Cost-effectiveness of palbociclib in hormone receptor-positive advanced breast cancer.

BACKGROUND: Palbociclib (PAL), a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6 for the treatment of advanced breast cancer, has demonstrated significant efficacy in prolonging progression-free survival when added to existing therapies. Considering the high cost of PAL, we assessed cost-effectiveness of adding PAL to usual care in treatment of advanced breast cancer. METHODS: We developed a discrete event simulation model to simulate time to cancer progression and to compare life time clinical benefit and cost of alternative treatment strategies for patients with metastatic disease from societal perspective. Per approved indication, endocrine treatment naive patients were assigned to PAL plus letrozole (PAL + LET) or letrozole alone (LET). Patients with prior endocrine therapy were assigned to PAL plus fulvestrant (FUL) (PAL + FUL) or FUL alone. The model assumptions were informed based on published clinical trial data and other peer reviewed studies. We carried out one-way and probabilistic sensitivity analyses to assess the robustness of our results to the changes in model assumptions. RESULTS: In treatment-naive patients, the addition of PAL to LET cost an estimated $768 498 per additional quality-adjusted life-year (QALY) gained. The addition of PAL to FUL in patients with prior endocrine therapy cost an estimated $918 166 per QALY gained. Sensitivity analyses demonstrated adding PAL has a 0% chance of being cost-effectiveness in either patient groups at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSION: From a societal perspective, PAL treatment of both patient groups (with and without prior endocrine therapy) is highly unlikely to be cost-effective compared with the usual care in the USA.

Impact of hospitalization on medication adherence estimation in claims data.

WHAT IS KNOWN AND OBJECTIVE: Pharmacy claims are commonly used to assess medication adherence. It is unclear how different approaches to handling hospitalizations compare to the gold standard of using outpatient and inpatient drug data. This study aimed to compare the impact of different approaches to handling hospitalizations on medication adherence estimation in administrative claims data. METHODS: We identified ß-blocker initiators after myocardial infarction (MI) and statin initiators regardless of hospitalization histories in the population-based, Taiwan database, which includes outpatient and inpatient drug claims data. Adherence to ß-blockers or to statins during a 365-day follow-up period was estimated in outpatient pharmacy claims using the proportion of days covered (PDC) in three ways: ignoring hospitalizations (PDC1); subtracting hospitalized days from the denominator (PDC2); and assuming drug use on all hospitalized days (PDC3). We compared these to an approach that incorporated inpatient drug use (PDC4). We also used a hypothetical example to examine variations across approaches in several scenarios, such as increasing hospitalized days. RESULTS AND DISCUSSION: Mean 365-day PDC was 74% among 1729 post-MI ß-blocker initiators (range: 73.1%-74.9%) and 44% among 69 435 statins initiators (range: 43.5%-44.0%), which varied little across approaches. Differences across approaches increased with increasing number of hospitalized days. For patients hospitalized for >28 days, mean difference across approaches was >15%. PDC3 consistently yielded the highest value and PDC1 the lowest. WHAT IS NEW AND CONCLUSIONS: On average, different approaches to handling hospitalizations lead to similar adherence estimates to the gold standard of incorporating inpatient drug use. When patients have many hospitalization days during follow-up, the choice of approach should be tailored to the specific setting.

Temporal trends in adherence to cardiovascular medications in elderly patients after hospitalization for heart failure.

Although the complexity of treatment regimens for patients with heart failure (HF) has increased over time because of the increased availability of efficacious medications, little is known about temporal trends in adherence to treatment regimens in these patients. We assessed trends in adherence to angiotensin-system blockers (ABs), ß-blockers (BBs), and spironolactone (SL) for HF in Medicare beneficiaries enrolled in two statewide pharmacy benefit programs from 1995 to 2004. The proportion of days covered (PDC) (%) was assessed after the first dispensing among users of an AB, BB, or SL. Proportions of full adherence (PDC >80%) did not change over time for ABs (54% in both 1996 and 2003) but increased slightly for BBs (from 47% in 1996 to 57% in 2003) and SL (from 31% in 1996 to 42% in 2003). Black race and dialysis treatment predicted poor adherence to any medications. Adherence to BBs and SL increased modestly over time, but overall nonadherence remained high.

