New statistics for the self-controlled case series method: weakening the assumptions

Lead Research Organisation: Open University
Department Name: Mathematics & Statistics


An important statistical problem in many fields is to determine whether one variable, called the exposure, affects the occurrence of an event of interest. For example, does administering a drug cause adverse reactions; do certain production modes increase the chance of faults in a manufacturing process; does the occurrence of one life event affect the likelihood of another. Various statistical methods have been developed to identify associations such as these, and to estimate their strength. This project is concerned with one particular method, the case series method, which has emerged relatively recently.This method differs from others in that only individuals (or items) that have experienced the event of interest need to be sampled. Thus, individuals who have not experienced the event are not needed. This is advantageous when the event of interest is rare. Comparisons are made within each individual's period of observation, with the additional benefit that many of the factors that might distort the association between the exposure and the event, known as confounding factors, are automatically allowed for. This double benefit - reduced study size and good control of confounding factors - comes at a price, namely the need for stronger assumptions than are required by other methods. The purpose of the present project is to study these assumptions, in order better to understand their role, if possible weaken them, and hence widen the range of application of the method.The project is important because the case series method is increasingly being used in a range of fields, particularly in epidemiology. This is because it is relatively cheap, and makes possible studies which otherwise would be impractical or biased (for example, in epidemiology, if the patients most likely to suffer the event also tend to be those that experience the exposure). However, as the method grows in popularity, the temptation to apply it without due regard to the assumptions increases. Relatively little work has been done to check whether the assumptions are really needed, and whether they may be weakened in various ways. We will look at four key assumptions. The first, and probably most restrictive requirement, is that exposures are unaffected by previous events. This assumption fails if, for example, the event of interest is death. Our main objective under this heading will be to develop a case series method that works for events such as deaths.The second key assumption relates to point exposures, that is, exposures that occur at a particular point in time, like a vaccination, or a power surge. For such exposures, a risk function is defined which describes how the chance of occurrence of the outcome event varies after the point exposure. At present, some assumptions are required about the shape of the risk function, and in particular the duration of the increased risk period. We will study more flexible risk functions, which do not require such assumptions.The third assumption we will investigate is that, if an individual experiences several events, then these occur independently of each other. This is often not true in practice: for example, occurrence of one failure in a piece of machinery might increase the chance of subsequent failures. We will develop a test of independence of recurrent events, valid for case series analyses.Finally, the fourth assumption we will study is that the period of observation does not depend on the timing of events. This is not the case when, for example, the event increases the chance of death, as with heart attacks. We will study the extent to which failure of this assumption affects the results.This project will produce new statistical theory for the case series method, leading to better understanding and hence wider use of the method. The findings will be published in peer-reviewed journals and on the case series website at


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Farrington C (2010) Within-individual dependence in self-controlled case series models for recurrent events in Journal of the Royal Statistical Society: Series C (Applied Statistics)

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Farrington C (2011) Self-Controlled Case Series Analysis With Event-Dependent Observation Periods in Journal of the American Statistical Association

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Farrington CP (2009) Case series analysis for censored, perturbed, or curtailed post-event exposures. in Biostatistics (Oxford, England)

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Hocine M (2009) Sequential case series analysis for pharmacovigilance in Journal of the Royal Statistical Society: Series A (Statistics in Society)

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Whitaker HJ (2009) The methodology of self-controlled case series studies. in Statistical methods in medical research

Description We extended the self-controlled case series (SCCS) method to apply in situations where poccurrence of an event can alter subsequent exposures, and when events carry an increase in the risk of short-term mortality, which influences the observation period. We also investigated other extensions to the SCCS method, notably to dependent recurrent events.
Exploitation Route These extensions of the SCCS method have already been taken up my medical researchers interested in the possible adverse events associated with pharmaceutical drugs, including vaccines.
Sectors Healthcare

Description The research from this project has had a profound impact on the versatility of the self-controlled case series method, resulting in a substantial increase in its use, notably in non-vaccine pharmacoepidemiology, but also in new vaccine applications related, for example, to seasonal and pandemic influenza vaccines.
First Year Of Impact 2010
Sector Healthcare
Impact Types Economic

Title Self-controlled case series method for event-dependent observation periods 
Description Extends the SCCS method to situations where the observation period is event-dependent, as occurs when events increase mortality 
Type Of Material Data analysis technique 
Year Produced 2011 
Provided To Others? Yes  
Impact Has been applied to the analysis of stroke and myocardial infarction 
Title Self-controlled case series method for exposure-modifying events 
Description Extends the SCCS method to situations in which the event alters the subsequent probability of exposure 
Type Of Material Data analysis technique 
Year Produced 2008 
Provided To Others? Yes  
Impact This extension has widely been used, for example to investigate the impact of influenza vaccine on Guillain Barre syndrome 
Description PHE - SCCS 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution Method development
Collaborator Contribution Provision of data, epidemiological advice
Impact Joint papers, conference presentations
Start Year 2007
Description University of London - SCCS 
Organisation University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Method development
Collaborator Contribution Provision of data
Impact Joint publications, conference presentations
Start Year 2007