Summary of the 12 Most Common Cancers in the CancerLinQ Discovery (CLQD) Database.

PURPOSE: In 2014, the ASCO developed CancerLinQ (CLQ), a health technology platform for oncology. The CLQ Discovery (CLQD) database was created to make data available for research and this paper provides a summary of this database. METHODS: This study described the clinical and demographic characteristics of the 12 most common cancers in the CLQD database. We included patients with a new malignant tumor diagnosis between January 1, 2013, and December 31, 2018, of the following cancers: breast, lung and bronchus, prostate, colon and rectum, melanoma of the skin, bladder, non-Hodgkin lymphoma, kidney and renal pelvis, uterus, leukemia, pancreas, and thyroid. Patients with an in-situ diagnosis were excluded. Summary statistics and Kaplan-Meier survival estimates were calculated for each tumor. RESULTS: From 2013 to 2018, 491,360 patients were diagnosed with the study tumors. Breast cancer (139,506) was the most common, followed by lung and bronchus (70,959), prostate (63,303), and colon and rectum (53,504). The median age at diagnosis (years) was 61, 68, 68, and 64 in breast, lung and bronchus, prostate, and colon and rectum cohorts, respectively. Compared to the SEER 5-year overall survival estimates for several tumor types were higher in the CLQD database, possibly because of incomplete mortality capture in electronic health records. CONCLUSION: This paper presents the first description of the CLQD database since its inception. CLQ will continue to evolve over time, and the breadth and depth of this data asset will continue to grow. ASCO and CLQ's long-term goal is to improve the quality of patient care and create a sustainable database for oncology researchers. These results demonstrate that CLQ built a scalable database that can be used for oncology research.

Characteristics, Symptom Severity, and Experiences of Patients Reporting Chronic Kidney Disease in the PatientsLikeMe Online Health Community: Retrospective and Qualitative Study.

BACKGROUND: Chronic kidney disease (CKD) is a major global health burden, and is associated with increased adverse outcomes, poor quality of life, and substantial health care costs. While there is an increasing need to build patient-centered pathways for improving CKD management in clinical care, data in this field are scarce. OBJECTIVE: The aim of this study was to understand patient-reported experiences, symptoms, outcomes, and treatment journeys among patients with CKD through a retrospective and qualitative approach based on data available through PatientsLikeMe (PLM), an online community where patients can connect and share experiences. METHODS: Adult members (aged ≥18 years) with self-reported CKD within 30 days of enrollment, who were not on dialysis, and registered between 2011 and 2018 in the PLM community were eligible for the retrospective study. Patient demographics and disease characteristics/symptoms were collected from this retrospective data set. Qualitative data were collected prospectively through semistructured phone interviews in a subset of patients, and questions were oriented to better understand patients' experiences with CKD and its management. RESULTS: The retrospective data set included 1848 eligible patients with CKD, and median age was 56 years. The majority of patients were female (1217/1841, 66.11%) and most were US residents (1450/1661, 87.30%). Of the patients who reported comorbidities (n=1374), the most common were type 2 diabetes (783/1374, 56.99%), hypertension (664/1374, 48.33%), hypercholesterolemia (439/1374, 31.95%), and diabetic neuropathy (376/1374, 27.37%). The most commonly reported severe or moderate symptoms in patients reporting these symptoms were fatigue (347/484, 71.7%) and pain (278/476, 58.4%). In the qualitative study, 18 eligible patients (13 females) with a median age of 60 years and who were mainly US residents were interviewed. Three key concepts were identified by patients to be important to optimal care and management: listening to patient needs, coordinating health care across providers, and managing clinical care. CONCLUSIONS: This study provides a unique source of real-world information on the patient experience of CKD and its management by utilizing the PLM network. The results reveal the challenges these patients face living with an array of symptoms, and report key concepts identified by patients that can be used to further improve clinical care and management and inform future CKD studies.

Characteristics and Symptom Severity of Patients Reporting Systemic Lupus Erythematosus in the PatientsLikeMe Online Health Community: A Retrospective Observational Study.

