Case Series Method Research Articles

Assessment of the “Case-Chaos” Design as an Adjunct to the Case-Control Design

In 2012, a novel case series method dubbed the "case-chaos" design was proposed as an alternative to case-control studies, whereby controls are artificially created by permutating the exposure information of the cases. Our aim in the current work was to further evaluate the case-chaos method. Using a theoretical example of 2 risk factors, we demonstrated that the case-chaos design yields risk estimations for which the odds ratios obtained for every risk factor are in the same ascending order as the risk factors' exposure prevalences in the case group. Applying the method to data from the European Study of Severe Cutaneous Adverse Reactions (EuroSCAR; 1997-2001), we were not able to obtain sensible results but instead produced results as predicted by our theoretical assessment. We therefore claim that the method is equivalent to declaring risk solely on the basis of prevalences obtained in cases. While the proposers of the case-chaos method view it as a useful adjunct, we show that it cannot produce sensible estimates.

Clinical Evaluation of 188 Patients with Contracted Socket

Purpose: To evaluate our results in the management of socket contraction. Design: Case series Method: One hundred and eighty eight patients with contracted sockets were retrospectively analyzed. Reasons for eye removal, type of initial surgery, presence of an implant, time of onset of contraction, degree of contraction, additional pathologies accompanying contraction, type of surgery for the contracted socket, additional interventions, number of surgeries, and final status were recorded and evaluated. Results: There were 101 (53.72%) male and 87 (46.28%) female patients, with an age range between 1 and 78 years (mean 35.46 years). Mean follow-up was 45.6 ± 22.34 months (range 5-120 months). Trauma was the reason for eye removal in 80(42.55%) patients. Enucleation performed in 146(77.66%) patients was the most common initial surgery. An implant was absent in 143(76.06 %) patients. Time of onset of contraction was longer than 5 years in 56 (29.79%) patients. Moderate or severe contraction was recorded in 134(71.28%) patients. Totally 229 procedures were performed for socket surface expansion and 30.32% of patients required more than one surgery. 151(80.32%) patients had additional pathologies. At the final visit, 138 (73.4%) patients had a good or acceptable result. Conclusion: Contracted socket remains to be a challenging entity of oculoplastic surgery. It may develop at any time following removal of the eye. Additional pathologies frequently accompany the contracted socket. Even though wearing an artificial eye eventually becomes possible in the majority of cases, it is still hard for some patients even after a series of reconstructive interventions.

Intraosseousenign Lesions of the Jaws: A Radiographic Study

Background:Benign maxillo-mandibular tumors and cysts, which are relatively common findings on radiographs, namely the ubiquitous panoramic view, have to be dealt with by dentists on a daily basis.Objectives:The aim of this study is to evaluate the panoramic radiographic findings pertaining to benign and tumoral lesions in the maxilla and mandible.Patients and Methods:Applying a case series method, panoramic images of 61 patients with cysts, benign tumors and tumor-like lesions in the jaws who were referred to Hamedan dental school between 2009 and 2011 were evaluated by two radiologists. They were both blind to histopathological results as well as the objectives of our study. Lesions were assessed based on their location, periphery, internal structure and impaction on the surrounding structures. Then the obtained data were analyzed using descriptive tables.Results:Cysts were mostly more common in men despite the equal propensity of both genders to benign tumors. In contrast, women showed a higher frequency of tumor-like lesions. The most common site of involvement was the posterior mandible, with peri-apical tooth lesions as the most prevalent dental association. Radiographically, what we most encountered was unilocular radiolucency pertaining to cysts and benign tumors; nevertheless, tumor-like lesions tended to present with a well-defined radiopacity.Conclusions:Despite its known shortcomings, like every other diagnostic tool, panoramic radiography can contribute to the early detection of maxillary/mandibular lesions that in turn enable the dentist to devise an appropriate treatment plan.

