Development and validation of algorithms for identifying lines of therapy in multiple myeloma using real-world data.

Aim: To validate algorithms based on electronic health data to identify composition of lines of therapy (LOT) in multiple myeloma (MM). Materials & methods: This study used available electronic health data for selected adults within Henry Ford Health (Michigan, USA) newly diagnosed with MM in 2006-2017. Algorithm performance in this population was verified via chart review. As with prior oncology studies, good performance was defined as positive predictive value (PPV) ≥75%. Results: Accuracy for identifying LOT1 (N = 133) was 85.0%. For the most frequent regimens, accuracy was 92.5-97.7%, PPV 80.6-93.8%, sensitivity 88.2-89.3% and specificity 94.3-99.1%. Algorithm performance decreased in subsequent LOTs, with decreasing sample sizes. Only 19.5% of patients received maintenance therapy during LOT1. Accuracy for identifying maintenance therapy was 85.7%; PPV for the most common maintenance therapy was 73.3%. Conclusion: Algorithms performed well in identifying LOT1 - especially more commonly used regimens - and slightly less well in identifying maintenance therapy therein.

Electronic health data helps us understand treatment in the 'real world'. The data has great value in cancer if we can identify the drugs patients get. Yet this is hard in multiple myeloma (MM), where treatment is complex. Algorithms (set of decision rules) to identify drugs can help here. We tested an existing algorithm for identifying 'lines of therapy' (LOT) given to patients with MM. Each LOT included one or more drugs for MM. We also developed and tested a new algorithm for 'maintenance therapy'. This is a treatment given to help maintain the response to the main MM treatment. We tested how well the algorithms identified MM treatments in electronic health data. This data came from Henry Ford Health, a healthcare system in Michigan, USA. Treatments were confirmed by cancer specialists who reviewed medical charts. The LOT algorithm was good at finding the first LOT patients. The maintenance algorithm did a fair job of identifying the most used therapy. Our algorithms could help researchers study the real-world treatment of MM.

Pneumonia hospitalizations of children aged <2 years in Poland before (2013-2016) and after (2017-2018) universal mass vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine.

As infection with Streptococcus pneumoniae is an important cause of pneumonia in children, the World Health Organization recommends childhood pneumococcal conjugate vaccines (PCVs). In January 2017, PCV universal mass vaccination (UMV) was introduced in Poland for children aged <2 years. The objective of this study was to estimate and describe the trends in the incidences of various types of pneumonia hospitalizations in Poland before (2013-2016) and after (2017-2018) introduction of the UMV program. The study was conducted at the regional hospitals of Opole and Bialystok and included all hospitalized children aged <2 years with a primary or secondary diagnosis of pneumonia in their electronic medical records. Pneumonia diagnoses were identified based on International Classification of Diseases 10th revision (ICD-10) codes for bacterial, viral, and other/unknown-cause pneumonias. The effect of the implementation of PCV UMV was modeled via an inferential multivariate model. Among 4,168 children included in the study, 64.3% were admitted before PCV UMV. The number of radiograph-confirmed likely bacterial pneumonia cases varied between 55 and 176 cases per 100,000 person-years, and no trend was observed over time. However, inferential modeling showed statistically significant decreasing trends in the incidence rates of bacterial-coded pneumonia (28.48%), viral-coded pneumonia (35.36%), all-cause pneumonia (24.60%), and radiograph-confirmed likely non-bacterial pneumonia (24.98%) among children eligible for UMV. This might be the first indication of the impact of the PCV UMV program in Poland.