INTRODUCTION: Online health communities and research networks such as PatientsLikeMe (PLM) capture patient perspectives of diseases, including systemic lupus erythematosus (SLE). We performed a retrospective observational study of data provided by patients in the PLM SLE community to characterize demographics, clinical characteristics, patient experience, and symptom impact. METHODS: Adults who registered with PLM in 2011-2017 and reported SLE diagnosis and treatment with one or more SLE-related drug (antimalarials, immunosuppressives, corticosteroids, calcineurin inhibitors, or biologics) were included in the analysis. Information reported within 30 days from PLM registration was used to assess patient eligibility; demographics and clinical characteristics; and primary outcome measures of SLE treatments, symptoms, primary lupus manifestations, and comorbidities. RESULTS: Among 21,101 PLM members included in this analysis, median ages at registration, onset of SLE symptoms, and SLE diagnosis were 46 years (interquartile range [IQR] 38-53, n = 21,101), 30 years (IQR 21-39; n = 6489), and 36 years (IQR 27-44; n = 6936), respectively. Most patients were female (96.8%, n = 20,370). Country of residence was reported by 19,502 patients (92.4%), of whom 18,491 (94.8%) were US residents. Race was recorded by 17,994 patients (85.3%), of whom 67.8% were white and 22.4% were black/African American. Patients reported a mean of 2.2 SLE-related medications, including antimalarials (83.8%), corticosteroids (78.8%), immunosuppressives (32.3%), and biologics (9.4%). Fatigue, pain, and joint pain were rated as moderate or severe by at least 80% of patients who reported these symptoms. Reported primary lupus manifestations and comorbidities included fibromyalgia (7.9%), discoid lupus (6.8%), lupus nephritis (6.3%), rheumatoid arthritis (4.8%), subacute cutaneous lupus (4.7%), central nervous system lupus (3.9%), Sjögren's syndrome (3.9%), and lupus pneumonitis (3.1%). CONCLUSIONS: Age, sex, and race of patients in the PLM SLE community are broadly consistent with characteristics of the general SLE population in the United States. The PLM SLE population may provide valuable data on self-reported patient experience. Plain language summary available for this article.

Real world evidence (RWE) - a disruptive innovation or the quiet evolution of medical evidence generation?

Stakeholders in healthcare are increasingly turning to real world evidence (RWE) to inform their decisions, alongside evidence from randomized controlled trials. RWE is generated by analysing data gathered from routine clinical practice, and can be used across the product lifecycle, providing insights into areas including disease epidemiology, treatment effectiveness and safety, and health economic value and impact. Recently, the US Food and Drug Administration and the European Medicines Agency have stated their ambition for greater use of RWE to support applications for new indications, and are now consulting with their stakeholders to formalize standards and expected methods for generating RWE. Pharmaceutical companies are responding to the increasing demands for RWE by developing standards and processes for each stage of the evidence generation pathway. Some conventions are already in place for assuring quality, whereas other processes are specific to the research question and data sources available. As evidence generation increasingly becomes a core role of medical affairs divisions in large pharmaceutical companies, standards of rigour will continue to evolve and improve. Senior pharmaceutical leaders can drive this change by making RWE a core element of their corporate strategy, providing top-level direction on how their respective companies should approach RWE for maximum quality. Here, we describe the current and future areas of RWE application within the pharmaceutical industry, necessary access to data to generate RWE, and the challenges in communicating RWE. Supporting and building on viewpoints from industry and publicly funded research, our perspective is that at each stage of RWE generation, quality will be critical to the impact that RWE has on healthcare decision-makers; not only where RWE is an established and evolving tool, but also in new areas that have the potential to disrupt and to improve drug development pathways.

Scaling PatientsLikeMe via a "Generalized Platform" for Members with Chronic Illness: Web-Based Survey Study of Benefits Arising.

