1. Introduction to the Statistical Analysis of the Clinical Trials
Whether you have <insert condition>, are a friend or family member of someone with <insert condition>, or someone who works with people with people who have <insert condition>, this presentation will help answer some of the most important questions you may have about clinical trials.  
The presentation will include a discussion about:
Why clinical trials are important
How clinical trials work
How clinical trials advance patient care
How participants are protected
Some of the barriers to participating in clinical trials
And finally, I’ll talk about ways you can find clinical trials in your community.

2. Main Questions The Clinical Trials Basics
Importance of the Statistical Methods
Major software solutions
STATISTICA Basics
Clinical trials are research studies involving people. Clinical trials are the final step in a long research process that includes preliminary laboratory research and animal testing.
Clinical trials try to answer specific scientific questions to find better ways to prevent, detect, or treat diseases, or to improve care for people with diseases.
In cancer research, for example, a clinical trial is designed to show how a certain anticancer approach—for instance, a promising drug, a new surgical procedure, a new diagnostic test, or a possible way to prevent cancer—affects the people who receive it.

3. The Clinical Trials Basics
What Are Clinical Trials?
Research studies involving people
Try to answer scientific questions and find better ways to prevent, diagnose, or treat disease
Clinical trials are research studies involving people. Clinical trials are the final step in a long research process that includes preliminary laboratory research and animal testing.
Clinical trials try to answer specific scientific questions to find better ways to prevent, detect, or treat diseases, or to improve care for people with diseases.
In cancer research, for example, a clinical trial is designed to show how a certain anticancer approach—for instance, a promising drug, a new surgical procedure, a new diagnostic test, or a possible way to prevent cancer—affects the people who receive it.

4. Why Are Clinical Trials Important?
Clinical trials translate results of
basic scientific research into better ways to prevent, diagnose, or treat disease
The more people take part, the faster we can:
- Answer critical research questions
- Find better treatments and ways to prevent disease
It is important to understand what clinical trials do to fight disease:
·         Clinical trials translate results of basic scientific research into better ways to prevent, diagnose, or treat disease.
·         Clinical trials contribute to knowledge and progress against disease. Many of today’s most effective treatments are based on previous study results. Because of progress made through clinical trials, many people treated for various diseases are now living longer.
·         The more people that participate in clinical trials, the faster we can answer the critical research questions that will lead us to better treatment and prevention options for a range of diseases.
     

5. What Are the Different Types of Clinical Trials?
Treatment
Prevention
Early detection/screening
Diagnostic
Quality of life/supportive care
There are at least 5 types of clinical trials:
1. Treatment trials seek to find out:
·         What new treatment approaches can help people who have a disease
·         What is the most effective treatment for people with that disease
2. Prevention trials seek to find out what approaches can prevent a disease from developing in people who have never had it
3. Early-detection/screening trials seek to discover new ways of finding a disease in people before they have any symptoms
4. Diagnostic trials seek to find out how new tests or procedures can better identify a disease in people when we think it is there
5. Quality-of-life/supportive care trials seek to find out what kinds of new approaches can improve the comfort and quality of life of people with a disease

6. Treatment Trials
What new treatments can help people with a particular disease?
What is the most effective treatment for people with that disease?
Most clinical trials are treatment trials. These clinical trials involve people who have a disease.
These studies try to answer specific questions about the effectiveness of a new treatment or a new way of using an existing treatment.

7. Clinical Trial Phases Phase 1: 15-30 people
What dosage is safe?
How should treatment be given?
How does treatment affect the body?
Phase 2: Less than 100 people
Does treatment do what it is supposed to?
Clinical trials take place in phases.
Once laboratory studies (in test tubes and animals) show that a new approach has promise, a phase 1 trial can begin. A phase 1 trial is the first step in testing a new agent (drug or compound) in humans.
In these studies, researchers look for the best way to give people the new agent (for example, by pill or by injection), how often it should be given, and what the safest dose is. These studies also include special laboratory tests such as blood tests and biopsies to evaluate how the new agent is working in the body.
In phase 1 trials, small groups of people with a disease are treated with a certain dose of a new agent that has already been extensively studied in the laboratory. The dose is usually increased group by group in order to find the highest dose that does not cause harmful side effects. This process determines a safe and appropriate dose to use in a phase 2 trial.
While the primary purpose of phase 1 trials is to find the safest dose of a new agent, researchers also evaluate whether the new agent benefits patients.
People with a disease who are eligible for phase 1 studies have no known effective treatment options, or they have already tried other treatment options. Many participate in these trials because they want to help others and contribute to research. Phase 1 trials usually have 15 to 30 participants.

8. Clinical Trial Phases Phase 3: From 100 to thousands of people
Compare new treatment with current standard
Phase 4: From hundreds to thousands of people
Usually takes place after drug is approved
Used to further evaluate long-term safety and effectiveness of new treatment
Phase 3 trials focus on learning how a new treatment compares to “standard treatment” (the most widely accepted treatment, based on results of past research). Researchers want to learn whether the new treatment is better than, the same as, or worse than the standard treatment.
In most cases, trials move into phase 3 testing only after a treatment shows positive results in phase 2 trials.   
In phase 3 trials, participants have an equal chance of being assigned to one of two or more groups (also called “arms”).
The process of assigning participants to groups is called randomization.
Many people choose to get their first treatment in a phase 3 trial. The type of participant varies, depending on the kind of question being asked about a particular disease. Phase 3 trials usually have hundreds to thousands of participants, in order to find out if true differences exist in the effectiveness of the treatments being tested.

