THE STUDY POPULATION

1. THE STUDY POPULATION • Basic Workshop on Randomized Controlled Trials. • Pragmatic Randomized Controlled Trials in Health Care - Practihc

2. OBJECTIVES • Defining population and sample • Describing the elements needed to defining the eligibility criteria of a RCT • Describing the effect of the eligibility criteria on the external validity of a trial • Describing strategies for an optimal recruitment of subjects

3. OBJECTIVES • Defining population and sample • Describing the elements needed to defining the eligibility criteria of a RCT • Describing the effect of the eligibility criteria on the external validity of a trial • Describing strategies for an optimal recruitment of subjects

4. BASIC CONCEPTS • Population: a group of individuals with a specific set of clinical, demographic, temporal and geographic characteristics • Target: all individuals to whom, according to the clinical and demographic characteristics, it is possible to generalize the study findings • Accessible: group of individuals who can be reached by the investigator (considering geographical and temporal factors) • Sample: group of individuals from the accessible population who participate in the study.

5. EXAMPLE OF A QUESTION In children between three months and five years hospitalized due to severe pneumonia (defined based on WHO criteria), is the proportion of failures at 48 hours of treatment with oral amoxicillin equivalent to that observed with injectable penicillin?

6. INFERENCE FROM STUDY SAMPLE TO THE POPULATION External validity Internal validity Question Target population Real study Final sample Planned study Desired sample Accessible population Children between 2m and 5y hospitalized in the world due to severe pneumonia Children seen in 9 centers of 8 countries. Children that fulfill criterion of selection Children whose parents agree to participate.

7. PURPOSES WHEN SELECTING THE STUDY SAMPLE • Ensuring that the study findings represent what truly happens in the population: • Representative sample to prevent systematic errors (more important in descriptive studies) • Adequate sample size to prevent random errors. • Use in the best possible way the resources available (and always limited) for research

8. OBJECTIVES • Defining population and sample • Describing the elements needed to defining the eligibility criteria of a RCT • Describing the effect of the eligibility criteria on the external validity of a trial • Describing strategies for an optimal recruitment of subjects

9. ELIGIBILITY CRITERIA • Clinical, demographical, geographical and temporal characteristics that define the individuals who participate in the study. • Reasons to make them explicit: • Allows selecting the sample of the study • Allows others (investigators or clinicians): • Reproducing the study • Assessing if the sample was appropriate for the research question • Identifying individuals to whom findings apply

10. ELIGIBILITY CRITERIA • Inclusion: identify participants that: • Have the potential to benefit from the intervention. • Have a high probability of developing the outcomes of interest. • Exclusion: identify subjects who satisfy inclusion criteria but who also have: • Higher risk of unwanted events (allergic reactions, pregnant women, children) • High risk of competitive outcomes or events • Risk of not complying with the study protocol • Characteristics that are confounders

11. STEPS IN THE DESIGN TO SPECIFY THE SAMPLE Question Target population Study plan Intended sample Accessible population Step 1: Specify the clinical and demographical characteristics for the question. Step 2: Specify the characteristics (time and place) of the accessible population Step 3: Select a representative sample that satisfies the characteristics. Sampling Specifying selection criteria

12. SPECIFYING INCLUSION AND EXCLUSION CRITERIA Example: Comparison of IV and oral antibiotics in children hospitalized due to severe pneumonia. Age 3m to 5 years. Acute respiratory infection with chest indrawing Seen at 9 centers in 8 countries. April 1999 to March 2001. Inclusion criteria: Characteristics that define a population relevant and efficient for the study Target population: - Demographical - Clinical Accessible population: - Geographical - Temporal

13. SPECIFYING INCLUSION AND EXCLUSION CRITERIA Example: The following children will be excluded of the comparison of IV and oral AB in hospitalized children with severe pneumonia: • Allergy to the antibiotics • Asthma and other severe infections. • Not living in the city • Previous use of antibiotics or chronic disease Exclusion criteria: characteristics that define subgroups of individuals that are not to enter the study because of: • higher risk of adverse events • Higher risk of competitive events • higher risk of low compliance • Presence of confounders

14. SPECIFYING INCLUSION AND EXCLUSION CRITERIA • Criteria should: • must be acceptable and clearly applicable (not ambiguous) • be a balance between ideal and practical • help to determine how the findings can be applied to other populations. • Exclusion criteria are not just the opposite of inclusion criteria.

15. OBJECTIVES • Defining population and sample • Describing the elements needed to defining the eligibility criteria of a RCT • Describing the effect of the eligibility criteria on the external validity of a trial • Describing strategies for an optimal recruitment of subjects

16. TYPES OF ACCESIBLE POPULATION FOR RESEARCH 1. Hospital based: • Easier /cheaper to recruit • Potential for reference bias 2. Community based: • Reduction of the bias • Sampling more expensive / difficult

17. SAMPLING STRATEGIES 1. All population (census) 2. Random sample 3. Non random sample

18. STUDY OF ALL THE POPULATION • Optimal method if feasible. • Usually not feasible due to: • Accessible population too large or disperse. • Population is disseminated in time. • Costs

19. RANDOM SAMPLING • Each population member has a defined probability (and usually the same) of being selected for the sample • Method that produces the most rigorous base for: • Ensuring that the sample is truly representative • Estimating measures of random error (confidence intervals)

20. NON RANDOM SAMPLING • It is more practical than random sampling in most clinical situations • Different strategies: • Consecutive sampling • Convenience sampling • Selection by the investigator

21. NON RANDOM SAMPLING • Consecutive sampling: • Selection of each subject that within a lapse meets the eligibility criteria • Inadequate if the period of sampling is short or if there is a secular behavior • Convenience sampling: • Selecting the subjects of the population which are easily accessible. • Higher risk of having non-representative samples • Sampling by investigator selection: • Similar to convenience sampling • Greater possibility of bias by the investigator

22. OBJECTIVES • Defining population and sample • Describing the elements needed to defining the eligibility criteria of a RCT • Describing the effect of the eligibility criteria on the external validity of a trial • Describing strategies for an optimal recruitment of subjects

23. RECRUITMENT OF PARTICIPANTS Objectives: • Recruiting enough subjects within the time frame • Recruiting a non biased sample: • No technical sampling errors • With a good response rate

24. VOLUNTEER BIAS Volunteers usually have better results than non participants in the study

25. STRATEGIES TO IMPROVE THE RECRUITMENT RATE • Maximize the advantages of participating in the study • Discussion with colleagues and other centers • Diminish uncomfortable situations (queuing, waiting times, costs) • Moderate incentives (transport fee) • Repeated or complementary strategies to maintain contact