Lapatinib plus capecitabine versus capecitabine alone for HER2+ (ErbB2+) metastatic breast cancer: quality-of-life assessment.

The randomized phase III trial EGF100151 demonstrated that the combination of lapatinib plus capecitabine (L + C) significantly improved time to progression (TTP) compared with capecitabine alone (C) in heavily pretreated patients with HER2+ (ErbB2+) advanced or metastatic breast cancer. This analysis assessed the effects of study treatments on quality of life (QOL) among patients in EGF100151. Quality of life was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and EuroQoL (EQ-5D) questionnaires. Patients completed questionnaires during efficacy and safety assessment visits (i.e., at screening visit, every 6 weeks for the first 24 weeks, every 12 weeks thereafter, and at discontinuation of study treatment). Primary analyses compared the treatment groups based on change from baseline QOL. Exploratory analyses compared proportion of patients achieving minimum important differences (MID) in QOL scores and the relationship between QOL and tumor status. Quality of life for patients in both treatment groups was maintained during 24 weeks of follow-up. Adjusted mean changes from baseline in all QOL scores for the L + C arm were comparable to those for the C arm. The between-group differences ranged from 0.7 to 2.2 (FACT-B total) and 0.3 to 1.8 (EQ-5D visual analog scale) and were consistently in favor of the L + C arm, although not statistically significant. Patients with an objective tumor response or stable disease showed clinically meaningful differences in QOL scores compared to patients with progressive disease. A greater proportion of patients receiving L + C versus C achieved the MID for all five QOL scores, although differences were not statistically significant. The addition of lapatinib to capecitabine significantly increases TTP without any evidence of a deleterious effect on patients' QOL, confirming its clinical benefit in this heavily pretreated patient population with advanced HER2+ breast cancer that has progressed on trastuzumab therapy.

Health state utility scores in advanced non-small cell lung cancer.

BACKGROUND: The aim of the study was to capture societal utility scores for health state descriptions of advanced, metastatic non-small cell lung cancer (NSCLC), as well as determine disutility associated with specific disease symptoms. METHODS: NSCLC health states were produced based on an adaptation of existing health state descriptions for metastatic lung cancer. The health states were expanded to contrast disease state (responding disease and stable disease) and impact of specific severe symptoms (cough; dyspnoea; pain; or no additional severe symptoms). Interviews with five lung cancer clinicians were carried out to assess the content and face validity of the existing health states as descriptions specific to NSCLC. The interviews also sought to explore the impact of the disease symptoms of interest. The resulting health states were reviewed by two psychometric experts independently. The final health states were piloted in a conventional standard gamble interview which revealed no significant issues in interpretation or comprehension. In the main study, 101 members of the general public assessed their preference for each health state in a chained standard gamble (SG) interview and on a visual analogue scale (VAS) rating scale. All participants also completed the EQ-5D and a socio-demographic form. RESULTS: The study sample was a relatively good match to the characteristics of the general public in England and Wales. A mixed model analysis revealed that age, gender, and HRQL were not significant predictors of utility, but a treatment response and each of the disease symptoms were. When adjusted to match census data, stable disease with no additional symptoms had a utility value of 0.626. Health state values declined by 0.069 with the addition of pain; 0.050 for dyspnoea; or 0.046 for cough. A treatment response would result in a utility gain of 0.086. CONCLUSIONS: Members of the general public showed a preference for responding disease over stable disease and a stable health state with no additional symptoms over a stable health state with one of the three common NSCLC symptoms: cough, dyspnoea, and pain. The study highlights the value that society places on the avoidance of severe symptoms that some people with NSCLC can experience.

The effect of dosing frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women: a comparison of studies in the United States, the United Kingdom, and France.

