assist.prof.sakda arj-ong vallibhakara, m.d., phd....3. study design 4. participants & setting...

Assist.Prof.Sakda Arj-Ong Vallibhakara, M.D., PhD. MSIT, MA.(Information Science) Pediatrics, Pediatric Cardiology

Cert. Intervention Cardiology Emergency Medicine, Cert.PEM (NCH, OSU)

E-mail: [email protected]

Tel: 0-2201-1284

Research

Good Question ?

Require Research ?

Methodology ?

Population ?

Measurement

?

Design

STOP !!!

S T A T I S T I C S

1. Background & Rationale 2. Literature review 3. Study design 4. Participants & setting 5. Statistics : eg randomisation (if RCT) 6. Data collection 7. Data management 8. Ethic consideration 9. Budget 10. Time table

What is the problem? ◦Magnitude of problem: prevalence,

incidence, mortality rate

How is it burden once it occurs? ◦ Disability, cost of treatment for individual

and/or country levels, QoL

What are evidences already available?

Why do we need further evidences (Gap of Knowledge) ◦ Previous studies did not answer the

question? ◦ Limitation of previous studies: Poor

methodology? ◦ No previous study

How can we do better? Me too Research, Modified What new evidence will be added? (Try to convince funding agency/IRB as

much as possible)

Most common cancer in Thai women

Age standardized incidence rate = 20.9 per 100,000 women in year 2010

Cancer in Thailand volume IV 1998-2000. National Cancer

Institute; 2007

Advanced stage

breast cancer

5 year survival rate = 27.1% 5 year survival rate = 98.1%

Early stage breast

cancer

Screening

Mammogram

Clinical breast examination

Self breast examination

56% of patients presented at stage III and IV

Lack of self awareness

The scarcity of mammographic facilities

279 diagnostic radiologists

(236,559 คน : 1 Radiologist)

13 provinces had no radiologist

(17 % lack of )

Weerasak P et al. Regional Helath Forum: Volume 8(1), 2004

All women Regular screening with

MMG

MMG regular

screening

High risk

Low risk

Breast cancer risk prediction

model ??

Me too research ???

?

There are many breast cancer risk prediction models

?

Low performance because of lack of important risk factors ? In Asian population ?

To build up breast cancer risk prediction model in Thai women

Increase model performance because we will consider the new important risk factors of breast cancer in the model

P= patient I= intervention /exposure/ study factor C = Comparator O = Outcome

Feasible Y/N Novel ◦ New finding ◦ Confirms or refutes previous finding ◦ Extend

Ethics Relevant ◦ To biological rationale

Locate relevant studies as many as possible ◦ Medline, PubMed, EMBASE, Scopus, EndNote ◦ Create search strategies : “Breast CA AND

Screening” Critical appraisal of previous studies Systematic review ◦ Disease mechanism ◦ Management ◦ Prognosis ◦ Outcome ◦ Previous evidences

Summarization of research methods

Study design

Variables and Measurements

Presenting results

Still needs answer for these RQ?

Limitation of previous studies

Know the gap of knowledge

“Plan to do better”

Conceptual frame work

1. Background & Rationale 2. Literature review 3. Study design (Methodology) 4. Participants & setting 5. Statistics : eg randomisation (if RCT) 6. Data collection 7. Data management 8. Ethic consideration 9. Budget 10. Time table

Should be address: Methodology and Design study eg. ◦RCT ◦Cohort study ◦Case-control study ◦Cross-sectional study ◦Descriptive study

Did investigator Assign exposure ?

Experimental Study Observational Study

Random/Allocation ? Comparison group ?

RCT NonRCT

Analytical Study

Descriptive Study

Direction ?

Cohort Study Case control Study Cross-sectional Study

E O O E E = O

(Same time)

Yes

Yes

Yes Yes Yes

Yes

No

No

No

Percent %, incidence prevalence

P value

95 %CI

Odds Ratio

RR, ARR, RD

NNT etc..

