Management of EGFR Inhibitor-induced Skin Toxicity and Factors Impacting Patients' Adherence to Skin Toxicity Treatment: Health Care Provider and Patient Surveys in European Oncology Centers.

INTRODUCTION: This study aimed to provide a description of existing measures for the prevention and management of epidermal growth factor receptor inhibitor monoclonal antibody-induced skin toxicities and factors impacting patients' adherence to those measures in France, Germany, and Spain. MATERIALS AND METHODS: The study consisted of 2 separate surveys. Health care professionals (HCPs; oncologists and nurses) in France, Germany, and Spain were interviewed, and patients with metastatic colorectal cancer and head-and-neck cancer in France and Germany self-completed questionnaires. The study was conducted between February and July 2018. RESULTS: A total of 53 oncologists, 44 nurses, and 143 patients participated in the study. HCPs stated that skin toxicities moderately (52%) or severely (28%) impacted patient care. Ninety percent of HCPs reported routine provision of prophylactic measures. The great majority of patients self-reported adherence with the prophylactic (80% to 88% depending on the type of measures) and reactive (93% to drug prescription) skin toxicity recommendations. HCPs estimated patient adherence to be 45% for full adherence and 40% for partial adherence. Most HCPs reported a positive or very positive impact of preventive measures and recommendations on skin toxicity incidence and severity, patients' quality of life, and various aspects of quality of anti-cancer treatment. CONCLUSIONS: Skin toxicities are an important adversity negatively impacting on patient care. However, despite the positive perception of the effectiveness of skin toxicity prophylaxis, almost one-third of oncology centers did not provide formal guidelines, and 10% of HCPs did not provide routine prophylactic measures. Patient adherence appears to be high for epidermal growth factor receptor inhibitor monoclonal antibody-induced skin toxicity prevention measures.

Differing impact of clinical factors on the risk of fracture in younger and older women in the general population and an osteoporosis clinic population.

This study assesses the impact of risk factors for fracture in women aged 80+ and 60-79. The results suggest that risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort. PURPOSE: This study assesses whether the impact of classical risk factors for fracture due to osteoporosis is different in women aged 80+ and women aged 60-79. Since most prior research on the contribution of risk factors is based on patients below 80 years of age, this study aims to fill this knowledge gap to increase the accuracy of risk assessment in the oldest old. METHODS: Retrospective, observational cohort study using Swedish national health register data and BMD data from osteoporosis clinics. Women aged at least 60 were identified from a random sample of the general population and from the BMD databases and allocated to two populations representing patients at different stages of risk assessment. The relative impact of risk factors on fracture risk was assessed using multivariate competing risk regression with fracture as outcome and death as competing event. RESULTS: A total of 163,329 women were included from the general population (52,499 aged 80+) and 22,378 from the BMD databases (4563 aged 80+). The clinical risk factors with relatively highest effect on fracture risk in the older patients were prior fracture and hip T-score below - 2.5 SD. Other included risk factors showed lower impact in the older compared to the younger strata. CONCLUSIONS: This study confirms our understanding of the key risk factors for fracture: age, prior fracture, and a low T-score. Regarding remaining risk factors, risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort.

Risk of acute liver injury associated with use of antibiotics. Comparative cohort and nested case-control studies using two primary care databases in Europe.

PURPOSE: To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use. METHODS: The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year. Cases with ALI were identified within this cohort and classified as definite or probable, based on recorded medical information. The relative risk (RR) of ALI associated with antibiotic use was computed using Poisson regression. For the nested case-control analyses, up to five controls were matched to each case by age, sex, date and practice (in CPRD) and odds ratios (OR) were computed with conditional logistic regression. RESULTS: The age, sex and year adjusted RRs of definite ALI in the current antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI: 3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style, comorbidities and use of medications, the OR of ALI for current users of antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37) in BIFAP. CONCLUSION: Guided by a common protocol, both cohort and case-control study designs found an increased risk of ALI associated with the use of antibiotics in both databases, independent of the exposure and case definitions used. However, the magnitude of the risk was higher in CPRD compared to BIFAP.

The risk of acute liver injury among users of antibiotic medications: a comparison of case-only studies.