What is the context? Infection with the bacteria Streptococcus pneumoniae is a key cause of pneumonia in children worldwide.Pneumococcal vaccines are available to help prevent this infection.In 2017, a pneumococcal vaccination program was introduced in Poland, free of charge for children aged less than 2 years.The impact of this vaccination program on the incidence of pneumonia hospitalizations is unknown.What is new? This study evaluated the incidence of pneumonia hospitalizations in children following the implementation of the vaccination program (2017-2018) and compared it with the incidence before implementation (2013-2016).The study was carried out in two regional hospitals and included all children aged less than 2 years hospitalized with pneumonia.Pneumonia cases were identified using International Classification of Diseases codes and bacterial cases were confirmed with chest x-rays.During the 2 years after the vaccination program was introduced, we observed:No clear trend in the incidence of bacterial pneumonia confirmed by chest x-ray.A statistically significant decline in the likelihood of developing other types of pneumonia among children eligible for the pneumococcal vaccination program.The incidence of pneumonia was higher in children from the region of Opole and for those who were admitted to hospital in winter and at a younger age.What is the impact? Pneumococcal vaccination might reduce the number of pneumonia hospitalizations. However, more research is needed to confirm these results.

Nivolumab in gastric/gastroesophageal junction cancer: real-world data from UK Early Access to Medicines Scheme.

Aim: This study provides real-world insight into patient profile, clinical effectiveness and health-related quality of life among patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma treated with nivolumab. Materials & methods: Data were collected from medical records of patients with advanced GEJ adenocarcinoma treated with nivolumab in a UK Early Access to Medicines Scheme and from the patient-reported EuroQoL five dimensions questionnaire. Results: Evaluable patients (n = 113; median age 62 years) were predominantly male (76.1%), White (87.4%) and with GEJ adenocarcinoma (61.9%). Median follow-up was 2.8 months. The 6-month progression-free survival and overall survival were 31.6 and 56.7%, respectively. Mean EuroQoL five dimensions questionnaire index utility scores at baseline, 8, 16 and 24 weeks were 0.795, 0.831, 0.870 and 0.793, respectively. Conclusion: Progression-free survival was consistent with trial results and health-related quality of life remained stable over time.

Lay abstract This study looked at the characteristics and quality of life (QoL) of patients who were taking the drug, nivolumab, and how well it works for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. GEJ adenocarcinoma is a rare type of cancer that starts in the GEJ, the area where the esophagus and stomach join. Information was collected from the medical records of patients who had advanced GEJ adenocarcinoma and were treated with nivolumab as part of a UK program that gives people access to new treatments that are not yet licensed. Patients also filled out a questionnaire called the EuroQoL five dimensions questionnaire that focuses on a patient's quality of life (QoL). In total, 113 patients were a part of the study. The midpoint of all patients' ages was 62 years and they were mostly males (76.1%), Whites (87.4%) and with GEJ adenocarcinoma (61.9%). The midpoint of follow-up time was 2.8 months. The percentages of patients meeting progression-free survival for 6 months, a period when a patient lives with GEJ adenocarcinoma but it does not get worse, and overall survival were 31.6 and 56.7%, respectively. Mean EuroQoL five dimensions questionnaire index scores (comprised between zero and one, the higher the better) at treatment start, 8, 16 and 24 weeks were 0.795, 0.831, 0.870 and 0.793, respectively. Progression-free survival was similar to clinical trial results and QoL was constant over time.

Genetic Testing in Natural History Studies: A Review of the Regulatory and Legal Landscape.

BACKGROUND: Natural history (NH) studies, using observational methods, are common in rare and orphan diseases (80% of which have a genetic component). There is profound interest in identifying genetic mutations driving these diseases in these studies to support the formulation of targeted precision medicines. The global regulatory classification of NH studies with novel molecular biomarker collection has not been clearly delineated, presenting researchers with the challenge of determining how these studies are classified and regulated across multiple geographies. OBJECTIVE: The aim of this investigation was to conduct a review of regulations related to NH studies and genetic testing to elucidate regulatory pathways to inform clinical researchers in the field. METHODS: Regulatory provisions for NH studies and genetic testing were obtained from Pharmaceutical Product Development (PPD)'s propriety regulatory intelligence database and by surveying the company's country-specific regulatory experts. A literature search was conducted in the Google Scholar search engine and PubMed for supplementary information. RESULTS: Nineteen countries were evaluated; 37% classified NH studies with biomarker collection as noninterventional and 26% required regulatory approval (increasing to 47% when molecular biomarker testing was introduced). No regulatory provisions for genetic testing could be identified in 32% of countries, and 58% did not have binding requirements for genetic counseling. CONCLUSION: Lack of harmonization of regulations governing NH studies with molecular biomarker collection contributes to the operational complexity of conducting multinational studies in orphan and rare diseases. A set of harmonized international guidelines for these studies would improve efficiency, and this may be on the horizon with the recent adaption of International Conference on Harmonisation (ICH) guideline E18.

