Introduction to theIntroduction to theStatistical AnalysisStatistical Analysisof the Clinical Trialsof the Clinical Trials

Main QuestionsMain Questions

1.1. The Clinical Trials BasicsThe Clinical Trials Basics

2.2. Importance of the Statistical MethodsImportance of the Statistical Methods

3.3. Major software solutionsMajor software solutions

4.4. STATISTICA BasicsSTATISTICA Basics

The Clinical Trials BasicsThe Clinical Trials Basics

What Are Clinical Trials?What Are Clinical Trials?

Research studies involving peopleResearch studies involving people

Try to answer scientific questions and Try to answer scientific questions and find better ways to prevent, diagnose, or find better ways to prevent, diagnose, or treat diseasetreat disease

Why Are Clinical Trials Why Are Clinical Trials Important?Important?

Clinical trials translate results of Clinical trials translate results of

basic scientific research into better ways to basic scientific research into better ways to prevent, diagnose, or treat diseaseprevent, diagnose, or treat disease

The more people take part, the faster we can:The more people take part, the faster we can:

- Answer critical research questions- Answer critical research questions

- Find better treatments and ways to prevent disease- Find better treatments and ways to prevent disease

What Are the Different Types What Are the Different Types of Clinical Trials?of Clinical Trials?

TreatmentTreatment

PreventionPrevention

Early detection/screeningEarly detection/screening

DiagnosticDiagnostic

Quality of life/supportive careQuality of life/supportive care

Treatment TrialsTreatment Trials

What new treatments can help people What new treatments can help people with a particular disease?with a particular disease?

What is the most effective treatment for What is the most effective treatment for people with that disease?people with that disease?

Clinical Trial PhasesClinical Trial Phases

Phase 1: 15-30 peoplePhase 1: 15-30 people– What dosage is safe?What dosage is safe?– How should treatment be given?How should treatment be given?– How does treatment affect the body?How does treatment affect the body?

Phase 2: Less than 100 peoplePhase 2: Less than 100 people– Does treatment do what it is supposed to?Does treatment do what it is supposed to?– How does treatment affect the body?How does treatment affect the body?

Clinical Trial PhasesClinical Trial Phases

Phase 3: From 100 to thousands of Phase 3: From 100 to thousands of peoplepeople– Compare new treatment with current standardCompare new treatment with current standard

Phase 4: From hundreds to thousands Phase 4: From hundreds to thousands of peopleof people– Usually takes place after drug is approvedUsually takes place after drug is approved– Used to further evaluate long-term safety and Used to further evaluate long-term safety and

effectiveness of new treatmenteffectiveness of new treatment

Clinical Trial DesignClinical Trial Design

Eligibility criteriaEligibility criteria: Can range from : Can range from general (age, gender, weight) to specific general (age, gender, weight) to specific (prior treatment, tumor characteristics, (prior treatment, tumor characteristics, blood cell counts, organ function); blood cell counts, organ function); eligibility criteria also vary with trial eligibility criteria also vary with trial phasephase– Varies with protocol and phasesVaries with protocol and phases

EndpointEndpoint: Measurable outcome that : Measurable outcome that indicates an intervention’s effectiveness indicates an intervention’s effectiveness

Clinical Trial DesignClinical Trial Design

RandomizationRandomization: A method : A method used to prevent bias in used to prevent bias in research; a computer or a research; a computer or a table of random numbers table of random numbers generates treatment generates treatment assignments, and assignments, and participants have an equal participants have an equal chance to be assigned to chance to be assigned to one of two or more groups one of two or more groups (e.g., the control group or the (e.g., the control group or the investigational group)investigational group)

Clinical Trial DesignClinical Trial DesignStratificationStratification: Categorizing subjects into subgroups : Categorizing subjects into subgroups

by specific characteristicsby specific characteristics– Enables researchers to look into separate Enables researchers to look into separate

subgroups to see whether differences existsubgroups to see whether differences exist

Clinical Trial ProtocolClinical Trial ProtocolA recipe or blueprintA recipe or blueprintStrict scientific guidelines:Strict scientific guidelines:

--Purpose of study--Purpose of study --How many people will participate--How many people will participate --Who is eligible to participate--Who is eligible to participate --How the study will be carried out--How the study will be carried out --What information will be gathered about --What information will be gathered about

participantsparticipants --Endpoints--Endpoints

2. Importance of the Statistical 2. Importance of the Statistical MethodsMethods

Appropriate statistical methods for Appropriate statistical methods for analysing trial data are critical for the analysing trial data are critical for the correct interpretation of the results. correct interpretation of the results. Item 12 of the CONSORT (Item 12 of the CONSORT (Consolidated Consolidated Standards Of Reporting TrialsStandards Of Reporting Trials) statement ) statement relates to the statistical methods used in relates to the statistical methods used in the reporting of trials, together with the reporting of trials, together with scientific and statistical principles scientific and statistical principles concerning analyses of subgroups, concerning analyses of subgroups, endpoints and appropriate statistical tests:endpoints and appropriate statistical tests:– http://www.consort-statement.org/http://www.consort-statement.org/

2. 2. Statistical Analysis plan Statistical Analysis plan

Specifying how the outcome will be measured. Specifying how the outcome will be measured. Common measures are: Common measures are:

Binary - event present or not.Binary - event present or not.