Proton Pump Inhibitors and the Risk of Adverse Cardiac Events

BackgroundRecent evidence suggests that proton pump inhibitors (PPIs) might be linked with adverse cardiac events, but a causal relationship is unproven.MethodsWe applied the self-matched case series method to two studies using population-based health care data from Ontario, Canada between 1996 and 2008. The first included subjects aged 66 years or older hospitalized for acute myocardial infarction within 12 weeks following initiation of PPI, while the second included subjects hospitalized for heart failure. In both studies we designated the primary risk interval as the initial 4 weeks of therapy and the control interval as the final 4 weeks. To test the specificity of our findings we examined use of histamine H2 receptor antagonists and benzodiazepines, drugs with no plausible causal link to adverse cardiac events. ResultsDuring the 13-year study period, we identified 5550 hospital admissions for acute myocardial infarction and 6003 admissions for heart failure within 12 weeks of commencing PPI therapy. In the main analyses, we found that initiation of a PPI was associated with a higher risk of acute myocardial infarction (odds ratio 1.8; 95% confidence interval 1.7 to 1.9) and heart failure (odds ratio 1.8; 95% confidence interval 1.7 to 1.9). However, secondary analyses revealed similar risk estimates histamine H2 receptor antagonists and benzodiazepines, drugs with no known or suspected association with adverse cardiac events.ConclusionPPIs are associated with a short-term risk of adverse cardiac events, but similar associations are seen with other drugs exhibiting no known cardiac toxicity. Collectively these observations suggest that the association between PPIs and adverse cardiac events does not represent reflect cause-and-effect.

The association between multidose vaccinations and death: comparing case series methods when the first exposure changes the general risk of an event

Many case-control studies have shown a protective effect of vaccinations on the risk of sudden unexplained death (SUD). In this paper we compare the properties of different statistical methods in this situation, when the first vaccination appears to reduce the overall risk of an event (SUD). The first method is the self controlled case series (SCCS) method, which considers only subjects with an event during the observation time. This method yields unbiased estimates in the situation of non-censoring events. We show by simulation studies that the second method considered, the adjusted SCCS method, underestimates the parameter of interest, the effect of the first dose, when the general risk of SUD is lower in control periods after the first vaccination than in the period before vaccination. This type of bias could be eliminated by considering only cases who had received at least one vaccination. Additionally, we compare the adjusted SCCS method with the Cox model as a third method. Cox regression can take into account the time before the first vaccination, and this method yields unbiased estimates at modest effect sizes and short risk periods. We applied the SCCS method and Cox regression to data from the German study on sudden infant death (GeSID) and to a case series study from Italy (the HERA study) examining sudden unexpected deaths and vaccinations during the first 2 years of life. We show that the adjusted SCCS analysis with all cases underestimates the vaccination effect, as expected from the simulation analyses. Using Cox regression, we examined the general risk reduction after vaccination, as was the focus of the above mentioned studies. With a relative incidence of 0.8, our results were less pronounced than in the case-control analysis of the GeSID study (adjusted odds ratio: 0.51). SCCS analyses of both the GeSID and HERA studies yielded very similar estimates for the first and second vaccine doses.

Bias Correction of Risk Estimates in Vaccine Safety Studies With Rare Adverse Events Using a Self-controlled Case Series Design

The self-controlled case series (SCCS) method is often used to examine the temporal association between vaccination and adverse events using only data from patients who experienced such events. Conditional Poisson regression models are used to estimate incidence rate ratios, and these models perform well with large or medium-sized case samples. However, in some vaccine safety studies, the adverse events studied are rare and the maximum likelihood estimates may be biased. Several bias correction methods have been examined in case-control studies using conditional logistic regression, but none of these methods have been evaluated in studies using the SCCS design. In this study, we used simulations to evaluate 2 bias correction approaches-the Firth penalized maximum likelihood method and Cordeiro and McCullagh's bias reduction after maximum likelihood estimation-with small sample sizes in studies using the SCCS design. The simulations showed that the bias under the SCCS design with a small number of cases can be large and is also sensitive to a short risk period. The Firth correction method provides finite and less biased estimates than the maximum likelihood method and Cordeiro and McCullagh's method. However, limitations still exist when the risk period in the SCCS design is short relative to the entire observation period.