1. Background & Rationale 2. Literature review 3. Study design (Methodology) 4. Participants & setting 5. Statistics : eg randomisation (if RCT) 6. Data collection 7. Data management 8. Ethic consideration 9. Budget 10. Time table

◦Eligibility criteria: Inclusion Exclusion

◦Setting & period of study

Cross-sectional study

Ramathibodi hospital

September 2011-September 2012

Internal validation

External validation

Use the same data set of development phase

Splitting data 70:30

Bootstrap technique with 10,000 repetitions


National Cancer Institute in Bangkok

Songklanagarind hospital

Ages ≥ 18 years who come to screen breast cancer with MMG

Can listen and well understand Thai language

Willing to participate and signed inform consent

Example of RCT

For observational studies

Describe all interested variables ◦ Study factors

◦ Co-variables

How/when to measure ?

Are they varied or static ?

How many times will they be measured ?

Date of birth

Living place

Educational levels

Underlying disease such as HT, DLP, CKD, DM

DM; age at diagnosis, types of treatment

Weight

Height

BMI

FH of breast cancer

(Next….Domain & Definition of Variable)

Age at menarche

Marital status

Menopausal status

- Premenopause

- Postmenopause

- Unknown menopausal status

Age at menopause

Age at birth of first child

Parity

History of breastfeeding

- Duration of breastfeeding in each child

History of OCs used

-ever, never

- Age at first use

- Age at last use

- Duration of use

- Current user, past user

History of HRT used

- ever, never

- Type of HRT

- Age at first use

- Age at last use

- Duration of use

- Current user, past user

Active smoker

Passive smoker

Non smoker

Ever/never (0/1)

- women ever drunk alcohol > 3/week for

6 months

Dose response relationship

- type of alcoholic beverages

- amount of alcohol/day

Primary outcome

- All histological types of invasive breast cancers

Department of pathology, department of hospital statistics

Pathologic data will be linked with mammographic data

Describe how sample size is estimated For hypothesis testing (comparative study) ◦ Type I & II error ◦ Size of detectable

Minimum size that expect or should be a clinical significance

◦ Basic information Information in control group

Mean (SD) headache score in control LV size in conventional haemodialysis group Cure rate in standard treatment Median time to success (viral load < 50 copies/ml) in Efavirenz 600

mg (control) Size of studied population (feasibility of recruitment)

◦ For RCT Interim analysis (How many time ?, adjusting for multiple test ) Stopping rule

Required information ◦ Previous studies reported 50% of infectious

complications

Set ◦ 80% statistical power (20% type II error) ◦ Type I error= 0·05 ◦ Ratio Treatment: placebo = 1:1 ◦ Wish to reduce infectious complication rate

at least of 20%

200 patients with predicted severe acute pancreatitis

Data record form (DRF or CRF) ◦ Include only relevant variables into the form

◦ Make sure that what you are going to record is appropriate and will be able to analyse and answer your research question

◦ Record variables as their actual measurement Time duration: date start, date end

Age: birth date to current date

BMI: height, weight

DM, HT, Dislipidemia: BS, BP, Cholesterol

Help to Label

Help to Cleansing

Domains:-

Demographic Clinical

Scoring/Scaling

Laboratory

Treatment ( Medications , Op vs.Non-Op)

AE

Outcome

For follow-up study, ◦ What variables are constant and varied over time

Enrollment form

Contains all variables

Sequence & groups

Follow-up

Time varying variables

Outcome assessments

◦Database Data : qualified CRF

Data quality control

Data cleaning

Software used

How to entry

Data checking & validating

3 parts: demographic data, reproductive data, outcome data

Standardized interviewer

DMU: section of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital

Invite participant

Complete DRFs

DRFs sent to DMU

Check completeness and validity

Register and store

Check completeness

DRFs scanned with OMERET

2 persons verify data

Security

- data scanner, data manager, PI

- Confidential data will be encrypted

Cleaning and checking data: once a month

Back up

- every week

- multi-session technique in optical disc

1. Background & Rationale 2. Literature review 3. Study design 4. Participants & setting 5. Statistics (Data Analysis) 6. Data collection 7. Data management 8. Ethic consideration 9. Budget 10. Time table

Describe all detail what statistics are going to apply for?

