and Data System (BI-RADS) [14] category 3 breast tissue.• A and B, Mediolateral oblique (A) and craniocaudal (B)

screening mammograms reveal no abnormalities.• C, Screening sonogram shows solid hypoechoic mass that

measures 9 mm wide by 5 mm high. Angular margins (arrows) between mass and surrounding tissues are suspicious for malignancy. Sonographically guided biopsy (not shown) revealed invasive ductal carcinoma.

• D and E, Right mediolateral (D) and right craniocaudal (E) mammograms obtained after sonographically guided wire localization show uniformly dense breast tissue with no evidence of mass in hookwire area.

(3)Magnetic Resonance Imaging (MRI)

High-risk Group

20

182/258(70.5)176/251(70.1)6/81( 7)176/177(99.4)Mammography, clinical examination, and MR

乳房攝影術, 醫師觸診及核磁共振

188/258(72.9)167/277(73.6)21/81(26)167/177(94.4)MR imaging 核磁共振

183/258(70.9)165/229(72.4)18/81(22)165/177(93.2)Mammography, clinical examination, and US

乳房攝影術, 醫師觸診及乳房超音波

181/258(70.2)162/224(72.3)19/81(23)162/177(91.5)Mammography and US乳房攝影術及乳房超音波

175/258(67.8)147/200(73.5)28/81(34)147/177(83.0)Ultrasound (US) 乳房超音波

164/258(63.6)89/ 95(94.0)75/81(92)89/177(50.3)Clinical examination 醫師觸診

195/258(75.6)137/160(85.6)58/81(72)137/177(77.4)Mammography and Clinical examination

乳房攝影術及醫師觸診

181/258(70.2)120/140(85.7)61/81(75)120/177(67.8)Mammography 乳房攝影術

Accuracy正確性

Positive Predictive

Value陽性預測值

Specificity精確度

Sensitivity敏感度

Modality 診斷模組

Diagnostic Performance in 258 Proven Lesion不同診斷模組於258例確診個案之工具正確度

(177 Malignancies and 81 Benign Lesion)(177例惡性腫瘤 81例良性診斷) Berg WA, et al. Radiology 2004; 233

ROC curve indicator

Sen/(1-Sp)=2.71

Sen/(1-Sp)=1.19

篩檢，轉介及臨床人力供需之考量

21

Shortage of Health Manpower associated with Preventive Care

S 1 P 2 P 1

Q 1 Q 2 Q 3 Q /T Q uantity

Pric

e

S 2

D 2

D 1

社區健康平台（CHP）以整合式篩檢（CIS）為先驅

國家衛生政策˙子宮頸癌篩檢˙成人健檢

轉介及照護系統˙糖尿病照護網˙癌症防治中心

學術界合作

財務及經費支援˙篩檢Start-up成本˙轉介及治療成本

資訊系統Information System

˙健保IC卡實施˙國家癌症登記制度˙全民健保資料

社區資源可利用度˙社區健康營照˙鄰里組織˙志工與義工˙民眾知識水準提昇

醫療資源分佈˙醫師及專科醫師人力分佈˙醫院型態分佈

整合式篩檢可行性因素

行政組織變化及支持度 行政組織變化及支持度

行政組織變化及支持度 行政組織變化及支持度

22

篩檢決策之經濟評估

Disease process of cervical cancer including HPV infection (JAMA 2002)

23

Incremental cost-effectiveness (efficiency frontier) of 18 screening strategies

Cost-effectiveness analysis of vaccination in the setting of current screening in the US

24

Pap smear screening +HPV vaccination (1)

Vaccination may permits a later age of screening initiation and a less frequent screening interval

篩檢決策之實證醫學

25

Decision Making for Periodic Breast Cancer Screening (Risk, Benefit, and Limitations)

• 35-50歲婦女如何定期進行乳癌篩檢• 篩檢方法選定• 篩檢間隔• 遺傳諮詢評估 (Genetic Counseling)• 臨床諮詢 (Clinical Consultation)• 成本效益(Cost-effectiveness)如何?

• 50歲以上婦女如何定期進行乳癌篩檢方法選定• 篩檢間隔決定• 臨床諮詢 (Clinical Consultation)• 成本效益(Cost-effectiveness)如何?