A New Self-Controlled Case Series Method for Analyzing Spontaneous Reports of Adverse Events After Vaccination

In this paper, we propose new methods for analyzing cases of vaccine adverse events spontaneously reported to a surveillance database. The methods use the self-controlled case series approach, extended in several ways with parametric and nonparametric assumptions to account for the specific features of the data (large amount of underreporting and variation of reporting with time since vaccination). This work was motivated by the documented risk of intussusception after RotaShield vaccination (Wyeth-Lederle Vaccines, Radnor, Pennsylvania) and used worldwide spontaneous reports of intussusception occurring after Rotarix vaccination (GlaxoSmithKline Biologics, Research Triangle Park, North Carolina) collected between January 2004 and February 2010. The estimated risk during the 3- to 7-day period after vaccination was approximately 5 times higher after dose 1 of Rotarix than after dose 2, which is similar to published findings on the same topic. We undertook a large simulation study to evaluate the performance of the method in different scenarios, including its robustness to different sample sizes and time-dependent reporting functions. The bias was generally small, the type I error rate was correctly controlled, and the power to detect a risk ratio of 4 was satisfactory, provided that the sample size was over 100. The proposed methods are an effective way to explore and quantify vaccine safety signals from spontaneous reports.

Self‐controlled case series method with smooth age effect

The self-controlled case series method, commonly used to investigate potential associations between vaccines and adverse events, requires information on cases only and automatically controls all age-independent multiplicative confounders while allowing for an age-dependent baseline incidence. In the parametric version of the method, we modelled the age-specific relative incidence by using a piecewise constant function, whereas in the semiparametric version, we left it unspecified. However, mis-specification of age groups in the parametric version can lead to biassed estimates of exposure effect, and the semiparametric approach runs into computational problems when the number of cases in the study is moderately large. We, thus, propose to use a penalized likelihood approach where the age effect is modelled using splines. We use a linear combination of cubic M-splines to approximate the age-specific relative incidence and integrated splines for the cumulative relative incidence. We conducted a simulation study to evaluate the performance of the new approach and its efficiency relative to the parametric and semiparametric approaches. Results show that the new approach performs equivalently to the existing methods when the sample size is small and works well for large data sets. We applied the new spline-based approach to data on febrile convulsions and paediatric vaccines. Co

Self-controlled case-series (SCCS) method as a tool for the evaluation on the safety of vaccine

Safety on vaccine issues has been under greater concern. Epidemiologically, classical study designs on investigating the association between a rare adverse event and vaccine inoculation usually confronted with lower feasibility in practice. Self-controlled case series (SCCS) method was derived from cohort studies. The key advantage of this method is that it only uses data related to cases and trying to find relative incidence of events in the 'at risk' periods relative to the 'controlled' periods. A further benefit of this method is that all the fixed confounders are controlled implicitly, by self-control, thus provides high statistic powers. With these advantages, SCCS is suitable for the causality assessment on rare but severe adverse events caused by immunization, which has been widely used,abroad. However,the methodology of SCCS is still being developed,and the areas in use have been expanded to the studies related to the safety and effectiveness of drugs, efficacy of vaccines as well as risk factors of disease.