Descriptive statistic

Analytic statistics

Software used (SPSS, STATA, SAP, R) Level of significance (P < 0.05, 95 %CI)

Categorical data

- Frequency and percentage

- Chi-square test (Fisher exact test)

Continuous data

- Mean with SD, or median with range

- t-test (Mann-Whitney)

Model selection:-

Simple logistic regression

- P value < 0.10

Multiple logistic regression

- Backward elimination

Goodness of fit

- Hosmer-Lemeshow Chi square test

Calibration

- E/O ratio

Discrimination

- C statistic

Model diagnostic

Residual chi square and residual deviance

Outliers

- predicted values

- estimated coefficient

- DRF will be checked and verified

- data will be considerate to drop out

Inquiry from collaborative site **

Imputation method by STATA program version 11

2 sides test with P value < 0.05

Dummy tables Imagine how results will be reported Depends on study design Follow step of data analysis

Describe general characteristics of subjects

Compare general characteristics of

◦ Treatment/non-treatment in RCT

◦ Case/control in case-control

◦ Risk/non-risk in cohort

◦ Outcome +/Outcome – in Cross sectional study

Assessment of

Treatment effect in RCT,

Risk or prognostic effect in cohort, case-control, cross-sectional


Has no intervention or procedure ?

Interview ?

No expected harm or discomfort ?

Emotional feeling of sadness

Ethical approval from all collaborative sites

Inform consent Confidentiality - using code and encryption for

confidential data - assigned and authorized team members Comply under the law of human research

policy Compensation

◦Per-patient cost

◦Study-level cost

◦ Indirect cost (Intangible cost)

◦Total costs

◦Compensation cost

1. Background & Rationale 2. Literature review 3. Study design 4. Participants & setting 5. Statistics : eg randomisation (if RCT) 6. Data collection 7. Data management 8. Ethic consideration 9. Budget 10. Time table/Time Frame

Proposal phase Study-phase

Conducting study

Data management

Analysis

Writing

Reports Manuscripts

Publications

Task Time line Literature review July 2010-March 2011

Protocol writing April 2011-June 2011

Defend research proposal July 2011

Submit for ethical board review and approval

July 2011

Prepare team and data collection

August 2011-August 2012

Task Time line Training and visit site August 2011 –July 2012

Data entry September 2011-November 2012

Data analysis and conclusion

October 2012-December 2012

Report writing January 2013-Febuary 2013

Report submission March 2013

Activity

2009

2010

2011 Aug Sep Oct Nov Dec Jan Feb Mar Apr May June Jul Aug Sep Oct Nov Dec Jan Feb Mar

Enrollment

Data collection

Monitor and audit

CRF transferring

Data entry

Investigator meeting

Cleaning&checking data

Data analysis Enrollment Enroll + FU

Report

Manuscript I

Manuscript II

Study-phase

Transform to PICO

1. Background & rationale

2. Literature review 3. Study design 4. Participants & setting 5. Randomisation (if RCT) 6. Data collection 7. Data management 8. Ethic consideration 9. Budget 10.Time table 11.Reference 12.Acknowledgement 13.Tables 14.Figures 15.Appendices

Reference Acknowledgement Tables Figures Appendices ◦CRF/DRF ◦Dummy table ◦ Inform & Consent

Test 30 ข้อ จากทัง้หมดทกุหวัข้อ ◦ 70 % of attended ◦ 30 Items Randomly (15 Per Parts) ◦ 2 times then Pass/Not Pass ◦ Faculty Certification for EBM ◦ Send information to Ethics

Funding

IRB

Letter to Department

Duration : 15 Frbuary-15 March 2016

ไม่รวมภาษาองักฤษ Http://www.medmahidol.ac.th/ceb

Thank You

assist.prof.sakda arj-ong vallibhakara, m.d., phd....3. study design 4. participants & setting...

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