Count - the frequency of an event in a set time Count - the frequency of an event in a set time period.period.

Measurement on a continuous scale..Measurement on a continuous scale..

Other measurements include ordinal scales (eg, Other measurements include ordinal scales (eg, quality-of-life ratings, 5-point trauma scales) and quality-of-life ratings, 5-point trauma scales) and non-ordered scales (eg, patient preferences non-ordered scales (eg, patient preferences between oral, intravenous or combination between oral, intravenous or combination treatment delivery).treatment delivery).

2. Statistical Analysis plan2. Statistical Analysis plan

Any transformations on the data likely to be Any transformations on the data likely to be required before analysis. This includes required before analysis. This includes possible groupings or classifications of data possible groupings or classifications of data (eg, into good, acceptable and poor quality (eg, into good, acceptable and poor quality of life), as well as mathematical of life), as well as mathematical transformations (logarithms, square root, transformations (logarithms, square root, etc) needed to "normalise" the outcome etc) needed to "normalise" the outcome variables. variables.

2. Statistical Analysis plan2. Statistical Analysis plan

Appropriate statistical tests which will be Appropriate statistical tests which will be used to analyse the data. While the used to analyse the data. While the underlying assumptions of common underlying assumptions of common statistical tests vary, underpinning all these statistical tests vary, underpinning all these tests is the assumption that either the tests is the assumption that either the outcome or other calculated measures outcome or other calculated measures (such as correlation coefficients, hazard or (such as correlation coefficients, hazard or odds ratios) will be "normally" distributed. odds ratios) will be "normally" distributed.

3. 3. Major software solutions Major software solutions

Microsoft Excel / OpenOffice KSpreadMicrosoft Excel / OpenOffice KSpreadSPSSSPSSSTATISTICASTATISTICA MapleMapleMatLab and other more than 100 solutions MatLab and other more than 100 solutions listed there:listed there:– http://en.wikipedia.org/wiki/http://en.wikipedia.org/wiki/

List_of_statistical_packagesList_of_statistical_packages

4. STATISTICA Basics4. STATISTICA Basics

STATISTICASTATISTICA is a comprehensive, is a comprehensive, integrated data analysis, graphics, integrated data analysis, graphics, database management, and custom database management, and custom application development system featuring a application development system featuring a wide selection of basic and advanced wide selection of basic and advanced analytic procedures for business, data analytic procedures for business, data mining, science, and engineering mining, science, and engineering applications.applications.

4. STATISTICA Basics4. STATISTICA Basics

4. STATISTICA Basics4. STATISTICA Basics The The StatisticsStatistics menu provides menu provides access to all access to all available available analysis types analysis types within within STATISTICASTATISTICA..The The GraphsGraphs menu provides menu provides direct access to direct access to a variety of a variety of commonly used commonly used graph types graph types

4. STATISTICA Basics4. STATISTICA Basics

STATISTICASTATISTICA uses five principal document uses five principal document types:types:

WorkbooksWorkbooks

SpreadsheetsSpreadsheets (multimedia tables) (multimedia tables)

ReportsReports

GraphsGraphs

Macros (Macros (STATISTICASTATISTICA Visual Basic) Visual Basic)

4. STATISTICA Basics4. STATISTICA Basics Spreadsheets are based on StatSoft's proprietary Spreadsheets are based on StatSoft's proprietary multimedia table technology and are used to manage multimedia table technology and are used to manage both input data and the numeric or text output.both input data and the numeric or text output.

The basic form of the spreadsheet is a simple two-The basic form of the spreadsheet is a simple two-dimensional table that can handle a practically dimensional table that can handle a practically unlimited number of cases (rows) and variables unlimited number of cases (rows) and variables (columns), and each cell can contain a virtually (columns), and each cell can contain a virtually unlimited number of characters.unlimited number of characters.

Sound, video, graphs, animations, reports with Sound, video, graphs, animations, reports with embedded objects, or any ActiveX compatible embedded objects, or any ActiveX compatible documents can also be attached.documents can also be attached.

4. STATISTICA Basics4. STATISTICA Basics

4. STATISTICA Basics4. STATISTICA Basics The spreadsheet window comprises The spreadsheet window comprises several basic components.several basic components.

4. STATISTICA Basics4. STATISTICA Basics Workbooks are the default way of  managing output. Workbooks are the default way of  managing output. They store each output document (e.g., a They store each output document (e.g., a STATISTICASTATISTICA Spreadsheet or Graph, as well as an Microsoft Word or Spreadsheet or Graph, as well as an Microsoft Word or Excel document) as a tab.Excel document) as a tab.

Adapted from a slide presentation developed by the National Adapted from a slide presentation developed by the National Cancer Institute, for its Cancer Clinical Trials Education Series.Cancer Institute, for its Cancer Clinical Trials Education Series.