RCT results for breast screening

Overall, 20% reduction in breast cancer mortality associated with invitation to screening mammography

Relative risk - log scale.5 1 1.5

Combined

Gothenburg

NBSS2

NBSS1

Stockholm

Edinburgh

Two-county

Malmo

HIP

0.80 (0.73, 0.86)

0.79 (0.58, 1.08)

1.02 (0.78, 1.33)

0.97 (0.74, 1.27)

0.90 (0.63, 1.28)

0.78 (0.62, 0.97)

0.68 (0.59, 0.80)

0.78 (0.65, 0.95)

0.78 (0.61, 1.00)

RR (95% CI)

Combined

Gothenburg

NBSS2

NBSS1

Stockholm

Edinburgh

2-county

Malmo

HIP

Hetero, p=0.21

26

Part II

整合性預防保健服務評價指標之建立

社區整合式篩檢評估指標發展方法

•結構面(Structure Dimension)•流程面(Process Dimension)•結果面(Outcome Dimension)

結構(Structure)

流程(Process)

結果(Outcome)

第一面向

第二面向

第三面向

整合式社區篩檢評估指標及系統建立

27

Figure 2. The Infrastructure and workflow of Building-Up Information System for Multiple Screening

Pre-Screening Phase Screening Phase Post-Screening Phase

Input

MortalityRegistry

PopulationRegistry

CancerRegistry

NHI*data

Pap SmearScreeningRegistry

PrimaryData fromScreening

P roc e s s Ou tp u t

Data Linkage andFiltering

Input P roc e s s

Update Information andClassificated Insurance Data

Registration

Blood Drawing

QuestionnaireInterview

FOBT Test

AnthropometryMeasurement

DentalExamination

Uric Test

Ou tpu t

Biochemical Data

Risk Factor Survey

Biochemical Data

Biochemical Data

PhysiologicalMeasruement

Dental HealthCheckup

*: National Health Insurance

Realtime Update

High RiskGroup

AbnormalFinding

Abnormal Findingand Serum Storage

AbnormalFinding

SelectedInvitation Listby Household

in EachCommunity

Parish

Attendantsof

Screening

HouseholdVerify

AbnormalFinding

AbnormalFinding

Input P ro c e s s

SurveillenceData

ClinicalOutcome

LongitudinalFollow-upConsultation

ConfirmedDiagnosis

SampleProcessing

Ou tpu t

AutomatedeligibleSubjects

Sources of Invited Population

Infrastructure of CIS

Infrastructure of CIS

整合式篩檢結構面指標次層面(Sub-dimension)

•篩檢人力及設施

•衛生教育促進之人力及設施

•立即轉介及照護人力

•實施衛生教育模式設計及人力

•行政資源運用

•資訊設施及人力

•計畫評估之人力

28

整合式篩檢流程面指標次層面

•涵蓋率邀請率及篩檢率

•執行期間各項執行之流程評估

•各項目完成率，轉介率及併發症發生率

A population-based, randomized controlled trial

Initiated by the Swedish National Board of Health and Welfare

The Swedish Two-County (W-E) Trial

29

W

E

● 25-year experience with mammographic screening:

what have we learned?

30

The Swedish Two-County (W-E) Trial

To assess the effect of invitation tomammography screening on breast cancer mortality in women aged 40 - 74 years

Published extensively in peer-reviewed journals (Lancet, i, 829, 1985)

The Swedish Two-County Trial

slide # 52

Number of women in the W-E trialInvited and control groups

Number of women in the W-E trialInvited and control groups

40 - 49 19 844 15 604 35 448

50 - 74 57 236 40 381 97 617

40 - 74 77 080 55 985 133 065

Age Invited Control Total

31

Attendance rates (%)W-E trial

1st 2nd 3rdAge screen screen screen

40 - 49 93 89 8850 - 59 92 88 8660 - 69 88 81 7870 - 74 79 67 -

Number of women with breast cancerAge 40 - 74 years at randomization. W-E trial

Age Invited Control Total

40 - 49 256 162 418

50 - 74 1 170 880 2 050

40 - 74 1 426 1 042 2 468

32

整合式篩檢結果面評估指標各次層面

• 服務結果面指標• 等候時間、篩檢時間、服務態度及整體滿意度• 可近性、可用性

• 篩檢成效短程指標• 計畫敏感度及精確度• 早期臨床症狀(如癌症期別) • 陽性及陰性預測值

• 篩檢成效中程指標• 盛行率/發生率• 篩檢間隔個案發生率/發生率

• 篩檢成效長程指標• 死亡率及發生率降低

• 篩檢經濟指標• 增加成本效果比(Incremental cost-effectiveness ratio)• 成本效益比值及差值

Screening for High-risk Women with Sonography(Hou MF et al 2002)