Fractional polynomial adjustment for time‐varying covariates in a self‐controlled case series analysis

The self-controlled case series method is a statistical approach to investigating associations between acute outcomes and transient exposures. The method uses cases only and compares time at risk after the transient exposure with time at risk outside the exposure period within an individual, using conditional Poisson regression. The risk of outcome and exposure often varies over time, for example, with age, and it is important to allow for such time dependence within the analysis. The standard approach for modelling time-varying covariates is to split observation periods into blocks according to categories of the covariate and then to model the relationship using indicators for each category. However, this can be inefficient and can lead to problems with collinearity if the exposure occurs at approximately the same time in all individuals. As an alternative, we propose using fractional polynomials to model the relationship between the time-varying covariate and incidence of the outcome. We present the results from an analysis exploring the association between rotavirus vaccination and intussusception risk as well as a simulation study. We conclude that fractional polynomials provide a useful approach to adjusting for time-varying covariates but that it is important to explore the sensitivity of the results to the number of categories and the method of adjustment.

Proton pump inhibitors and the risk of pneumonia: a comparison of cohort and self-controlled case series designs

BackgroundTo compare the results of a new-user cohort study design and the self-controlled case series (SCCS) design using the risk of hospitalisation for pneumonia in those dispensed proton pump inhibitors compared to those unexposed as a case study.MethodsThe Australian Government Department of Veterans’ Affairs administrative claims database was used. Exposure to proton pump inhibitors and hospitalisations for pneumonia were identified over a 4 year study period 01 Jul 2007 -30 Jun 2011. The same inclusion and exclusion criteria were applied to both studies, however, the SCCS study included subjects with a least one hospitalisation for pneumonia.ResultsThere were 105,467 subjects included in the cohort study and 6775 in the SCCS. Both studies showed an increased risk of hospitalisations for pneumonia in the three defined risk periods following initiation of proton pump inhibitors compared to baseline. With the highest risk in the first 1 to 7 days (Cohort RR, 3.24; 95% CI (2.50, 4.19): SCCS: RR, 3.07; 95% CI (2.69, 3.50)).ConclusionsThis study has shown that the self-controlled case series method produces similar risk estimates to a new-users cohort study design when applied to the association of proton pump inhibitors and pneumonia. Exposure to a proton pump inhibitor increases the likelihood of being admitted to hospital for pneumonia, with the risk highest in the first week of treatment.

Naive Hypothesis Testing for Case Series Analysis with Time‐Varying Exposure Onset Measurement Error: Inference for Infection‐Cardiovascular Risk in Patients on Dialysis

The case series method is useful in studying the relationship between time-varying exposures, such as infections, and acute events observed during the observation periods of individuals. It provides estimates of the relative incidences of events in risk periods (e.g., 30-day period after infections) relative to the baseline periods. When the times of exposure onsets are not known precisely, application of the case series model ignoring exposure onset measurement error leads to biased estimates. Bias-correction is necessary in order to understand the true directions and effect sizes associated with exposure risk periods, although uncorrected estimators have smaller variance. Thus, inference via hypothesis testing based on uncorrected test statistics, if valid, is potentially more powerful. Furthermore, the tests can be implemented in standard software and do not require additional auxiliary data. In this work, we examine the validity and power of naive hypothesis testing, based on applying the case series analysis to the imprecise data without correcting for the error. Based on simulation studies and theoretical calculations, we determine the validity and relative power of common hypothesis tests of interest in case series analysis. In particular, we illustrate that the tests for the global null hypothesis, the overall null hypotheses associated with all risk periods or all age effects are valid. However, tests of individual risk period parameters are not generally valid. Practical guidelines are provided and illustrated with data from patients on dialysis.

A simulation study to compare three self‐controlled case series approaches: correction for violation of assumption and evaluation of bias

