PHAR INFO LEC - 3.2 Research Designs and Methods

Study Design

• Overall plan that allows researchers to seek answers to study questions and test study hypotheses

• Like a blueprint or roadmap on what kind of research would be conducted

Primary Studies

Studies performed firsthand by the researchers

• Basic medical studies

• Clinical studies

• Pharmacoepidemiologic studies

• Pharmacoeconomic studies

Basic Medical Studies

• Many of these are pre-clinical studies

• Experimental in nature

  • Animal studies

  • Cell studies

  • Biochemical genetic, physiologic studies

  • In-vitro drug studies, formulation studies

Clinical Studies

Conducted on humans to evaluate a number of outcomes

• Etiology or mechanism of disease

• Diagnosis

• Prevention

• Interventions of disease management

• Safety

Pharmacoepidemiologic Studies

Study of potential impact of drug therapy or clinical services in large numbers of patients using principles of epidemiology

Pharmacoeconomic Studies

Studies that describe and analyze the costs and consequences of drug therapy

• Cost-minimization analysis

• Cost-effectiveness analysis

• Cost-benefit analysis

• Cost-utility analysis

Descriptive Studies

• Describe/summarize information about a population or phenomenon without making any casual inferences

• Answer “Who,” “What,” “Where,” and “When,” but does not answer “Why” and “How” characteristics have occurred

• Mostly used to generate hypothesis

Analytical Studies

• Aim to understand the relationship and/or casual mechanism that may exist between 2 or more variables

• Try to answer “Why” and “How”

• Test hypotheses; quantify the relationship between an intervention and an outcome

  • Inferential statistics (ex. T-test, ANOVA)

Prospective Studies

• Also called longitudinal studies

• Researcher collects data after study onset by following individuals over a period of time

• More resource intensive

Retrospective Studies

• Evaluation of data from past events/existing data

• Researcher cannot control past events/data collection methods

Interventional

• Researcher controls the treatment

• Relies on primary data

• Typically seen when you want to see intervention and an outcome

Observational

• Researcher observes the relationship between study variables in a natural setting (real world)

• Uses primary data (surveys, interviews), or secondary data (medical charts)

Descriptive

Descriptive or Analytical?

Prevalence of HTN in Tondo, Manila

Analytical

Descriptive or Analytical?
Relation between smoking and lung cancer

Descriptive

Descriptive or Analytical?

Women satisfaction for antenatal care

Analytical

Descriptive or Analytical?

Effect of gestational obesity on fetal outcome

Analytical

Descriptive or Analytical?

Risk of lead exposure on mental retardation

Descriptive

Descriptive or Analytical?

Suggestions for improvement of UMC

Cross-sectional Study

• Researcher collects data at one point in time/short period of time

• Advantages:

  • Less time-consuming and less expensive

  • No problem of dropouts

• Limitation:

  • Not practical for rare diseases

Purpose/Application of Cross-sectional Study

Purpose/Application:

• Measure prevalence of risk or disease

• Describe variable/s with no attempt to find a relationship between them

Case Report

• Detailed analysis of a person/group with a particular disease or condition

• Advantages:

  • May be the only realistic design for rare disorders

• Limitation:

  • Biased reporting: Negative findings not published

Case Series

• Group of case reports involving patients with common characteristics

• Advantages:

  • May be the only realistic design for rare disorders

• Limitation:

  • Biased reporting: Negative findings not published

Surveillance Study

• Collection, analysis, and interpretation of health data

• For:

  • infections

  • ADR/ADE

Purpose/Application of Surveillance Study

Purpose/Application:

• Act as early warning system for disease outbreaks or for planning long-term strategies

Ecological Study

• Unit of observation is a group or population, rather than an individual

• Look for possible associations between exposure and outcomes in populations

• Limitation:

  • High susceptibility to confounding (bias)

Purpose/Application of Ecological Study

Purpose/Application:

• Highlight possible correlations between an exposure and an outcome in a population

Observational

• Looks for the possible relationship of exposure and outcome

• Researcher has no control

Analytical Cross-Sectional Study

• Examines the relationship between exposure and outcome as they exist in the population at one time

• Exposure and outcomes are both measured at the same time

• Advantages:

  • Less time-consuming and less expensive

  • No problem of dropouts

  • Few ethical hurdles

• Limitation:

  • Establishes association at most, not causality

  • Subject to bias and confounding

  • Not practical for rare diseases

Purpose/Application of Analytical Cross-Sectional Study

Purpose/Application:

• Best for quantifying the prevalence of a disease or risk factor, and for quantifying the accuracy of a diagnostic test

Cohort Study

• Longitudinal study that compares the outcome of an exposed group with an unexposed group

• Track people forward in time from exposure to outcome

• Advantages:

  • Can establish the temporal sequence between exposure and outcome

  • Few ethical hurdles

• Limitation:

  • Time-consuming and expensive

  • Not suitable for rare diseases

  • Selection bias and change in exposure status can affect outcomes

  • Loss to follow-up can be a problem

• Recruitment of participants is always based on exposure; they do not have the outcome yet

• Can encounter both prospective (most) and retrospective

Purpose/Application of Cohort Study

Purpose/Application:

• Most scientific way to find out the incidence and natural history of any disorder

• Investigation of multiple outcomes after a single exposure

• Studying outcomes of rare exposures

• Reduce the risk of survivor bias

Cohort

Group of people with common characteristics and are followed over time from an exposure to one or more outcomes

Case-Control Study

• Patients with a certain outcome or disease (cases) and an appropriate group of controls without the outcome or disease are selected

• Compares the exposure of the cases with the controls

• Both groups are followed backward in time to measure past exposure

• Advantages:

  • Less time-consuming and cheaper

• Limitation:

  • Population and time period from which cases arose are not known

  • Can only study one outcome at a time

  • Prone to selection bias and measurement bias

• Opposite of Cohort Study

• Recruitment is based on outcomes

• Always on retrospective

Purpose/Application of Case-Control Study

Purpose/Application:

• Most efficient study design for finding possible associations between exposures and outcomes

• For rare diseases

• For diseases with a very long latent period between exposure and outcome

Example of Case Study

Example of?