Patient-reported depression severity and cognitive symptoms as determinants of functioning in patients with major depressive disorder: a secondary analysis of the 2-year prospective PERFORM study.

PURPOSE: To investigate the temporal interrelationship between depression severity, cognitive symptoms, and functioning in patients with major depressive disorder (MDD) in the PERFORM study (NCT01427439). PATIENTS AND METHODS: PERFORM was a 2-year, multicenter, prospective, noninterventional cohort study in outpatients with MDD who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Patients were enrolled by a general practitioner or psychiatrist. Structural equation model (SEM) analysis was used to explore temporal associations between patient-reported depression severity (9-item Patient Health Questionnaire score), cognitive symptoms (5-item Perceived Deficits Questionnaire score), and functional impairment (Sheehan Disability Scale total score). Standardized regression coefficients (SRCs) were used to evaluate the relationship between each outcome and scores from the most recent prior visit over the 2 years of follow-up. RESULTS: Between February 25, 2011, and February 19, 2015, 1,159 eligible patients with MDD completed the baseline and ≥1 follow-up visit at 194 sites in five European countries (France, Germany, Spain, Sweden, and the UK). Overall, 1,090 patients had assessments for ≥1 outcome measure at two consecutive visits. Severity of cognitive symptoms at baseline and Months 2 and 18 predicted functional impairment at Months 2, 6, and 24, respectively (SRC: 0.18, 0.15, and 0.22; P<0.001). Depression severity at Months 2, 6, and 12 predicted functional impairment at Months 6, 12, and 18, respectively (SRC: 0.17, 0.25, and 0.22; P<0.001). Severity of cognitive symptoms at baseline and Month 18 predicted depression severity at Months 2 and 24, respectively (SRC: 0.19 and 0.22; P<0.001). Functional impairment did not significantly predict the severity of depression or cognitive symptoms, and depression severity did not significantly predict the severity of cognitive symptoms at any time point. CONCLUSION: Patient-reported severity of cognitive symptoms appears to be an independent and significant determinant of subsequent functional impairment and depression severity in patients with MDD.

Creation and validation of a linear index to measure the health state of patients with depression in automated healthcare databases.

Background and objective: We previously built a weighted Depressive Health State Index (DHSI) based on 29 parameters routinely collected in an automated healthcare database (AHDB). We now propose a linear DHSI (L-DHSI) which is easier to use and to replicate across AHDBs. Methods: A historical cohort of patients with ≥1 episode of depression was identified in the Clinical Practice Research Datalink (CPRD). The DHSI was calculated for each treated episode of depression. Validation was performed by using validated definitions of remission (proxy and Patient Health Questionnaire 9 or PHQ-9) and comparing the L-DHSI between subgroups. Reliability was assessed using Cronbach's alpha. Results: Between 1 January 2006 and 31 December 2012, 309,279 episodes of depression were identified in the CPRD. Remission was observed in 5% of the patients with lowest L-DHSI scores and in 78% of the patients with highest L-DHSI scores. Although less sensitive than the weighted DHSI, the L-DHSI was reliable and relatively easy of use. The L-DHSI was highly correlated to the weighted DHSI (Spearman coefficient 0.790, p < 0.001). Conclusion: The L-DHSI represents a good balance between reliability, usability, and reproducibility. In addition, the linearity of this index allows for an easier interpretation than the original weighted DHSI.

Results and validation of an index to measure health state of patients with depression in automated healthcare databases.