PURPOSE: The aims of this study were two-fold: (i) to investigate the effect of exposure to antibiotic agents on the risk of acute liver injury using a self-controlled case series and case-crossover study and (ii) to compare the results between the case-only studies. METHODS: For the self-controlled case series study relative incidence ratios (IRR) were calculated by dividing the rate of acute liver injury experienced during patients' periods of exposure to antibiotics to patients' rate of events during non-exposed time using conditional Poisson regression. For the case-crossover analysis we calculated Odds Ratios (OR) using conditional logistic regression by comparing exposure during 14- and 30-day risk windows with exposure during control moments. RESULTS: Using the self-controlled case series approach, the IRR was highest during the first 7 days after receipt of a prescription (10.01, 95% CI 6.59-15.18). Omitting post-exposure washout periods lowered the IRR to 7.2. The highest estimate in the case-crossover analysis was found when two 30-day control periods 1 year prior to the 30-day ALI risk period were retained in the analysis: OR = 6.5 (95% CI, 3.95-10.71). The lowest estimate was found when exposure in the 14-day risk period was compared to exposure in four consecutive 14-day control periods immediately prior to the risk period (OR = 3.05, 95% CI, 2.06-4.53). CONCLUSION: An increased relative risk of acute liver injury was consistently observed using both self-controlled case series and case-crossover designs. Case-only designs can be used as a viable alternative study design to study the risk of acute liver injury, albeit with some limitations.

The impact of persistence with bisphosphonates on health resource utilization and fracture risk in the UK: a study of patient records from the UK Clinical Practice Research Datalink.

RATIONALE, AIMS AND OBJECTIVES: Clinical trial data suggest that patients who have received bisphosphonates continue to benefit from them after discontinuation. However, data from real-world clinical practice are inconclusive. We assessed the impact of persistence and discontinuation on health resource utilization (HRU) and fracture rate in women who were prescribed oral bisphosphonates. METHOD: The study used data from the UK Clinical Practice Research Datalink. Women aged 50 years or older with a first prescription of oral bisphosphonate therapy between January 2000 and December 2007 were included. Multivariate modelling compared rate ratios for fracture and HRU between patients who had discontinued medication (shorter persistence group) and patients who took their medication for longer (longer persistence group). The interactions of elapsed time (measured as 6-month intervals) with HRU and with fracture rate for all patients within paired groups were also assessed. RESULTS: Overall, 36 320 patients were included. Pairwise comparisons showed that HRU and fracture rates were lower in longer persistence groups than in shorter persistence groups. Analysis by 6-month interval showed that, across all patients in persistence group pairs, HRU significantly increased for each additional 6 months elapsed; trends towards increased risk of fracture were also seen. CONCLUSION: In contrast to results from clinical trials, in this patient population the protective effect of oral bisphosphonates after discontinuation was not sufficient to reduce HRU and fracture rates to the levels that would be seen if patients had continued on therapy. Reducing the rate of treatment discontinuation may decrease the burden that osteoporosis places on both patients and health care systems.

Switch patterns of osteoporosis medication and its impact on persistence among postmenopausal women in the U.K. General Practice Research Database.

OBJECTIVE: This study aims to describe the switch patterns of osteoporosis medication in postmenopausal women and to explore the impact of switching on persistence. METHODS: This study used a cohort of postmenopausal women who initiated the first treatment with osteoporosis medication between 1995 and 2008. Selected women had switched at least once to a different frequency or type of osteoporosis medication during follow-up. For each study woman, we identified the first therapy (initial osteoporosis medication), second therapy (medication received at first switch), and, where available, third therapy (medication received at second switch), regardless of how many times she switched during follow-up. Persistence was defined as the number of days from the index date to the end of the last prescription within each episode of use. The Kaplan-Meier method was used to calculate persistence rates at 6 months, 1 year, 3 years, and 5 years. RESULTS: Of 20,638 women who switched osteoporosis treatment at least once in the study period, approximately 67% switched once, 21% switched twice, and 12% switched three times or more. Persistence rates for the second therapy were highest (% [95% CI], 46.6 [46.1-47.1], 35.0 [34.5-35.5], 18.8 [18.3-19.3], and 11.4 [10.9-11.7] at 6 mo, 1 y, 3 y, and 5 y, respectively), whereas persistence rates for the first therapy were lowest (% [95% CI], 34.3 [33.9-34.8], 21.6 [21.2-21.9], 5.90 [5.68-6.13], and 1.57 [1.45-1.69], respectively). CONCLUSIONS: Among women who switch their initial medication, even though switching to the second medication improves persistence during the initial therapy, persistence on the second and subsequent therapies remains suboptimal.