9. Clinical Trial Design
Eligibility criteria: Can range from general (age, gender, weight) to specific (prior treatment, tumor characteristics, blood cell counts, organ function); eligibility criteria also vary with trial phase
Varies with protocol and phases
Endpoint: Measurable outcome that indicates an intervention’s effectiveness
Phase 3 trials are randomized clinical trials, and some phase 2 trials may also be randomized.
Randomization is a method used to prevent bias in research. Treatment assignments are generated by a computer, and each participant has an equal chance of being assigned to one of two or more groups, the control group and the treatment group:
The control group is made up of the people who get the most widely accepted treatment (standard treatment) for the disease
The investigational group is made up of the people who get the new treatment being tested.
The next slide illustrates how randomization works.

10. Clinical Trial Design
Randomization: A method used to prevent bias in research; a computer or a table of random numbers generates treatment assignments, and participants have an equal chance to be assigned to one of two or more groups (e.g., the control group or the investigational group)
Phase 3 trials are randomized clinical trials, and some phase 2 trials may also be randomized.
Randomization is a method used to prevent bias in research. Treatment assignments are generated by a computer, and each participant has an equal chance of being assigned to one of two or more groups, the control group and the treatment group:
The control group is made up of the people who get the most widely accepted treatment (standard treatment) for the disease
The investigational group is made up of the people who get the new treatment being tested.
The next slide illustrates how randomization works.

11. Clinical Trial Design
Stratification: Categorizing subjects into subgroups by specific characteristics
Enables researchers to look into separate subgroups to see whether differences exist
Phase 3 trials are randomized clinical trials, and some phase 2 trials may also be randomized.
Randomization is a method used to prevent bias in research. Treatment assignments are generated by a computer, and each participant has an equal chance of being assigned to one of two or more groups, the control group and the treatment group:
The control group is made up of the people who get the most widely accepted treatment (standard treatment) for the disease
The investigational group is made up of the people who get the new treatment being tested.
The next slide illustrates how randomization works.

12. Clinical Trial Protocol
A recipe or blueprint
Strict scientific guidelines:
--Purpose of study
--How many people will participate
--Who is eligible to participate
--How the study will be carried out
--What information will be gathered about participants
--Endpoints
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

13. 2. Importance of the Statistical Methods
Appropriate statistical methods for analysing trial data are critical for the correct interpretation of the results.
Item 12 of the CONSORT (Consolidated Standards Of Reporting Trials) statement relates to the statistical methods used in the reporting of trials, together with scientific and statistical principles concerning analyses of subgroups, endpoints and appropriate statistical tests:
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

14. 2. Statistical Analysis plan
Specifying how the outcome will be measured. Common measures are:
Binary - event present or not.
Count - the frequency of an event in a set time period.
Measurement on a continuous scale..
Other measurements include ordinal scales (eg, quality-of-life ratings, 5-point trauma scales) and non-ordered scales (eg, patient preferences between oral, intravenous or combination treatment delivery).
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

15. 2. Statistical Analysis plan
Any transformations on the data likely to be required before analysis. This includes possible groupings or classifications of data (eg, into good, acceptable and poor quality of life), as well as mathematical transformations (logarithms, square root, etc) needed to "normalise" the outcome variables.
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

16. 2. Statistical Analysis plan
Appropriate statistical tests which will be used to analyse the data. While the underlying assumptions of common statistical tests vary, underpinning all these tests is the assumption that either the outcome or other calculated measures (such as correlation coefficients, hazard or odds ratios) will be "normally" distributed.
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

17. 3. Major software solutions
Microsoft Excel / OpenOffice KSpread
SPSS
STATISTICA
Maple
MatLab and other more than 100 solutions listed there:
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

18. 4. STATISTICA Basics
STATISTICA is a comprehensive, integrated data analysis, graphics, database management, and custom application development system featuring a wide selection of basic and advanced analytic procedures for business, data mining, science, and engineering applications.
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

19. 4. STATISTICA Basics
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

20. 4. STATISTICA Basics
The Statistics menu provides access to all available analysis types within STATISTICA.
The Graphs menu provides direct access to a variety of commonly used graph types
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

21. 4. STATISTICA Basics STATISTICA uses five principal document types:
Workbooks
Spreadsheets (multimedia tables)
Reports
Graphs
Macros (STATISTICA Visual Basic)
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

22. 4. STATISTICA Basics
Spreadsheets are based on StatSoft's proprietary multimedia table technology and are used to manage both input data and the numeric or text output.
The basic form of the spreadsheet is a simple two-dimensional table that can handle a practically unlimited number of cases (rows) and variables (columns), and each cell can contain a virtually unlimited number of characters.
Sound, video, graphs, animations, reports with embedded objects, or any ActiveX compatible documents can also be attached.
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

23. 4. STATISTICA Basics
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

24. 4. STATISTICA Basics
The spreadsheet window comprises several basic components.
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

25. 4. STATISTICA Basics
Workbooks are the default way of  managing output. They store each output document (e.g., a STATISTICA Spreadsheet or Graph, as well as an Microsoft Word or Excel document) as a tab.
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study.
Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial.
The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary.
Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

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