Background and objective: A Depressive Health State Index (DHSI) based on 29 parameters routinely collected in an automated healthcare database (AHDB) was developed to evaluate the health state of depressive patients, and its evolution. The study objective was to describe and validate this DHSI. Methods: A historical cohort of patients with at least one episode of depression was identified in the Clinical Practice Research Datalink (CPRD). The DHSI was calculated for each episode of depression. Validation was performed by comparing the DHSI between subgroups and using validated definitions of remission (proxy and PHQ-9). Robustness was studied by assessing the impact of modifying parameters of the DHSI. Results: 309,279 episodes of depression were identified in the CPRD between 1 January 2006 and 31 December 2012. Remission was observed in 8% of the patients showing the lower DHSI scores and in 88% of the patients showing the higher DHSI scores. The DHSI was robust to a modification of the most frequent variables and to the removal of rare parameters. Conclusion: The DHSI is specific to depression severity (with remission rates in accordance with the expected variations of the DHSI) and robust. It represents a promising tool for the analysis of AHDBs.

Psychometric validation of the Perceived Deficits Questionnaire-Depression (PDQ-D) instrument in US and UK respondents with major depressive disorder.

BACKGROUND: Although depression and cognitive dysfunction are connected, limited tools exist to capture the patient's perspective on cognitive dysfunction and its impact on major depressive disorder (MDD). We report results of a psychometric validation of the Perceived Deficits Questionnaire-Depression (PDQ-D), a self-report measure of cognitive dysfunction for use in MDD. METHODS: A non-interventional, prospective, panel-recruited, online survey was conducted using the PDQ-D in adults with and without MDD in the US and UK. Respondents were assessed at baseline and after 6 weeks (MDD only) (baseline: US n=418, UK n=437, 49% MDD; follow-up: US n=169, UK n=153, all MDD). The criterion measures included: Medical Outcomes Study Cognitive Functioning Scale-Revised-acute form (MOS COG-R), Patient Health Questionnaire-9 (PHQ-9), Patient Global Impression of Severity scale (PGI-Severity), Sheehan Disability Scale (SDS), Work Productivity and Activity Impairment Questionnaire: Specific-Health Problem (WPAI:SHP), and modified Lam Employment Absence and Productivity Scale (LEAPS). US and UK data were analyzed separately. RESULTS: Internal consistency was high for PDQ-D total scale and four subscales (Cronbach's alpha 0.81-0.96). Convergent validity was good, with strong concordance with MOS COG-R and moderate/small correlations with PHQ-9, SDS, WPAI:SHP, LEAPS, and PGI-Severity. Significant differences (all P<0.001) existed for all PDQ-D subscale and total scores between MDD/non-MDD samples. The PDQ-D was responsive to changes in depression symptom severity. Confirmatory factor analysis supported scoring of a global overall scale for perceived cognitive dysfunction. CONCLUSION: The PDQ-D provides a reliable and valid measure of subjective cognitive dysfunction in patients with MDD.

Long-term follow-up on health-related quality of life in major depressive disorder: a 2-year European cohort study.

BACKGROUND: Major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQoL) and everyday functioning. This cohort study investigated the long-term development of HRQoL in patients with MDD and its association with patient characteristics, including depressive symptom severity and cognitive symptoms. METHODS: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study was a longitudinal cohort study conducted in 1,159 outpatients aged 18-65 years with MDD in France, Germany, Spain, Sweden, and the UK. The patients were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. HRQoL was assessed using the Medical Outcomes Study Short-Form 12-item Health Survey (SF-12) up to month 12 and the EuroQol Five Dimensions questionnaire up to month 24 (UK only). Depressive symptom severity was assessed up to month 24 by the patient-reported Patient Health Questionnaire and cognitive symptoms by the Perceived Deficit Questionnaire. Multivariate analyses were performed to identify patient characteristics associated with HRQoL. RESULTS: Mental HRQoL was severely impaired at baseline versus normative data (mean [SD] SF-12 mental component summary [MCS], 26.5 [9.2]); mean (SD) physical component summary (PCS) total score was 45.2 (12.1). SF-12 MCS improved over 12 months of follow-up (38.7 [11.6] at month 12), while SF-12 PCS remained stable (45.3 [11.1]). At each assessment time point, there was a clear pattern of lower SF-12 MCS and PCS total score in patients experiencing greater cognitive problems. The mean EuroQol Five Dimensions questionnaire utility index score generally decreased (i.e., worsened) with increasing severity of cognitive and depressive symptoms at all time points up to 24 months. Multivariate analyses identified both depression severity and cognitive symptoms as strongly and significantly associated with poor HRQoL. CONCLUSION: These findings highlight the importance of recognizing and managing residual symptoms in patients with MDD, including the cognitive symptoms, to restore long-term psychosocial functioning.