BACKGROUND: Launched in 2006 for patients with amyotrophic lateral sclerosis, PatientsLikeMe is an online community offering patient-reported outcomes, symptom tracking, and social features. Every member of the site can see all the data reported by every other member, view aggregated reports, identify "patients like them," and learn about treatment options in order to live better with their condition. In previous studies, members reported benefits such as improved condition knowledge, increased medication adherence, and better management of side effects. However, the site evolved in 2011 from condition-specific "vertical" communities consisting only of people with the same disease to a "generalized platform," in which every patient could connect with every other patient regardless of condition and with generic, rather than condition-specific, data tools. Some, but not all, communities received further custom tracking tools. OBJECTIVE: We aimed to understand (1) whether members of PatientsLikeMe using the generalized platform still reported similar benefits and (2) assess factors associated with benefits, such as community customization, site use, and patient activation. METHODS: A cross-sectional retrospective custom survey was fielded to 377,625 members between 2016 and 2017 including the Patient Activation Measure (PAM). A benefit index was developed for comparability across conditions. RESULTS: The invitation was viewed by 26,048 members of whom 11,915 did not respond, 5091 opted out, 1591 provided partial data, and 17 were screened out. Complete responses were received from 7434 participants. Users perceived greatest benefit in understanding how their condition may affect them (4530/6770, 66.91% participants, excluding "does not apply" answers), understanding what might help them live better with their condition (4247/6750, 62.92%), which treatments were available (4143/6898, 60.06%), understanding treatment side effects (4182/6902, 60.59%), and important factors in making treatment decisions (3919/6813, 57.52%). The benefit index was 29% higher for the "most activated" patients (PAM level 4 vs PAM level 1; relative risk [RR]=1.29, P<.001), 21% higher for conditions with some community customization versus none (RR=1.21, P<.001), and 11% higher in those using the site most often versus least (RR=1.11, P<.001). CONCLUSIONS: Members of the generalized platform reported a range of benefits related to improved knowledge and understanding of their condition and treatment management. Condition-specific customization may improve their experience still further. Future studies will explore longitudinal changes to patient activation.

Glycated Hemoglobin, Body Weight and Blood Pressure in Type 2 Diabetes Patients Initiating Dapagliflozin Treatment in Primary Care: A Retrospective Study.

INTRODUCTION: The present study aimed to describe characteristics of patients with type 2 diabetes (T2D) in UK primary care initiated on dapagliflozin, post-dapagliflozin changes in glycated hemoglobin (HbA1c), body weight and blood pressure, and reasons for adding dapagliflozin to insulin. METHODS: Retrospective study of patients with T2D in the Clinical Practice Research Datalink with first prescription for dapagliflozin. Patients were included in the study if they: (1) had a first prescription for dapagliflozin between November 2012 and September 2014; (2) had a Read code for T2D; (3) were registered with a practice for at least 6 months before starting dapagliflozin; and (4) remained registered for at least 3 months after initiation. A questionnaire ascertained reason(s) for adding dapagliflozin to insulin. RESULTS: Dapagliflozin was most often used as triple therapy (27.7%), dual therapy with metformin (25.1%) or added to insulin (19.2%). Median therapy duration was 329 days [95% confidence interval (CI) 302-361]. Poor glycemic control was the reason for dapagliflozin initiation for 93.1% of insulin-treated patients. Avoiding increases in weight/body mass index and insulin resistance were the commonest reasons for selecting dapagliflozin versus intensifying insulin. HbA1c declined by mean of 9.7 mmol/mol (95% CI 8.5-10.9) (0.89%) 14-90 days after starting dapagliflozin, 10.2 mmol/mol (95% CI 8.9-11.5) (0.93%) after 91-180 days and 12.6 mmol/mol (95% CI 11.0-14.3) (1.16%) beyond 180 days. Weight declined by mean of 2.6 kg (95% CI 2.3-2.9) after 14-90 days, 4.3 kg (95% CI 3.8-4.7) after 91-180 days and 4.6 kg (95% CI 4.0-5.2) beyond 180 days. In patients with measurements between 14 and 90 days after starting dapagliflozin, systolic and diastolic blood pressure decreased by means of 4.5 (95% CI -5.8 to -3.2) and 2.0 (95% CI -2.9 to -1.2) mmHg, respectively from baseline. Similar reductions in systolic and diastolic blood pressure were observed after 91-180 days and when follow-up extended beyond 180 days. Results were consistent across subgroups. CONCLUSION: HbA1c, body weight and blood pressure were reduced after initiation of dapagliflozin in patients with T2D in UK primary care and the changes were consistent with randomized clinical trials. FUNDING: AstraZeneca.

Using big data from health records from four countries to evaluate chronic disease outcomes: a study in 114 364 survivors of myocardial infarction.

AIMS: To assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. METHODS AND RESULTS: We used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002-11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04-1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21-1.96)]. CONCLUSION: The validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study.

Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population.