OBJECTIVES: The aim of this study was to determine the effect of dose frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women and to compare findings from 3 different health care systems. METHODS: Three independently performed retrospective cohort analyses were performed using observational data sources. In the United States, bisphosphonate-naive postmenopausal women were identified from a database providing information on health plan prescription drug claims; in the United Kingdom and France, bisphosphonate-naive postmenopausal women were identified from a database of medical records supplied by general practice physicians. The women were grouped into 2 cohorts: those who were initiated on a weekly regimen of alendronate 70 mg or risedronate 35 mg and those initiated on a daily regimen of alendronate 5 or 10 mg or risedronate 5 mg. Compliance was measured in terms of the medication possession ratio (MPR), which was defined as the proportion of days in the 12-month follow-up period for which patients were covered by prescriptions for bisphosphonates. Persistence was measured as the number of days from the date of the index prescription to the last day of prescription coverage within the followup period. Women were classified as nonpersistent if the gap between prescriptions was > 30 days. RESULTS: The study included 2741 postmenopausal women with osteoporosis from the United States, 7567 from the United Kingdom, and 5332 from France. The mean (SD) age of the women was 73.0, 71.7, and 69.7 years in the 3 countries, respectively. The overall MPR was 61% in the United States, 74% in the United Kingdom, and 58% in France. In all 3 countries, women on a weekly regimen had a significantly greater MPR than women on a daily regimen (69% vs 58%, respectively, in the United States; 76% vs 64% in the United Kingdom; and 59% vs 53% in France; all, P < 0.001). Women on a weekly regimen of bisphosphonates persisted with treatment significantly longer than women on a daily regimen (227 vs 185 days, respectively, in the United States; 249 vs 208 in the United Kingdom; and 179 vs 155 in France; all, P < 0.001). A significantly greater proportion of the women on a weekly regimen persisted with treatment for 12 months compared with those on a daily regimen (44% vs 32%, respectively, in the United States; 52% vs 40% in the United Kingdom; and 51% vs 44% in France; all, P < 0.001). CONCLUSIONS: In all 3 countries, postmenopausal women prescribed a weekly regimen of bisphosphonates had significantly greater rates of compliance than women prescribed a daily regimen, and they persisted longer with treatment. However, compliance and persistence rates were suboptimal for both regimens.

The impact of dosing frequency on compliance and persistence with bisphosphonates among postmenopausal women in the UK: evidence from three databases.

BACKGROUND: Bisphosphonates are currently among the most effective therapies for the treatment of osteoporosis and provide one of the mainstays of treatment in the UK. However studies in several countries have all reported sub-optimal compliance and persistence with treatment. OBJECTIVE: To examine the impact of dosing frequency on compliance and persistence with bisphosphonates in the UK. METHODS: Three UK General Practitioner sourced databases, the General Practice Research Database (GPRD), IMS Disease Analyzer (MEDIPLUS) and the Doctors Independent Network Database (DIN-LINK) were used to identify bisphosphonate naïve postmenopausal women. In each of the three retrospective analyses women were grouped into weekly or daily cohorts and followed for 12 months from an initial prescription. Compliance was measured as a Medication Possession Ratio (MPR), defined as the proportion of days for which patients had prescription coverage. Persistence was measured as the number of continuous days of treatment from the initial prescription to the end of the last prescription issued in the follow-up period. RESULTS: GPRD, MEDIPLUS and DIN-LINK provided access to 7567, 5962 and 1801 women, respectively. All three analyses consistently demonstrated that those on weekly regimens had a higher MPR than those on daily regimens (GPRD 76.2%, CI(95%,) 75.4-77.0 vs. 63.5%, CI(95%) 61.2-65.8, MEDIPLUS 70.3%, CI(95%) 69.3-71.2 vs. 56.3%, CI(95%) 53.8-58.9, DIN-LINK 59.5%, CI(95%) 59.4-59.6 vs. 46.3%, CI(95%) 45.9-46.7) (p < 0.0001) and persisted longer with treatment (GPRD 249, CI(95%) 246-253 vs. 208, CI(95%) 199-217, MEDIPLUS 228, CI(95%) 224-231 vs. 186, CI(95%,) 176-196, DIN-LINK 235, CI(95%) 234-236 vs. 189, CI(95%) 187-191) days respectively), (p < 0.0001). CONCLUSIONS: Although this study only provided an indirect measure of medication usage, it demonstrated that a less frequent dosing regimen significantly improved levels of both compliance and persistence; however, even on weekly regimens bisphosphonate usage remains sub-optimal thereby reducing the clinical benefits.

Incorporating carer effects into economic evaluation.