Characteristics of patients with depression initiating or switching antidepressant treatment: baseline analyses of the PERFORM cohort study.

BACKGROUND: Patients who require a switch in their antidepressant therapy may have different clinical profiles and treatment needs compared with patients initiating or maintaining a first-line antidepressant therapy. METHODS: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (MDD) (PERFORM) study was a 2-year observational cohort study in outpatients with MDD in five European countries. Enrolled patients were either initiating or undergoing the first switch to an antidepressant monotherapy. Baseline data on patients' clinical status, functioning, productivity, quality of life and medical-resource use were compared in a cross-sectional baseline analysis. RESULTS: A total of 1402 patients were enrolled, of whom 1159 (82.7%) provided analysable baseline data. The majority (78.7%) of the analysable population were initiating antidepressant treatment and most (83.6%) were enrolled and followed up by general practitioners. Compared with patients initiating antidepressants, those switching antidepressants (21.3%) tended to have more severe depressive symptoms, greater anxiety, worse health-related quality of life, greater functional impairment, greater medical-resource use and had a different medical history. Limitations included an over-representation of switches due to lack of efficacy among patients who were switching treatment, as patients were selected based on presence of depressive symptoms. CONCLUSIONS: Patients with MDD who are switching treatment for the first time have a different profile and different depression-associated health needs compared with those initiating treatment. Therapeutic management should therefore be adapted for patients who switch. TRIAL REGISTRATION: ClinicalTrials.gov NCT01427439 ; Retrospectively registered 26 August 2011.

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study.

BACKGROUND: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. METHODS: This was a 2-year observational study in 1,159 outpatients with MDD aged 18-65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. RESULTS: The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. CONCLUSION: These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice.

Creating an index to measure health state of depressed patients in automated healthcare databases: the methodology.

Background and objective: Automated healthcare databases (AHDB) are an important data source for real life drug and healthcare use. In the filed of depression, lack of detailed clinical data requires the use of binary proxies with important limitations. The study objective was to create a Depressive Health State Index (DHSI) as a continuous health state measure for depressed patients using available data in an AHDB. Methods: The study was based on historical cohort design using the UK Clinical Practice Research Datalink (CPRD). Depressive episodes (depression diagnosis with an antidepressant prescription) were used to create the DHSI through 6 successive steps: (1) Defining study design; (2) Identifying constituent parameters; (3) Assigning relative weights to the parameters; (4) Ranking based on the presence of parameters; (5) Standardizing the rank of the DHSI; (6) Developing a regression model to derive the DHSI in any other sample. Results: The DHSI ranged from 0 (worst) to 100 (best health state) comprising 29 parameters. The proportion of depressive episodes with a remission proxy increased with DHSI quartiles. Conclusion: A continuous outcome for depressed patients treated by antidepressants was created in an AHDB using several different variables and allowed more granularity than currently used proxies.

Factors associated with failure to achieve remission and with relapse after remission in patients with major depressive disorder in the PERFORM study.