Opportunities for minimization of confounding in observational research.

Observational epidemiological studies are increasingly used in pharmaceutical research to evaluate the safety and effectiveness of medicines. Such studies can complement findings from randomized clinical trials by involving larger and more generalizable patient populations by accruing greater durations of follow-up and by representing what happens more typically in the clinical setting. However, the interpretation of exposure effects in observational studies is almost always complicated by non-random exposure allocation, which can result in confounding and potentially lead to misleading conclusions. Confounding occurs when an extraneous factor, related to both the exposure and the outcome of interest, partly or entirely explains the relationship observed between the study exposure and the outcome. Although randomization can eliminate confounding by distributing all such extraneous factors equally across the levels of a given exposure, methods for dealing with confounding in observational studies include a careful choice of study design and the possible use of advanced analytical methods. The aim of this paper is to introduce some of the approaches that can be used to help minimize the impact of confounding in observational research to the reader working in the pharmaceutical industry.

The incidence of idiopathic thrombocytopenic purpura among adults: a population-based study and literature review.

Published data on the epidemiology of idiopathic thrombocytopenic purpura (ITP) among adults are very limited. We conducted a study of ITP incidence using the General Practice Research Database in the United Kingdom. From 1992 to 2005, there were 840 cases of ITP among adults considering 21 749 623 person-years (PYs) of follow-up, for a crude incidence of 3.9 per 100 000 PYs [95% confidence interval (CI): 3.6, 4.1]. The incidence was higher among women [4.5 per 100 000 PYs (95% CI: 4.2, 4.9)] than men [3.2 per 100 000 PYs (95% CI: 2.8, 3.5)]. Among both women and men, incidence was higher at older ages and in later study years. In a systematic review of previously published literature, incidence of ITP among adults ranged from 1.6 to 2.68 per 100 000 persons per year; prevalence ranged from 9.5 to 23.6 per 100 000 persons. In order to improve the understanding of the disease burden of ITP, future studies should include a clearly defined definition of ITP and focus on well-described source populations that are geographically and ethnically diverse.

Risk of cataract among idiopathic thrombocytopenic purpura patients in the UK general practice research database.

PURPOSE: To estimate the incidence of cataracts in an adult idiopathic thrombocytopenic purpura (ITP) and in a comparable non-ITP population, stratified by age, gender and medication use in order to determine whether the risk of cataracts is greater in ITP patients. METHODS: Retrospective cohort of 745 newly diagnosed ITP patients and 3725 non-ITP subjects who were 18 years of age or older. The study population included patients registered on the General Practice Research Database (GPRD) during the period 1992-2005. ITP patients, identified using Read/Oxmis codes, were matched to five non-ITP patients. The exposure of interest was oral systemic steroid use and the primary outcome was cataracts. RESULTS: The overall incidence rate of cataracts in males was 11.8 per 1000 PY (95%CI: 6.3-20.2) and in females 9.0 per 1000 PY (95%CI: 5.2-14.4). In the non-ITP population these rates were 14.0 per 1000 PY (95%CI: 11.0-17.4) and 8.1 per 1000 PY (95%CI: 6.4-10.1), respectively. In the ITP population, users of oral steroids (OS) had a cataract incidence rate of 14.0 per 1000 PY (95%CI: 8.7-21.4) and non-users 6.0 per 1000 PY (95%CI: 2.8-11.4). In the non-ITP population, these rates were 16.9 per 1000 PY (95%CI: 11.9-23.3) and 9.2 per 1000 PY (95%CI: 7.6-11.0), respectively. OS were associated with an increased risk for cataracts. CONCLUSIONS: The rates of cataract in an adult ITP population are comparable to that in a non-ITP population.