BACKGROUND: Despite great interest in the development of methods used in the economic evaluation of health technologies, the effects of carer costs and quality of life (QOL) on the cost effectiveness of treatments has not been widely explored. Yet carer effects are clearly evident in the literature and relevant to the perspective of many published economic evaluations. OBJECTIVE: To examine whether patient QOL is associated with carer time and carer QOL. METHODS: We used two datasets to investigate carer effects. Firstly, we used 40,312 cases from the Health Outcomes Data Repository (HODaR) to assess the relationship between patient utility, using the EuroQoL (EQ)-5D, and the number of days care needed from friends and relatives. The stability of the relationship across patient subgroups was assessed by replicating the analysis in ten disease groups. Secondly, we used 64 cases from a study of patients with Alzheimer's disease and their primary carer. These data allowed us to estimate the relationships between patient and carer utility, using the EQ-5D, and patient utility and carer burden using the Community Dementia Quality of Life Profile (CDQLP). RESULTS: For carer time, a linear model showed that each 0.1-point reduction in patient utility was associated with a 2.5-day increase in carer time over a 6-week period. A more general model, based on EQ-5D domain scores, was better specified and showed that decreased functioning within each domain is associated with increased carer time. Problems with self-care and usual activities have the greatest impact on carer time. These models do not appear to be stable across different disease groups. For carer utility, the relationships between carer and patient utility have low explanatory power and are poorly specified. A clearer relationship is shown between carer burden and utility, such that when sociodemographic covariates are introduced, the relationship reaches conventional levels of statistical significance (p < 0.05). CONCLUSIONS: The preliminary work described here shows that improving patient QOL may reduce the need for carer time and improve carer QOL. Incorporating such effects into economic evaluations will change cost-per-QALY estimates, with the size of reduction dependent on the domains of health affected by treatment. Clinical studies need to capture carer data so that we can better understand these effects, and how they impact on economic evaluation.

The effects of orlistat in patients with diabetes: improvement in glycaemic control and weight loss.

OBJECTIVE: In addition to direct weight reduction, there may be other benefits of obesity treatment including improved insulin sensitivity. The purpose of this study was to characterise concomitant diabetes drug use and the related costs in patients with diabetes treated with orlistat (Xenical) in the first 6 months of treatment. METHODS: One hundred overweight patients with diabetes and a body mass index (BMI) > or = 28 kg/m2 were enrolled in a structured UK hospital-based weight management clinic and treated with orlistat plus behavioural interventions. Among other measures, weight, glucose control (HbA1c) and drug treatment were recorded. Subjects were followed-up for a maximum of 24 months at intervals of 1-3 months, with a maximum treatment period of 24 months. RESULTS: The majority of subjects (91%) had type 2 diabetes. They had a mean age of 55 years and 55% were women. For patients followed up at 6 months, their mean BMI at baseline was 39.5 kg/m2 with a mean HbA1c of 7.6%. The mean weight loss at 6 months was 7.1 kg (p < 0.001). Despite a significant average absolute HbA1c reduction of 0.62% (p < 0.001), the most notable gains were made by those with the highest baseline HbA1c values (a mean relative reduction of 20% for those above the 75th percentile). There were 50 patients treated with insulin at baseline and 47 at 6 months. Of those treated with insulin, the mean dose was 130 units at baseline and 90 units at 6 months (p < 0.001). Twenty patients (44.4%) initially treated with oral hypoglycaemic agents alone reduced their dose after 6 months (not significant). Despite marked improvement in insulin sensitivity (baseline mean, 1.24 units/kg; 6 month mean, 0.90 units/kg [p < 0.001]) there was no correlation with BMI change. The average cost of diabetes treatment at baseline was pound 1.16 per day and pound 0.83 at 6 months (p < 0.001). Age was the only independent predictor for insulin dose reduction. CONCLUSIONS: Orlistat appears to reduce the need for concomitant diabetes medication irrespective of weight loss, a reduction that is likely to represent a large cost offset for orlistat treatment.

Cost-effectiveness of lapatinib plus capecitabine in women with HER2+ metastatic breast cancer who have received prior therapy with trastuzumab.