PURPOSE: The co-administration of cytochrome P450 3A4 (CYP3A4) inhibitors with simvastatin or atorvastatin (CYP3A4-metabolised statins) is associated with increased statin exposure and can increase the risk of adverse drug reactions. The aim of this study was to measure the concomitant exposure of patients to CYP3A4-metabolised statins and CYP3A4 inhibitors in the UK primary care population. METHODS: The co-administration of statins and CYP3A4 inhibitors during 2008 was examined in the General Practice Research Database, a large nationally representative UK primary care database. All known inhibitors were included with labelled inhibitors identified using the Medicines and Healthcare products Regulatory Agency Drug Safety Update and UK summary of product characteristics for statins. Exposure was examined in patients overall, patients 65 years and older and those prescribed higher doses of statins. RESULTS: There were 364,574 patients included in the analyses. Ninety-three percent of the patients were prescribed CYP3A4-metabolised statins, most whom received simvastatin (72%) and atorvastatin (24%). Approximately one third (30%) of the patients prescribed a CYP3A4-metabolised statin had also been prescribed a concomitant CYP3A4 inhibitor during the study period, including 11% prescribed a concomitant labelled inhibitor, with an annualised median days of concomitant use of 173 days, predominantly involving macrolide antibiotics and calcium channel blockers co-prescriptions. Rates were higher in the subgroup aged 65 and over and in those on high dose statins. CONCLUSIONS: The co-prescription of CYP3A4-metabolised statins and CYP3A4 inhibitors is common in UK primary care. This co-prescription suggests the limited appreciation of potential interactions and Medicines and Healthcare products Regulatory Agency safety advice, with the potential to increase likelihood for side effects amongst patients. Strategies to reduce drug interactions with potential adverse effects should be targeted at prescribers and pharmacists.

Clopidogrel discontinuation after acute coronary syndromes: frequency, predictors and associations with death and myocardial infarction--a hospital registry-primary care linked cohort (MINAP-GPRD).

AIMS: Adherence to evidence-based treatments and its consequences after acute myocardial infarction (MI) are poorly defined. We examined the extent to which clopidogrel treatment initiated in hospital is continued in primary care; the factors predictive of clopidogrel discontinuation and the hazard of death or recurrent MI. METHODS AND RESULTS: We linked the Myocardial Ischaemia National Audit Project registry and the General Practice Research Database to examine adherence to clopidogrel in primary care among patients discharged from hospital after MI (2003-2009). Hospital Episode Statistics and national mortality data were linked, documenting all-cause mortality and non-fatal MI. Of the 7543 linked patients, 4650 were prescribed clopidogrel in primary care within 3 months of discharge. The adjusted odds of still being prescribed clopidogrel at 12 months were similar following non-ST-elevation myocardial infarction (NSTEMI) 53% (95% CI, 51-55) and ST-elevation myocardial infarction (STEMI) 54% (95% CI, 52-56), but contrast with statins: NSTEMI 84% (95% CI, 82-85) and STEMI 89% (95% CI, 87-90). Discontinuation within 12 months was more frequent in older patients [>80 vs. 40-49 years, adjusted hazard ratio (HR) 1.50 (95% CI, 1.15-1.94)] and with bleeding events [HR 1.34 (95% CI, 1.03-1.73)]. 18.15 patients per 100 person-years (95% CI, 16.83-19.58) died or experienced non-fatal MI in the first year following discharge. In patients who discontinued clopidogrel within 12 months, the adjusted HR for death or non-fatal MI was 1.45 (95% CI, 1.22-1.73) compared with untreated patients, and 2.62 (95% CI, 2.17-3.17) compared with patients persisting with clopidogrel treatment. CONCLUSION: This is the first study to use linked registries to determine persistence of clopidogrel treatment after MI in primary care. It demonstrates that discontinuation is common and associated with adverse outcomes.

Annual cost of managing bipolar disorder to the UK healthcare system.

INTRODUCTION: Bipolar disorder is a common illness characterized by recurrent episodes of pathological disturbances of mood. The aim of this study was to estimate the annual cost associated with bipolar disorder to the UK healthcare system (National Health Service). METHODS: A retrospective observational study was conducted. Primary care resource use was estimated using the IMS Disease Analyzer, a nationally representative sample of general practitioner (GP) practices. Two sources of data from the NHS Information Centre were used to assess resource use in secondary care and in outpatient and community mental health. The number of bed days and day attendances for patients hospitalized was obtained from the Hospital Episode Statistics (HES). This was supplemented with Mental Health Minimum Dataset (MHMDS) to quantify outpatient and community mental health face-to-face contacts. Resource use was examined between 01 April 2007 and 31 March 2008. RESULTS: The annual NHS cost of bipolar disorder was estimated to be £ 342 million at 2009/2010 prices. Hospitalizations accounted for 60%, outpatient and community mental health 26.7%, and medication in primary care 7.4% of the overall direct costs of care. LIMITATIONS: This study may be confounded by the absence of a control group. This study was limited to an assessment of direct healthcare costs only, not the wider societal cost of bipolar disorder. CONCLUSIONS: The direct medical cost of managing bipolar disorder in the UK healthcare system is considerable. Therapeutic strategies that optimize community-based management, prevention of recurrence and hospitalization could reduce the economic burden of this illness.

