THE STUDY POPULATION Basic Workshop on Randomized Controlled

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

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 Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

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. Practihc Basic Workshop - Population

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? Practihc Basic Workshop - Population

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

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 Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

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

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

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

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. Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

SAMPLING STRATEGIES 1. All population (census) 2. Random sample 3. Non random sample Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

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) Practihc Basic Workshop - Population

NON RANDOM SAMPLING • It is more practical than random sampling in most clinical situations • Different strategies: – Consecutive sampling – Convenience sampling – Selection by the investigator Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

VOLUNTEER BIAS Volunteers usually have better results than non participants in the study Practihc Basic Workshop - Population

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 Practihc Basic Workshop - Population

Practihc Basic Workshop - Population

Practihc Basic Workshop - Population