BACKGROUND: In a phase III trial of women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab, an anthracycline, and taxanes (EGF100151), lapatinib plus capecitabine (L+C) improved time to progression (TTP) versus capecitabine monotherapy (C-only). In a trial including HER2+ MBC patients who had received at least one prior course of trastuzumab and no more than one prior course of palliative chemotherapy (GBG 26/BIG 03-05), continued trastuzumab plus capecitabine (T+C) also improved TTP. METHODS: An economic model using patient-level data from EGF100151 and published results of GBG 26/BIG 03-05 as well as other literature were used to evaluate the incremental cost per quality-adjusted life-year [QALY] gained with L+C versus C-only and versus T+C in women with HER2+ MBC previously treated with trastuzumab from the UK National Health Service (NHS) perspective. RESULTS: Expected costs were £28,816 with L+C, £13,985 with C-only and £28,924 with T+C. Corresponding QALYs were 0.927, 0.737 and 0.896. In the base case, L+C was estimated to provide more QALYs at a lower cost compared with T+C; cost per QALY gained was £77,993 with L+C versus C-only. In pairwise probabilistic sensitivity analyses, the probability that L+C is preferred to C-only was 0.03 given a threshold of £30,000. The probability that L+C is preferred to T+C was 0.54 regardless of the threshold. CONCLUSIONS: When compared against capecitabine alone, the addition of lapatinib has a cost-effectiveness ratio exceeding the threshold normally used by NICE. Compared with T+C, L+C is dominant in the base case and approximately equally likely to be cost-effective in probabilistic sensitivity analyses over a wide range of threshold values.

An audit to determine the time taken to administer intravenous bisphosphonate infusions in patients diagnosed with metastatic breast cancer to bone in a hospital setting.

OBJECTIVE: Bone metastases can occur in many forms of cancer. More than two-thirds of women with metastatic breast cancer may be affected by bone metastasis during the course of their disease. Bisphosphonates, which inhibit osteoclast-mediated bone resorption, are an established standard of care for patients with bone metastases. For patients with cancer and bone metastases, bisphosphonates are associated with a significant reduction in skeletal-related events such as vertebral fractures, non-vertebral fractures as well as increasing the time to skeletal event. The purpose of this study was to quantify the current time involved in the administration of i.v. bisphosphonates and how this might impact on patient experience and cancer unit capacity. RESEARCH DESIGN AND METHODS: A pilot audit was initially conducted at the Royal Marsden Hospital (RMH), London (both Chelsea and Sutton sites), and was followed by audits at a further two UK hospital sites: Velindre Hospital, Cardiff and the Royal Surrey County Hospital, Guildford. The study was conducted between December 2005 and September 2006. RESULTS: Overall, 151 forms were completed. Of the total patients audited, approximately 71% had a diagnosis of breast cancer. Where data on the reason for attendance were collected (Velindre and the Royal Surrey County Hospital), over 77% of patients attended hospital for the sole reason of having an i.v. bisphosphonate administered. The majority of patients (94%) required cannulation prior to infusion and, at the sites where this information was recorded (Royal Surrey County Hospital and Velindre Hospital), almost one-third of patients required two or more attempts before they were successfully cannulated. The time that the patients spent on the unit where the i.v. bisphosphonates were administered was greater for patients receiving pamidronate compared to those receiving zoledronic acid (2 h 36 min and 1 h 38 min, respectively). The magnitude of the difference was not as great as would be expected considering zoledronic acid should take one-sixth of the time to administer (Royal Marsden Hospital, pamidronate 1 h 29 min, zoledronic acid 18 min: Royal Surrey County Hospital, zoledronic acid 21 min: Velindre Hospital, pamidronate 1 h 42 min, zoledronic acid 17 min). CONCLUSIONS: I.v. bisphosphonates are accepted as standard clinical practice for the management of metastatic bone disease. They are often prescribed for long periods of time, so tolerability and patient acceptability are important factors in therapy. The administration of i.v. bisphosphonates contributes a substantial time burden for patients travelling to the hospital, considering that in most cases the purpose is for this treatment only. It also places a significant burden on hospital resources, creating capacity planning challenges. Receiving an i.v. bisphosphonate also has other disadvantages associated with it, such as the need for patients to undergo repeated cannulation. Service redesign, such as home administration of i.v. bisphosphonates, could help to overcome issues highlighted in this audit. The use of oral alternatives to pamidronate and zoledronic acid which may be more convenient for patients, and perhaps also cost-effective, should also be of ongoing interest.

Assessing the total costs of blood delivery to hospital oncology and haematology patients.