BACKGROUND: The Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder (PERFORM) study has been initiated to better understand the course of a depressive episode and its impact on patient functioning. This analysis aimed to identify sociodemographic and clinical factors associated with failure to achieve remission at month 2 after initiating or switching antidepressant monotherapy and with subsequent relapse at month 6 for patients in remission at month 2. MATERIALS AND METHODS: This was a 2-year observational cohort study in 1,159 outpatients aged 18-65 years with major depressive disorder initiating or undergoing the first switch of antidepressant monotherapy. Factors with P<0.20 in univariate logistic regression analyses were combined in a multiple logistic regression model to which backward variable selection was applied (ie, sequential removal of the least significant variable from the model and recomputation of the model until all remaining variables have P<0.05). RESULTS: Baseline factors significantly associated with lower odds of remission at month 2 were body-mass index ≥30 kg/m2 (OR 0.51), depressive episode >8 weeks (OR 0.51), being in psychotherapy (OR 0.51), sexual dysfunction (OR 0.62), and severity of depression (OR 0.87). Factors significantly associated with relapse at month 6 were male sex (OR 2.47), being married or living as a couple (OR 2.73), residual patient-reported cognitive symptoms at 2 months (OR 1.12 per additional unit of Perceived Deficit Questionnaire-5 score) and residual depressive symptoms at 2 months (OR 1.27 per additional unit of Patient Health Questionnaire-9 score). CONCLUSION: Different factors appear to be associated with failure to achieve remission in patients with major depressive disorder and with subsequent relapse in patients who do achieve remission. Patient-reported cognitive dysfunction is an easily measurable and treatable characteristic that may be associated with an increased likelihood of relapse at 6 months in patients who have achieved remission.

Depressed older adults may be less cared for than depressed younger ones.

The aim of the study was to investigate depression treatment use, either psychotherapy (PT) or antidepressant drugs (ADT) in the older and younger depressed population. Cohorts of 6316 elderly (≥65 year-old) and 25,264 matched non-elderly (25-64 year-old) depressed patients were created from a large national claims database of managed care plans from 2003 to 2006. Factors associated with ADT or PT were assessed using multivariate logistic models. During the 120 days following the depression diagnosis, the elderly persons were less often treated than the younger adults either by ADT (25.6% vs. 33.8%) or by PT (13.0% vs. 34.4%). ADT dispensing occurred later in the elderly group (51 vs. 14 days). ADT was associated with comorbid chronic conditions or polypharmacy in the elderly and younger adults. The selection of treatment (ADT or PT) was associated with the history of treated depression using the same type of treatment, in both groups. Thus, depression goes commonly untreated. Comorbidity was associated with higher ADT dispensing rates. However, although depressed elderly commonly presented with comorbidity, this age group was at higher risk of untreated illness or later treatment.

A clinical research practice datalink analysis of antidepressant treatment patterns and health care costs in generalized anxiety disorder.

OBJECTIVE: To describe real-life prescription patterns, health care resource use, and costs in adults with generalized anxiety disorder (GAD) initiating antidepressant (AD) treatment in the United Kingdom. METHODS: A retrospective longitudinal cohort study using data from Clinical Research Practice Datalink was conducted. Adults with incident prescription of an AD (index date) between January 1, 2006, and June 30, 2010, and with a diagnosis of GAD within the 2 months preceding or following the index date were included. Patients with a diagnosis of schizophrenia or bipolar disorder were excluded. RESULTS: A total of 29,131 patients with GAD were included in the analysis. Their mean age was 48.5 ± 15.5 years, and two thirds were women. GAD-licensed ADs (i.e., escitalopram, paroxetine, venlafaxine XR, and duloxetine) represented only 12.5% of the index AD prescriptions. At least one anxiolytic was prescribed for 23.5% of the patients. Only 33.2% of the patients continued index AD treatment over the study period. Discontinuation occurred for 46.0% of the patients, after a mean of 3.7 months of treatment. The health care costs were £338.4 per patient in the 6 months before the index date and £984.6 in the 9 months after the index date. Psychiatric hospitalization (relative risk = 4.18; 95% CI 3.53-4.96; P < 0.001) and duloxetine as index treatment (relative risk = 1.85; 95% CI 1.30-2.63; P < 0.001) were the main determinants of increased costs for these patients. CONCLUSIONS: The significant rate of AD discontinuation and associated treatment duration indicate unmet needs among patients with GAD. As described in American studies, substantial health care costs were also observed in this study.