Example of Cross-Sectional Study

Example of?

Example of Cohort Study

Example of?

Basic Medical Study

• Include animal experiments, cell studies, biochemical, genetic, and physiologic investigations

• Include studies of properties of drugs and materials

• Purpose/Application:

  • Pre-clinical studies which provide the basis for clinical trials

  • Bioequivalence studies of generic products

Epidemiologic Trial

Involve populations in community (real-world) settings

a. Field trials – intervention is given to individuals who are healthy but at risk; purpose is to test a preventive intervention

b. Community trial – intervention is applied to communities rather than individuals

Purpose/Application:

• Determine real-world effectiveness of interventions

• Testing preventive and educational strategies

Field Trials

Intervention is given to individuals who are healthy but at risk; purpose is to test a preventive intervention

Community Trial

Intervention is applied to communities rather than individuals

Clinical Trial

Studies involving humans which follow a predefined plan or protocol to determine the safety and effectiveness of medical products and practices

• Advantages:

  • Minimizes bias and confounding (especially if RCTs)

• Limitation:

  • Generally expensive and time-consuming

  • Addresses narrow clinical questions

  • Often expose participants to potential harm

• Purpose/Application:

  • Lead to the development of new drugs, therapies, and interventions

Randomized Controlled Trials

• Gold standard of research designs and the foundation for evidence-based medicine

• Experimental comparison study in which participants are allocated to intervention (treatment) or control groups using randomization

• All participants have an equal chance of being allocated to an intervention or control group, eliminating selection bias

• Must be conducted according to principles and standards of good clinical practice (GCP)

Type of Study: Non-Randomized Clinical Trial

What type of study?

• Patients with asthma were assigned alternatively (every other patient) to receive Drug A pr standard therapy.

• Neither patients nor doctors were blinded.

Type of Study: Cohort Study

What type of study?

• Researchers compared outcomes of patients who chose to take herbal supplements vs those who did not by following-up with patients over a 2-year period.

Type of Study: Clinical Study (Interventional)

What type of study?

• Participants received Drug A for 4 weeks, then after a washout period, received placebo.

• Outcomes were compared within the same individuals.

Type of Study: Cross-Sectional Study

What type of study?

• A study was conducted to examine the relationship between daily sodium intake and blood pressure levels.

• Participants completed a dietary survey and had their blood pressure measured during a single clinic visit.

Randomization

• Process of assigning patients to a treatment or control group by chance alone

• Highly effective in reducing biases and confounding in a study

Simple Randomization

Randomization:

• Random number generator

• Simple but can lead to unequal number of subjects in groups (studies with small sample size)

Block Randomization

Randomization:

• Ensures treatment groups have equal numbers

• Total number of subjects is divided into a series of ”blocks”

Stratified Randomization

Randomization:

• Ensures that baseline characteristics are equal between groups

Group or Cluster Randomization

Randomization:

• Groups of subjects are selected for randomization

• All members of the cluster receive the same treatment

Allocation Concealment

• Those enrolling patients into the study are prevented from knowing which group the patients are allocated to

• Prevents selection bias

• Occurs prior to the patients being enrolled in the study and stops once they are enrolled

  • Happens before enrollment

Blinding/Masking

• Those involved in the trial are unaware of what treatment the patients are receiving

• Patients, investigators (inc. data analyzers), data collectors/ care providers

• Starts as soon as patients are enrolled in the study

  • Happens after enrollment

Open Label

• everyone knows the treatment

• prone to bias

Single Blind

• done only if outcome measurements are purely objectives

• healthcare provider and data analyst know

Double Blind

• participant and healthcare provider do not know

Triple Blind

• everyone do not know

Placebo Concurrent Control

• In cases where there is no known effective therapy

• Identical in appearance to the intervention; containing an inert substance

Active Control

• In cases where there is a known or accepted standard of care

• For disease states where it is not ethical or possible to administer a placebo to patients requiring treatment

• Should be an equivalent dosing

Historical (External) Control

• External group of patients that were observed at a different time or in a different treatment setting

• Advantage is that all participants in the study receives the intervention

• Disadvantage: participants and investigators are unblinded

Parallel Design

• Each subject is randomized to either a treatment group or control group

• All members of the group receive the treatment/ placebo over the duration of the study

Crossover Design

• Each subject receives all of the interventions based on a specified sequence of events

  • After some time, there will be a switch to the other treatment group after washout period

• Reserved for diseases that are stable and consistent over time

Factorial Design

• Evaluate multiple interventions in a single experiment (e.g., multiple doses, drug regimens)

Adaptive Design

• Assigning patients to a treatment group based on the previous success of the treatment as the trial progresses

Drug efficacy Study

• Determines the effects of an intervention under tightly controlled conditions

• Most RCTs conducted during drug development

• Have very narrow inclusion and exclusion criteria

Drug Effectiveness Study

• Determines the effects of an intervention under conditions that the drug is most often used in the clinical setting (real-world)

• Clinical trials conducted during the post-marketing phase