OBJECTIVE: To determine direct costs associated with a blood transfusion session in two hospital settings. RESEARCH DESIGN AND METHODS: The study was conducted in two United Kingdom hospital sites during April 2004. Transfusion sessions for patients receiving units of red blood cells within either haematology or oncology departments were followed using time and motion techniques to measure the direct costs. Other data were collected from the centres to calculate the cost of disposables, blood wastage and blood bank machines. RESULTS: Total mean staff cost per transfusion of 2 units was 37.24 pounds sterling (9.68 pounds sterling for blood bank and 27.56 pounds sterling for ward procedures). The mean cost of disposables was 13.25 pounds sterling and the mean cost for blood products was 287.56 pounds sterling. The mean cost of wastage was 11.86 pounds sterling per transfusion. After including other derived costs, such as hospital stay, the mean cost for a transfusion of 2 units of blood was estimated to be 546.12 pounds sterling. CONCLUSION: This study estimates the cost of an average blood transfusion of 2 units to be 546.12 pounds sterling. It should be noted that significant indirect costs, such as those incurred by patients, their carers and societal costs, have not been considered. Against the background of finite blood resources and other factors such as patient quality of life, blood transfusion may not represent the best choice for patient care. Alternative treatments should be considered.

The validity of searching routinely collected general practice computer data to identify patients with chronic kidney disease (CKD): a manual review of 500 medical records.

BACKGROUND: We conducted a search of 12 practices' routinely collected computer data in three localities across the UK and found that 4.9% of the registered population had an estimated glomerular filtration rate (GFR) of <60 ml/min/1.73 m(2) (equivalent to stages 3-5 CKD). Only 3.6% of these were known to have renal disease. Although UK general practice is computerized, important clinical data might be recorded in letters or free-text computer entries and might therefore be invisible to the standard computer search tools. We therefore manually searched through all the records of patients with stages 3-5 CKD in one practice, to test the validity of the computer generated diagnosis and to see if other relevant information was missed by the computer search. METHODS: We identified 492 people with stages 3-5 CKD using computer searching and then manually searched their computer records and written notes for any missed data. The dataset included cardiovascular morbidities and risk factors including diabetes; drugs which may impair renal function; known renal disease; and terminal diagnoses and dementia. RESULTS: The manual searches only added four renal diagnoses to the 36 already identified. Although heart failure and stroke appear to be over-estimated by computer searches, other cardiovascular diagnoses were reliably recorded. Cardiovascular risk factors and drug recording is a strength of general practice computer data. It is complete and contemporary, though most patients had scope to have their cardiovascular risk reduced further. Eighty-four percent had a haemoglobin estimation, and a higher proportion with reduced renal function were anaemic (P<0.001). Testing for proteinuria was less well recorded; negative stick tests were not recorded. Clinical diagnoses of prostatism and bladder outflow problems made these data hard to interpret. CONCLUSIONS: Automated searching of general practice computer records could provide a reliable and valid way of identifying people with stages 3-5 CKD who could benefit from interventions readily available in primary care.

Identifying patients with chronic kidney disease from general practice computer records.

BACKGROUND: Chronic kidney disease (CKD) is an important predictor of end-stage renal disease, as well as a marker of increased mortality. The New Opportunities for Early Renal Intervention by Computerised Assessment (NEOERICA) project aimed to assess whether people with undiagnosed CKD who might benefit from early intervention could be identified from GP computer records. METHODS: The simplified Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (GFR) and determine stage of CKD in patients from 12 practices in Surrey, Kent and Greater Manchester with SCr recorded in their notes. Further data were extracted on associated co-morbidities and potentially modifiable risk factors. RESULTS: One quarter (25.7%; 28,862/112,215) had an SCr recorded and one in five (18.9%) of them had a GFR <60 ml/min/1.73 m2 (equivalent to Stage 3-5 CKD), representing 4.9% of the population. Only 3.6% of these were recorded as having renal disease. Three-quarters (74.6%; 4075/5449) of those with Stage 3-5 CKD had one or more circulatory diseases; 346 were prescribed potentially nephrotoxic drugs and over 4000 prescriptions were issued for drugs recommended to be used with caution in renal impairment. CONCLUSIONS: Patients with CKD can be identified by searching GP computer databases; along with associated co-morbidities and treatment. Results revealed a similar rate of Stage 3-5 CKD to that found previously in the USA. The very low rate of recording of renal disease in patients found to have CKD indicates scope for improving detection and early intervention.