Pattern and predictors of sick leave among users of antidepressants: a Danish retrospective register-based cohort study.

OBJECTIVES: Depression is associated with work absenteeism, reduced productivity, and significant personal and societal economic burden. We describe patterns and determinants of sick leave among working Danish antidepressant users. METHODS: Persons starting antidepressant treatment (January 1, 2004 through December 31, 2005) were identified from a representative 25% sample of the Danish population by linking Danish national registries. Inclusion criteria were age 18-64 years, being in the workforce the week prior to the first antidepressant prescription (index prescription, IP), and no antidepressant prescription in the year prior to the IP. Only sick leaves >2 weeks are centrally registered in Denmark and could be assessed. Cox regression analyses identified predictors of sick leave during the year following the IP, based on previous history of sick leave and clinical and socio-demographic baseline characteristics. RESULTS: In the cohort of 25,908 (59.7% women), sick leave prevalence increased from 37.5% (year prior to IP) to 45.3% (year after the IP); 30.7% were on sick leave for >8 weeks. Incidence peaked (35.5% of individuals) the week after the IP. Of persons with sick leave in the year before the IP, 62.7% were on sick leave the first week after the IP, vs 5.7% of those without previous sick leave. Predictors associated with increased risk of sick leave among those without previous sick leave were unemployment, female gender, age 25-54 years, couples with children, and vocational and higher intermediate education (including e.g. teachers and nurses). LIMITATIONS: Reasons for sick leave, sick leaves of less than 14 days and the indications for antidepressant treatment were unknown. CONCLUSIONS: Sick leave was prevalent in persons starting new antidepressant use, often lasting >8 weeks. Previous sick leave was the strongest predictor of subsequent sick leave.

Comparing antidepressant treatment patterns in older and younger adults: a claims database analysis.

OBJECTIVES: To compare depressed older (≥65) and younger (25-64) adults with regard to antidepressant treatment patterns and to assess factors associated with 180-day nonpersistence. DESIGN: Retrospective matched cohort study. SETTING: U.S. managed care population. PARTICIPANTS: Older and matched younger adults diagnosed with depression and treated with antidepressants. MEASUREMENTS: Sociodemographic characteristics, comorbidities, polypharmacy, and characteristics of antidepressant treatment at 180 days were compared between older and younger adults. Analyses were conducted before and after the implementation of Medicare Part D on January 1, 2006, to consider the effect of this policy. RESULTS: Few participants received psychotherapy, especially older ones; rates were constant before and after 2006. Before 2006, older adults more frequently received antidepressants at lower (odds ratio (OR)=5.38, 95% confidence interval (CI)=3.57-8.13) or intermediate dose (OR=2.42, 95% CI=1.93-3.02) and had poorer adherence to treatment (P<.001) than younger adults. After 2006, older adults received similar proportions of intermediate or high antidepressant doses as younger adults, but a lower dosage was still more likely to be prescribed (OR=1.87, 95% CI=1.09-3.20) and had higher treatment adherence (P<.001). Medication profile did not significantly affect the risk of nonpersistence, but increased with lower antidepressant dose (P<.001). Whereas nonpersistence was higher in older adults before 2006 (hazard ratio (HR)=1.25, 95% CI=1.22-1.46), the trend reversed after 2006 (HR=0.76, 95% CI=0.66-0.88). CONCLUSION: More than half of participants with depression discontinued antidepressant treatment, and psychotherapy was rarely used. Implementation of Medicare Part D was associated with substantial changes in treatment of older adults with depression. The presence of comorbidities or polypharmacy was not associated with nonpersistence in depressed older adults.

The 6-month persistence on SSRIs and associated economic burden.