The rational clinical examination. Does this patient have aortic regurgitation?

OBJECTIVE: To review evidence as to the precision and accuracy of clinical examination for aortic regurgitation (AR). METHODS: We conducted a structured MEDLINE search of English-language articles (January 1966-July 1997), manually reviewed all reference lists of potentially relevant articles, and contacted authors of relevant studies for additional information. Each study (n = 16) was independently reviewed by both authors and graded for methodological quality. RESULTS: Most studies assessed cardiologists as examiners. Cardiologists' precision for detecting diastolic murmurs was moderate using audiotapes (kappa = 0.51) and was good in the clinical setting (simple agreement, 94%). The most useful finding for ruling in AR is the presence of an early diastolic murmur (positive likelihood ratio [LR], 8.8-32.0 [95% confidence interval [CI], 2.8-32 to 16-63] for detecting mild or greater AR and 4.0-8.3 [95% CI, 2.5-6.9 to 6.2-11] for detecting moderate or greater AR) (2 grade A studies). The most useful finding for ruling out AR is the absence of early diastolic murmur (negative LR, 0.2-0.3 [95% CI, 0.1-0.3 to 0.2-0.4) for mild or greater AR and 0.1 [95% CI, 0.0-0.3] for moderate or greater AR) (2 grade A studies). Except for a test evaluating the response to transient arterial occlusion (positive LR, 8.4 [95% CI, 1.3-81.0]; negative LR, 0.3 [95% CI, 0.1-0.8]), most signs display poor sensitivity and specificity for AR. CONCLUSION: Clinical examination by cardiologists is accurate for detecting AR, but not enough is known about the examinations of less-expert clinicians.

Accuracy of clinical impressions and Mini-Mental State Exam scores for assessing capacity to consent to major medical treatment. Comparison with criterion-standard psychiatric assessments.

The authors evaluated the accuracy of clinical impressions and Mini-Mental State Exam scores for assessing patient capacity to consent to major medical treatment, relative to expert psychiatric assessment. Consecutive medical inpatients (N = 63) facing a decision about major medical treatment received a clinical impression of capacity from their treating physician and the Standardized Mini-Mental State Exam (SMMSE); 48 received independent psychiatric assessment of capacity. Analyses revealed that both clinical impressions and SMMSE scores were generally inaccurate in determining capacity, although all 23 participants with a clinical impression of "definitely capable" were found capable by the psychiatrist. Given the importance of assessing capacity to consent to major medical treatment, better approaches to the clinical assessment of capacity are required. Several strategies are discussed.

The relation of conjunctival pallor to the presence of anemia.

OBJECTIVE: To determine the value of conjunctival pallor in ruling in or ruling out the presence of severe anemia (hemoglobin < or = 90 g/L) and to determine the interobserver agreement in assessing this sign. DESIGN: Patients were prospectively assessed for pallor by at least one of three observers. All observations were made without information of the patient's hemoglobin value or of another observer's assessment. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENTS: Three hundred and two medical and surgical inpatients. MEASUREMENTS AND MAIN RESULTS: Likelihood ratios (LRs) calculated for conjunctival pallor present, borderline, and absent were as follows: pallor present, LR 4.49 (95% confidence interval [CI] 1.80, 10.99); pallor borderline, LR 1.80 (95% CI 1.18, 2.62); pallor absent, LR 0.61 (95% CI 0.44, 0.80). Kappa scores of interobserver agreement between paired observers were 0.75 and 0.54. CONCLUSIONS: The presence of conjunctival pallor, without other information suggesting anemia, is reason enough to perform a hemoglobin determination. The absence of conjunctival pallor is not likely to be of use in ruling out severe anemia. With well-defined criteria, interobserver agreement is good to very good.