The assumption that the occurrence of outcome event must not alter subsequent exposure probability is critical for preserving the validity of the self-controlled case series (SCCS) method. This assumption is violated in scenarios in which the event constitutes a contraindication for exposure. In this simulation study, we compared the performance of the standard SCCS approach and two alternative approaches when the event-independent exposure assumption was violated. Using the 2009 H1N1 and seasonal influenza vaccines and Guillain-Barré syndrome as a model, we simulated a scenario in which an individual may encounter multiple unordered exposures and each exposure may be contraindicated by the occurrence of outcome event. The degree of contraindication was varied at 0%, 50%, and 100%. The first alternative approach used only cases occurring after exposure with follow-up time starting from exposure. The second used a pseudo-likelihood method. When the event-independent exposure assumption was satisfied, the standard SCCS approach produced nearly unbiased relative incidence estimates. When this assumption was partially or completely violated, two alternative SCCS approaches could be used. While the post-exposure cases only approach could handle only one exposure, the pseudo-likelihood approach was able to correct bias for both exposures. Violation of the event-independent exposure assumption leads to an overestimation of relative incidence which could be corrected by alternative SCCS approaches. In multiple exposure situations, the pseudo-likelihood approach is optimal; the post-exposure cases only approach is limited in handling a second exposure and may introduce additional bias, thus should be used with caution.

Safety of Pandemic (H1N1) 2009 Monovalent Vaccines in Taiwan: A Self-Controlled Case Series Study

In Taiwan, new H1N1 monovalent vaccines without adjuvant and with MF59® adjuvant were used in the nationwide vaccination campaign beginning on November 1, 2009. From November 2009 through February 2010, the authors identified recipients of H1N1 vaccines who were diagnosed with adverse events of special interest (AESIs) in a large-linked safety database, and used the self-controlled case series (SCCS) method to examine the risk of each AESI in the 0–42 days after H1N1 vaccination. Of the 3.5 million doses of H1N1 vaccines administered and captured in the linked database, the SCCS analysis of Guillain-Barré syndrome (GBS) found an incidence rate ratio of 3.81 (95% confidence interval 0.43–33.85) within 0–42 days after nonadjuvanted H1N1 vaccination and no cases after MF59®-adjuvanted H1N1 vaccination. The risks of other AESIs were, in general, not increased in any of the predefined postvaccination risk periods and age groups. The databases and infrastructure created for H1N1 vaccine safety evaluation may serve as a model for safety, effectiveness and coverage studies of licensed vaccines in Taiwan.

The self‐controlled case series method for evaluating safety of vaccines

Using cases as their own controls potentially provides stronger evidence for analysing adverse events following vaccination.

A Positive Event Dependence Model for Self‐Controlled Case Series with Applications in Postmarketing Surveillance

A primary objective in the application of postmarketing drug safety surveillance is to ascertain the relationship between time-varying drug exposures and recurrent adverse events (AEs) related to health outcomes. The self-controlled case series (SCCS) method is one approach to analysis in this context. It is based on a conditional Poisson regression model, which assumes that events at different time points are conditionally independent given the covariate process. This requirement is problematic when the occurrence of an event can alter the future event risk. In a clinical setting, for example, patients who have a first myocardial infarction (MI) may be at higher subsequent risk for a second. In this work, we propose the positive dependence self-controlled case series (PD-SCCS) method: a generalization of SCCS that allows the occurrence of an event to increase the future event risk, yet maintains the advantages of the original model by controlling for fixed baseline covariates and relying solely on data from cases. As in the SCCS model, individual-level baseline parameters drop out of the PD-SCCS likelihood. Data sources used for postmarketing surveillance can contain tens of millions of people, so in this situation it is particularly advantageous that PD-SCCS avoids doing a costly estimation of individual parameters. We develop expressions for large sample inference and optimization for PD-SCCS and compare the results of our generalized model with the more restrictive SCCS approach.

Mortality and the self‐controlled case series method: Letter to the Editor

Mortality and the self‐controlled case series method: Letter to the Editor

Mortality and the self‐controlled case series method. Response to Letter to Editor.