Target population: Female relatives of breast index cases (n=935)( Pre-menopause:62%)

Sensitivity Sonography:90%(19/21)Mammography:52%(11/21)Physical Examination:33.3%(7/21)

Sonography may be adequate for high-risk or pre-menopause women(Dense Breast)

33

Mammography Screening in Young Women is Controversial年輕婦女乳房攝影篩檢效益仍存在爭議性

• Poor Sensitivity due to Dense Breast Tissue

緣於緻密性乳房之低敏度度偵測

• Rapid Progression due to Preponderance in certain tumour type i.e. Medullary Breast Cancer

緣於特定腫瘤型態之乳癌進程快速-如髓狀乳癌

Aged 40-49

38%

68%

0%

20%

40%

60%

80%

100%

0--11 12--23

Time since previous screening (months)

Aged 50-69

13%

29%

45%

0%

20%

40%

60%

80%

100%

0--11 12--23 24+

Time since previous screening (months)

High interval cancer rates in women aged under 50 (Dense Breast)50歲以下婦女(緻密乳房)有較高的篩檢間隔乳癌發生

34

Distribution of malignancy gradeTumor size 1 - 9 mm, WE-trial

Age Grade 1 & 2 (%) Grade 3 (%)

40 - 49 80.9 19.150 - 59 85.1 14.960 - 69 88.1 11.9

Distribution of malignancy gradeTumor size 10 - 14 mm, WE-trial

Age Grade 1 & 2 (%) Grade 3 (%)

40 - 49 70.0 30.050 - 59 73.9 26.160 - 69 75.8 24.2

35

Distribution of malignancy gradeTumor size 15 - 19 mm, WE-trial

Age Grade 1 & 2 (%) Grade 3 (%)

40 - 49 46.2 53.850 - 59 69.4 30.660 - 69 62.0 38.0

Distribution of malignancy gradeTumor size 20 - 29 mm, WE-trial

Age Grade 1 & 2 (%) Grade 3 (%)

40 - 49 45.2 54.850 - 59 47.9 52.160 - 69 51.1 48.9

36

Cumulative 20-yr survival of 2,468 women (age 40-74)with DCIS and invasive breast cancer by tumor size

.0

.2

.4

.6

.8

1.0

0 5 10 15 20+

DCIS (6 / 169)1 - 9 mm (30 / 354)10 - 14 mm (67 / 498)15 - 19 mm (98 / 461)20 - 29 mm (182 / 534)30 - 49 mm (152 / 295)50+ mm (116 / 152)

RR 1.58 (1.03 - 2.43)RR 1.0RR 0.41 (0.17 - 0.98)

RR 19.00 (12.70 – 28.43)

DCIS1-14 mm invasive

an improvement which could not have been accomplished by any specific therapy or combination of therapeutic methods.

• The outcome was equally poor, regardless of the therapy chosen (NSABP B06)

Fisher B et al:N Engl J Med. 2002 Aug 22;3478567-75.

37

Cumulative mortality in ASP and PSP for age 40-49 and 50+, the Swedish Two-County Trial

瑞典雙郡試驗中40-49歲與50歲以上，篩檢組與未篩檢組之間累積死亡之比較

0

100

200

300

400

500

600

700

800

0 2 4 6 8 10 12 14+

Time (years)

Incidenc

ASP

PSP

40-49(small benefit) 50-69(large benefit)小效益 大效益

0

50

100

150

200

250

300

0 2 4 6 8 10 12 14

Time (years)

Mortality (per 100,000)

ASP

PSP

Randomized Trial of Breast Self-Examination(BSE)

in Shanghai: Final Results

38

Cumulative breast cancer deathsWomen aged 40 – 74 years, W-E trial

: The Difference Between Time Frame and Analytic Frame

0

200

400

600

800

0 5 10 15 20+

Control

Invited

0

200

400

600

800

0 5 10 15 20+

Control

Invited

(2) RR 0.68 (0.59 – 0.80)

Years since randomization

1977 1981

(1) Lead-time bias

Time Frame (2)

Time Frame (1)

Analytic Frame