Reflections on supply-demand mismatch in dialysis services in Ontario.

The population-based dialysis rate in Ontario more than doubled between 1981 and 1992; yet there is concern about over-loaded facilities, delayed treatment and denial of dialysis through nonreferral and implicit rationing. A working party involving several stakeholders has been established in Ontario to address these issues. However, clinical policy making concerning dialysis services is impeded in all provinces by a lack of information. The causes of the moderately large variations in dialysis rates from province to province remain unclear. The exact extent and risks of delayed therapy have not been well defined. Dialysis protocols vary inexplicably among centres, and cost data on different methods of providing dialysis are limited. Many steps could be taken in Ontario and other provinces to generate a better information base for planning and managing dialysis services. Predialysis clinics with outreach programs could help to ensure equitable access to this life-saving therapy. Criteria for choosing modes and intensities of renal-replacement therapy must be reviewed. In areas of clear disagreement and uncertainty, patients could be randomly assigned to different protocols and outcomes studied. In areas of agreement, the criteria should be standardized. Advance directives may help ascertain patients' wishes concerning the initiation or continuation of dialysis, and more accurate data on prognosis of different patient subgroups would aid in early identification of patients in a hopelessly deteriorating situation. Last, studies comparing the "output" (e.g., hours on hemodialysis) per dollar of different dialysis units and modalities are also needed to ensure that all facilities are opening efficiently without compromising patient outcomes.

Long-term care facility policies on life-sustaining treatments and advance directives in Canada.

OBJECTIVE: To describe the prevalence and content of long-term care facility policies regarding the use of life-sustaining treatments (cardiopulmonary resuscitation (CPR), artificial hydration and nutrition, dialysis, antibiotics for life-threatening infections, transfer to acute care hospital) and advance directives in Canada. DESIGN: Cross-sectional mailed survey. SETTING: Canadian long-term care facilities with 25 beds or more listed in the 1991-92 Directory of Long Term Care Centres in Canada. Institutions listed as, "general hospitals," "psychiatric hospitals," "children's treatment centres," "group homes," or as purely residential facilities were excluded. PARTICIPANTS: Chief Executive Officers or their designates. MAIN OUTCOME MEASURES: Respondents' self-reports regarding the existence of life-sustaining treatment or advance directive policies and content analysis of the policies themselves. RESULTS: Of 1472 long-term care facilities, 1021 (69%) responded. Of these, 344 (34%) institutions had 397 policies regarding the use of life-sustaining treatments or advance directives. Three hundred twenty facilities (31%) had 349 do-not-resuscitate (DNR) policies (40% on CPR alone and 60% on CPR plus other life-sustaining treatments). Seventeen institutions (2%) each had one policy addressing life-sustaining treatments other than CPR, and 31 institutions (3%) each had one policy addressing advance directives. Of the 397 policies, 171 (43%) required routine discussion with all patients, 156 (39%) mentioned futility, 331 (83%) indicated that the competent patient had the right to make a decision about life-sustaining treatment, 265 (67%) indicated that the family of the incompetent patient had this right, 27 policies (7%) mentioned conflict resolution, 378 (95%) had an explicit requirement for recording the decision, 10 (3%) required explicit communication of the decision to the competent patient, 10 (3%) required such communication to the family of the incompetent patient, 260 (66%) required updating of the decision, and 213 (54%) mentioned rescinding or changing the decision. CONCLUSIONS: Only one-third of Canadian long-term care facilities have do-not-resuscitate policies, and even fewer have policies on advance directives or life-sustaining treatments other than CPR. The policies themselves could be improved by encouraging routine advance discussions, scrutinizing the use of the futility standard, stipulating procedures for conflict resolution, and explicitly requiring communication of the decision to competent patients or substitute decision makers of incompetent patients.