临床研究中的统计学简介

Control

Aim : To ensure the comparability Classification according to design

Concurrent randomized control Before-after control / cross-over control Matching control Non-randomized control Historical control

Classification according to intervention measures

Placebo control Effective control
Blinding



Masking the identity of the assigned interventions Aim: to avoid potential bias caused by conscious or subconscious factors Classification:
样本参数 研究目的/结局指标
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Clinical trial sample calculation output
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Bias and Error
Bias and Error

Systematic Error or Bias: unknown or unacknowledged error created during the design, measurement, sampling, procedure, or choice of problem studied
Secondary Research
Analytic

Cross-sectional Case report Case series Ecological study Surveillance

Meta analysis System review Non-system review Comments Guidelines Decision-making analysis Economics analysis

All students (18 and over) Urban area only Han ethnicity Stroke patients/ whole population Etc.

Can you sample the entire population? -Census
Convenience sample Purposive sample Quota

Non-Probability Samples

Population and sample
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Sample Size – eg. two groups RCT
N
[ z1 / 2 2 p(1 p) z1 p1 (1 p1 ) p2 (1 p2 ) ]2 ( p1 p2 ) 2
Randomized control trial
Non-Randomized control trial
Cohort study
Generate hypothesis
Case-control study
Test hypothesis
Strength of Study Design: The Evidence Pyramid
p1: proportion in treatment group p2: : proportion in control group p: average of P1and P2, p=(p1+p2)/2；
α: Probability of Type I error, when α=0.05, Z1-α/2 =1.96; when α=0.01, Z1-α/2 =2.58；
Outline

Study design

Study design methods Clinical trial Sampling Bias and Error Reliability and Validity Data Types Statistical significance Appropriate statistical tests and result interpretation

Single blind: patient Double blind: patient + investigator Triple blind: patient + investigator + statistician
How to Blind Patients
Placebo

pill of same size, color, shape as treatment
Introduction of Biomedical Statistics in Clinical Research
Jiang Yong MD, MPH, PhD Clinical Trial Research Center, Beijing Tiantan Hospital, Capital Medical University

Categorical


Continuous

Nominal

Gender Male, Female Ever diagnosed hypertension Yes, No, Unsure
Body Mass Index (BMI) Number of drinks Number of offspring's Obesity percentages Fasting blood glucose


Simple random sample Systematic sample Stratified random sample

Proportionate Disproportionate – Proportion Probability to Size (PPS)

Cluster sample Multistage sample
Find the highest strength of evidence available to answer your clinical question.
Study Design


Selecting the “Best” study design Factors that must be considered


Tossing a coin Random number table

Computerized random number generator (SAS/Excel/…) Using blocking and/or stratified randomization to avoid imbalance

Validity



Reliability vs. Validity

Bias affects accuracy Variability affects precision
Introduction of Basic Biostatistical Methods
Data types
β: Probability of Type II error, power=1-β. When β=0.10, Z1-β =1.282。
Proportions – Two Independent Proportions – Tests using Proportions
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Parameters - Run
Reliability and Validity

Reliability


The extent to which a test is repeatable and yields consistent scores Affected by random error/bias The extent to which a test measures what it is supposed to measure A subjective judgment made on the basis of experience and empirical indicators Asks "Is the test measuring what you think it’s measuring?“ Affected by systematic error/bias

Sources of bias in an un-blinded study must be considered
Sampling

What is your population of interest?

To whom do you want to generalize your results?

The sampling frame is the list from which the potential respondents are drawn

Residents list Yellow book

Telephone book
Types of sampling methods

Probability Samples
Sampling

Why sample?

Limited resources (time, money) and workload Some destructive or invasive

Gives results with known accuracy that can be calculated mathematically
Randomization method


Aim: to ensure the comparability of each groups Maximize statistical power Minimize selection bias Minimize allocation bias (or confounding) Methods:

Error tends to go in one direction

Examples: Selection, Recall, Social desirability

Random/ sampling error

Unrelated to true measures

Example: Momentary fatigue

Introduction of Biostatistical Methods


How to work with statistician
Study design
Clinical Research Methods
Original Research
Observational Descriptive Experimental
sham operation sham device such as sham acupuncture

源自文库
Can Blinding Always be Done?

In some studies it may be impossible (or unethical) to blind



a treatment may have characteristic side effects difficult to blind the physician in a sometime not ethical

Resources: $ cost-effective Man power Time Ethnic problems Patient burden
Clinical trial -basic principals


Randomization Random sampling – representative, generalization Random grouping – comparability Control Blinding