OBJECTIVES: To assess persistence on SSRIs (most prescribed antidepressants) and associated healthcare costs in a naturalistic setting. METHODS: For this retrospective cohort study based on a US reimbursement claims database, all adults with a claim for a SSRI (citalopram, escitalopram, fluoxetine, paroxetine or sertraline) related to a diagnosis of depression were included. Patients should have had no previous reimbursement for any antidepressant within the previous 6 months. Non-persistence was defined as failing to renew prescription within 30 days in the 6-month period after the index date. RESULTS: In the 45,481 patients included, persistence decreased from 95.5% at 1 month, to 52.6% at 2 months, 37.6% at 3 months and 18.9% at 6 months. Among factors associated with higher 6-month persistence were age 18-34 years, physician's specialty, treatment with escitalopram, absence of abuse history and psychotropic prescription history. During the 6-month after index date, healthcare costs tended to be higher in non-persistent than in persistent patients although not significantly (RR=1.05, adjusted p=0.055). CONCLUSION: Despite some limitations associated with the use of computerized administrative claims data (residual unmeasured confounding), these results highlight a generally low persistence rate at 6 months. Special attention should be given to persistence on treatment, with consideration of potential antidepressant impact.

Modeling stroke management: a qualitative review of cost-effectiveness analyses.

OBJECTIVE: To review recent economic analyses and determine if means of improving methodology used in modeling stroke management may exist. STUDY DESIGN AND SETTING: The Medline database was searched for pharmacoeconomic models of treatments or interventions in acute, non-transitory ischemic stroke. Search terms were: stroke, cost, cost-effectiveness, cost analysis, stroke management, model, modeling, and economic. All English-language articles published from January 1997 to January 2008 were reviewed. RESULTS: Ten Markov models and three decision analytical models were identified. All models had a societal perspective and all but one had lifetime horizons. They were all based on common patient states of disability, mortality and recurrence of stroke. Inputs used in the models were transparent and valid. Intracranial hemorrhage, cardiovascular events and data closely related to local settings were not systematically considered. One-way sensitivity analyses were the most common, but few parameters were tested and these varied between models. Consensus key drivers were therefore difficult to determine. CONCLUSION: The overall structure of the models reviewed was sound. However, they should include more systematically cardiovascular events and intracranial hemorrhage, as well as local epidemiological data. Further multi-way sensitivity analyses would help to identify key cost drivers with greater precision and robustness.

Healthcare expenditure in severely depressed patients treated with escitalopram, generic SSRIs or venlafaxine in the UK.

OBJECTIVE: To retrospectively compare the 12-month healthcare utilisation and direct medical costs associated with the use of escitalopram, generic SSRIs, and venlafaxine in patients with severe depression in the United Kingdom (UK). METHODS: Data for this retrospective cohort study were extracted from the GPRD, a large primary care database in the UK. Data from adults with an incident prescription of escitalopram, venlafaxine, or generic SSRI were extracted. The initial prescription had to fall within 3 months of a physician visit when severe depression according to the GPRD definition was mentioned. Frequency of antidepressant treatment, GP consultations, referrals, hospitalisations, and concomitant psychiatric medication was assessed on the 12-months after initial prescription and 2006 unit costs for healthcare services obtained from published literature were applied, and then compared between treatment cohorts using a propensity score-adjusted generalised linear model. RESULTS: The total annual healthcare expenditure per patient was similar with escitalopram and generic SSRIs (916 pounds vs. 974 pounds, adjusted p = 0.48) and significantly lower than venlafaxine (916 pounds vs. 1367 pounds, adjusted p < 0.0001), a pattern repeated when antidepressant costs were excluded from the analysis (escitalopram vs. SSRIs, 831 pounds vs. 957 pounds, adjusted p = 0.10; escitalopram vs. venlafaxine, 831 pounds vs. 1156 pounds, adjusted p = 0.006). Over the 12-month analysis period, there were significantly fewer hospitalisations per patient in the escitalopram vs. venlafaxine (0.12 vs. 0.27; adjusted p = 0.01) or generic SSRI (0.12 vs. 0.19; adjusted p = 0.046) groups. CONCLUSION: Despite some limitations associated with the system of data collection in the GPRD (need to apply proxies for severity assessment and external unit costs to resource consumption), the results of this real-life study brings additional evidence of escitalopram appearing to be a cost-effective treatment for patients suffering from severe depression as diagnosed in routine practice and could be considered for first-line treatment in these patients.