Pharmacoepidemiology and Drug SafetyVolume 21, Issue 8 p. 907-907 Letter to the Editor Mortality and the self-controlled case series method. Response to Letter to Editor. Malcolm Maclure, Corresponding Author Malcolm Maclure [email protected] Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Victoria, BC, CanadaAnesthesiology, Pharmacology & Therapeutics, University of British Columbia, Victoria BC CanadaSearch for more papers by this authorBruce Fireman, Bruce Fireman Division of Research, Kaiser Permanente, Oakland, CA, USASearch for more papers by this authorJennifer Nelson, Jennifer Nelson Biostatistics Unit, Group Health Research Institute, Seattle, WA, USASearch for more papers by this authorDavid Madigan, David Madigan Statistics, Columbia University, New York, NY, USASearch for more papers by this author Malcolm Maclure, Corresponding Author Malcolm Maclure [email protected] Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Victoria, BC, CanadaAnesthesiology, Pharmacology & Therapeutics, University of British Columbia, Victoria BC CanadaSearch for more papers by this authorBruce Fireman, Bruce Fireman Division of Research, Kaiser Permanente, Oakland, CA, USASearch for more papers by this authorJennifer Nelson, Jennifer Nelson Biostatistics Unit, Group Health Research Institute, Seattle, WA, USASearch for more papers by this authorDavid Madigan, David Madigan Statistics, Columbia University, New York, NY, USASearch for more papers by this author First published: 27 July 2012 https://doi.org/10.1002/pds.3286Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue8August 2012Pages 907-907 RelatedInformation

Diagnosis and treatment of depression following routine screening in patients with coronary heart disease or diabetes: a database cohort study

Depression is common in chronic illness and screening for depression has been widely recommended. There have been no large studies of screening for depression in routine care for patients with chronic illness. We performed a retrospective cohort study to examine the timing of new depression diagnosis or treatment in relation to annual screening for depression in patients with coronary heart disease (CHD) or diabetes. We examined a database derived from 1.3 million patients registered with general practices in Scotland for the year commencing 1 April 2007. Eligible patients had either CHD or diabetes, were screened for depression during the year and either received a new diagnosis of depression or commenced a new course of antidepressant (excluding those commonly used to treat diabetic neuropathy). Analysis was by the self-controlled case-series method with the outcome measure being the relative incidence (RI) in the period 1-28 days after screening compared to other times. A total of 67358 patients were screened for depression and 2269 received a new diagnosis or commenced treatment. For the period after screening, the RI was 3.03 [95% confidence interval (CI) 2.44-3.78] for diagnosis and 1.78 (95% CI 1.54-2.05) for treatment. The number needed to screen was 976 (95% CI 886-1104) for a new diagnosis and 687 (95% CI 586-853) for new antidepressant treatment. Systematic screening for depression in patients with chronic disease in primary care results in a significant but small increase in new diagnosis and treatment in the following 4 weeks.

Risk of Guillain-Barré Syndrome Following H1N1 Influenza Vaccination in Quebec

In fall 2009 in Quebec, Canada, an immunization campaign was launched against the 2009 influenza A(H1N1) pandemic strain, mostly using an AS03 adjuvant vaccine. By the end of the year, 57% of the 7.8 million residents had been vaccinated. To assess the risk of Guillain-Barré syndrome (GBS) following pandemic influenza vaccine administration. Population-based cohort study with follow-up over the 6-month period October 2009 through March 2010. The investigation was ordered by the chief medical officer of health in accordance with the Quebec Public Health Act. All acute care hospitals and neurology clinics in Quebec. Suspected and confirmed GBS cases reported by physicians, mostly neurologists, during active surveillance or identified in the provincial hospital summary discharge database. Medical records were reviewed and cases classified according to Brighton Collaboration definitions (categorized as level 1, 2, or 3, corresponding to criteria of decreasing certainty in diagnosis). Immunization status was verified and denominators were estimated from the provincial immunization registry (4.4 million vaccinated) and census data (total target population aged ≥6 months, 7.8 million), with a total of 3,623,046 person-years of observation. Relative and attributable risks were calculated using a Poisson model and the self-controlled case-series method. Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8-week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64-5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years. In Quebec, the 2009 influenza A(H1N1) vaccine was associated with a small but significant risk of GBS. It is likely that the benefits of immunization outweigh the risks.