Non-randomised studies

Methodologies for a new era summer school

School of Applied Social Studies, University College Cork

22 June 2011

Dr Paul MontgomeryJennifer Burton

Why bother?

The data from a good study can be analysed in The data from a good study can be analysed in many ways, but no amount of clever analysis many ways, but no amount of clever analysis

can compensate for the problems with the can compensate for the problems with the design of a study.design of a study.

(Altman, 1991)(Altman, 1991)

Introduction

It is sometimes impossible or undesirable to influence events in a human sample You may not be able to control group allocation It may be unethical to expose or withhold an

intervention

An appreciation of the varieties of study designs available can reduce the need to reinvent the wheel and to rediscover the mistakes of others. It can also help to end the “scandal of research”’

(Altman, 1993)

Aims

Identify types of questions that can be answered using non-randomised methods

Describe several non-randomised designsHighlight the strengths and weaknesses of

common non-randomised designs

Question to design

Prevalence/ incidenceRisk and protective factorsPrognosisHarmEffectiveness

Internally Valid

Evidence of Effectiveness

Meta-Analysis of Randomised Trials Randomised Trials

Non-randomised studies Cohort studies Case-Control studies

Non-comparative studies Case Series (open trial)

Case reports

Expert opinion

The Hierarchy of EvidenceFor Intervention Studies

Illustrative examples, hypothesis generating studies

Question to Design

In practice, methods tend to be complementary in answering questions

Each method may be used to answer several types of questions

Several studies may help tease apart a question

Prevalence

How many people have mental health disorders?

Surveys

Census (one-time full population) Ideal but expensive, difficult, likely to miss people

from marginal groups

Cross section (one-time sample) Must consider many potential biases due to

geography, time, etc.

Cross-Sectional Survey

Identify a sample of adults representative of the population

Measure symptoms of mental health problems

Calculate the number of people above a given threshold

Surveys

Usefully estimate prevalence or incidence and associations

Comparisons may be made between different subgroups to identify associations

Risk and Protection

Does smoking cause cancer?

Risk and Protection

What factors can predict falls in the elderly?

Retrospective Cohort

Take all elderly people in OxfordLook at

Characteristics of their homes Individual factors (e.g. medication

use) Other predictors?

Look for association between these factors and falls

Retrospective Cohort

Backward looking surveyRelatively inexpensive and practicalGood for detecting latent outcomesProne to several sources of bias (selection,

participant recall, etc.)

Risk and Protection

What are the factors that contribute to chronic fatigue syndrome?

Prospective Cohort

Take all babies born in a given period in 1970

Survey them regularlyLook for correlations between

variables (e.g. maternal depression) and outcomes (e.g. chronic fatigue)

Prospective Cohort

Identifies temporal relationshipsCan examine multiple effects of exposure Loss-to-follow-up can be a problem Inefficient for the evaluation of rare problems

unless the attributable risk is high e.g. 1970 British Cohort Study (ongoing)

http://www.cls.ioe.ac.uk/

Risk and Protection

Is fish oil good for my mental health?

Ecological Studies

Compare countries’ consumption of fish oil to their rates of depression

Increased consumption of fish oil lowers a nation’s rate of depression (Hibbeln 2001), but eating fish is not the only difference among countries

Ecological Studies

Large unit of analysis (e.g. countries)May identify population-level risk and protective

factorsBecause the unit of observation is not the

individual subject, they are subject to the ecological fallacy when they overlook important sources of variance

Risk and Protection

Is running bad for my knees?

Case Control

Identify a group of runnersThen find a group of people who

don’t run matched for age, sex, weight and other variables

Test for associations between knee problems and being a runner

Case Control

Inexpensive and practicalGood for generating hypothesesLacks a temporal dimensionUnless data come from a population-based

survey, cannot give incidence and prevalence data

Prognosis

My husband has just taken 4 times the recommended dose of purple pills.

What’s going to happen?

Case Report

An otherwise healthy 60 year old man was prescribed 10 mg of vardenafil (Levitra, Bayer) for sexual dysfunction. Because this was ineffective, he increased the dose to 40 mg. Three hours later, he had a tonic-clonic seizure, seen by his relatives.

On admission to hospital, neurological examination, brain magnetic resonance imaging, and electroencephalography after sleep deprivation were normal. Stress electrocardiography, echocardiography, and cardiac scan with dipyridamole test as well as carotid doppler ultrasonography did not show concomitant cardiac diseases. The man was told to stop using vardenafil.

Two months later he had a new tonic-clonic seizure, four hours after taking 30 mg of vardenafil. At eight months' follow-up he is seizure-free without treatment.

Pasquale Striano, Federico Zara, Carlo Minetti (professor of paediatrics), Salvatore Striano (2006). Epileptic seizures can follow high doses of oral vardenafil. BMJ;333:785.

Case Report

Inexpensive and quickMay draw attention to important

clinical and research issuesIn rich detail, describes conditions

and outcomes May not be representative, does

not usually provide evidence of causation

Case Series

Several case studiesDraws attention to patterns in client populationsCommon in aetiological research

Break

Effectiveness

Does abstinence education reduce the likelihood of premarital sex?

Pre-post (single group)

Take a class of kidsAsk them if they will have sex before marriageThey attend an abstinence-based education

programmeAsk them if they will have sex before marriage

Pre-post (single group)

Inexpensive, generally easier than controlled studies

Provides some evidence of temporal relationships

Usually lacks a plausible counterfactual (i.e. what would have happened in the absence of intervention)

Effectiveness

Does Head Start improve IQ?

Between Group

Look at all the kids in New York born in 1980 who were eligible for Head Start

Compare those who attended to those who did not attend

If possible, collect measures before and after attendance

Between Group

Provides a counterfactual scenario, can give evidence of temporal relationships.

Groups may differ on both measured and unmeasured variables, observed differences may be attributable to factors other than the intervention.

Effectiveness

Does having regular contact with a social worker improve outcomes for fostered children?

Historical Control

Compare children in foster care since the 1944 education act to children in foster care before then.

If possible, include measures before and after enrolment for children in each group.

Historical Control

Provides a counterfactual scenarioGroups may differ on both

measured and unmeasured variables, observed differences may be attributable to factors other than the intervention

Effectiveness

Do intensivepolice

crackdowns reduce gun

violence?

Time-Series

Identify areas with high levels of gun crime and identify peak times

Repeatedly use crackdowns during periods of high crime

Compare times with the intervention to periods without the intervention

Time-Series

Provides a counterfactual scenarioTimes may be different Often requires complicated

statistical analyses to control for differences in baseline variables, time trends, etc.

Conclusion

What is your question?What types of study design might

contribute to an answer?Think ‘Horses for Courses’