Study design

Pharmacoepidemiological study design

1. Study Design Department of Clinical Pharmacy Ashish Singh Parihar

2. Are you going to observe or experiment? O bservational – cross sectional, case series, case-control studies, cohort studies identify participants observe and record characteristics look for associations E xperimental – before and after studies, comparative trials (controlled or head to head), randomised trials (ditto) identify participants place in common context intervene observe/evaluate effects of intervention

3. Study Designs Case Reports Case Series Analyses of Secular Trends Case – Control Studies Cohort Studies Randomized Clinical Trials

4. Did the investigator manipulate / intervene? Yes No Experimental study Observational study Random allocation Yes No RCT Non RCT Analytical Descriptive Case control Cohort Algorithm for Classification of Study Designs Cross sectional study / Longitudinal study

5. ANALYTICAL STUDIES ECOLOGICAL – CORRELATIONAL CROSS SECTIONAL – PREVALENCE CASE CONTROL- CASE REFERENCE COHORT – FOLLOW UP

6. Case Reports Are simply reports of events observed in single patients. Useful for raising hypotheses about drug effects. Leads to the drug test with more rigorous study design. Very rare to use to make a statement of causation. Exception to this is when the outcome is very rare and so characteristic that one knows that it is due to the exposure. Is accepted when challenge situation is very fatal.

7. Case Series Collections of patients, all of whom have a single exposure, whose clinical outcomes are then evaluated and described. Alternatively case series can be collection of patients with a single outcome, looking at their antecedent exposure. Useful for quantifying the incidence of an adverse reaction or whether occurs in larger population. Just provides clinical descriptions of a disease or of patients who receive an exposure.

8. Case – Control Studies Compare cases with the disease to controls without the disease, looking for differences in exposure. Multiple possible causes of a single disease can be studied. Helps in studying relatively rare disease requires smaller sample size. Information are generally obtained retrospectively from the medical records, by interviews or questionnaires. Limitations are validity of retrospective information and selection of control is challenging task. Inappropriate control selection can lead to incorrect conclusion.

9. Pros and cons of case-control study Patients with a certain outcome or disease and an appropriate group of controls, without the outcome or disease, are selected (usually with some matching) then information is obtained on whether the subjects have been exposed to the factor under investigation. Advantages: quick and cheap as fewer people needed than cross-sectional studies only feasible method for very rare disorders or those with long lag between exposure and outcome Disadvantages: reliance on recall or records to determine exposure status confounders selection of control groups is difficult potential bias: recall, selection

10. Cohort Studies Identify subsets of a defined population and followed them over time, looking for differences in their outcome. Used to compare exposed patients to unexposed patients, can also be used to compare one exposure to another or when multiple outcomes from single exposure is to be studied. Either done prospectively or retrospectively. More reliable causal association. But requires large sample size (even for an uncommon outcome) and can require prolonged time period to study delayed outcomes.

11. Pros and cons of cohort study Data obtained from groups who have already been exposed, or not exposed, to the factor of interest. No allocation of exposure is made by the researcher. Best for studying effects of risk factors on an outcome. Advantages: ethically safe participants can be matched can establish timing and directionality of events eligibility criteria and outcome assessments can be standardised Disadvantages: controls may be difficult to identify exposure may be linked to a hidden confounder blinding is difficult for rare disease, large sample sizes or long follow-up necessary

12. Cross sectional study

13. Pros and cons of cross sectional study Examines the relationship between 1) diseases/other health related characteristics and 2) other variables of interest as they exist in a defined population at one time. Exposure and outcomes both measured at the same time. Quantifies prevalence, risk, or diagnostic test accuracy Advantages: cheap and simple ethically safe Disadvantages: establishes association at most, not causality recall bias, social desirability bias researcher’s (Nyman) bias group sizes may be unequal confounders may be unequally distributed

14. Randomized Clinical Trials An experimental study – the investigator controls the therapy that is to be received by each participant. Major strength is the randomization. Problems might include the ethical issues and are expensive. They are not of big importance after marketing.

15. Pros and cons of the RCT An experimental comparison study where participants are allocated to treatment/intervention or control/placebo groups using a random mechanism. Best for studying the effect of an intervention. Advantages: unbiased distribution of confounders blinding more likely randomisation facilitates statistical analysis Disadvantages: expensive: time and money volunteer bias ethically problematic at times

16. Pros and cons of crossover trial A controlled trial where each participant has both therapies e.g is randomised to treatment A first then starts treatment B. Advantages: all participants serve as own controls and error variance is reduced, thus reducing sample size needed all participants receive treatment (at least some of the time) statistical tests assuming randomisation can be used blinding can be maintained Disadvantages: all participants receive placebo or alternative treatment at some point washout period lengthy or unknown cannot be used for treatments with permanent effects

17. Quasi-Experimental Design A structured, organized method To determine whether some program or treatment causes some outcome or outcomes to occur. If X, then Y Because there may be lots of reasons, other than the program, for why you observed the outcome, If not X, then not Y needs to be addressed, too

18. To show that there is a casual relationship, Two “equivalent” groups The program or treatment group gets the program The comparison or control group does not The groups are treated the same in all other respects Differences in outcomes between two groups must be due to “the program”