Anticoagulation in patients with non-valvular atrial fibrillation: an evaluation of stability and early factors that predict longer-term stability on warfarin in a large UK population.

OBJECTIVE: To determine the proportion of patients with non-valvular atrial fibrillation (NVAF) treated with warfarin that achieved a 6-month period within the target INR range (stability). To then evaluate any associations between stability and outcome and to determine whether stability can be predicted by clinical factors at an early stage in warfarin treatment. METHODS: This study was a record linkage study in 1513 patients with NVAF treated with warfarin for a minimum of 6-months, carried out in a large UK population. The main outcome measures were stability (defined as six months within the target INR range [2.0-3.0]), thromboembolic and bleeding event rates and mortality. Secondary outcome measures were the predictive value of baseline characteristics and other treatment variables. RESULTS: Stability was achieved in 52% of the study group. Standardised mean survival was significantly higher in the group who achieved stability (Delta = 16.91 months, p < 0.001) with a hazard ratio of 4.36 (p < 0.001). The stable group had a lower rate of both thromboembolic events (0.8% vs. 2.3% per patient year) and bleeds recorded on inpatient diagnoses (0.4% vs. 1.2% per patient year). Failure to achieve stable control was associated with age (Odds Ratio [OR] 1.011 (95% Confidence Interval [CI] 1.001-1.021)) and morbidity at baseline (OR 1.015; 95% CI 1.007-1.022). An increase in mean time between visits (OR 0.939; 95% CI 0.926-0.952) and the percentage time in range (OR 0.889; 95% CI 0.879-0.900) was associated with a decrease in the chance of instability. Greater variability in INR was also associated with a failure to achieve stability (OR 1.518; 95% CI 1.427-1.615). Receiver Operator Characteristic (ROC) analysis using data from the first three months of treatment demonstrated good discrimination of stability using age and morbidity at baseline and percentage time in range and frequency of visits during the first three months of treatment (area under curve [AUC] 0.780; standard error [SE] 0.012; 95% CI 0.757-0.803). CONCLUSIONS: Many patients never achieved a period of 6-months stability and were at increased risk of thromboembolic events and bleeds. Age, morbidity at baseline and variability of INR control in the first three months could be used to predict instability using warfarin. This study infers that patients should be treated more intensively in the early stages of warfarinisation in order to improve outcome.

Systematic review comparing meropenem with imipenem plus cilastatin in the treatment of severe infections.

OBJECTIVE: To compare the effectiveness of meropenem with imipenem plus cilastatin in the treatment of severe infections. DATA SOURCES: CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in March 2004. No restriction was placed on language. STUDY SELECTION: Randomized controlled trials of adult patients with severe infections treated with meropenem or imipenem plus cilastatin at an equal dose, on a gram-for-gram basis, and with the same dosing regimen. DATA EXTRACTION: Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality with differences in opinion adjudicated by a third party. Data were extracted on clinical response, bacteriologic response, mortality and adverse events. DATA SYNTHESIS: A total of 27 trials met the inclusion criteria. Meta-analyses were carried out using a Fixed Effects model. Results demonstrated that when compared to imipenem plus cilastatin, meropenem is associated with a significantly greater clinical response (Relative Risk 1.04; 95% Confidence Interval: 1.01-1.06), a significantly greater bacteriologic response (RR 1.05; 95% CI: 1.01-1.08), a non-significant reduction in mortality (RR 0.98; 95% CI: 0.71-1.35), and a significantly lower adverse event rate (RR 0.87; 95% CI: 0.77-0.97). CONCLUSIONS: This systematic review demonstrates that meropenem compared to imipenem plus cilastatin has a significantly greater clinical and bacteriologic response with a significant reduction in adverse events. There was no evidence of heterogeneity or publication bias and the analyses were robust to changes in the inclusion/exclusion criteria and use of a Random Effects model.