Prognostic Testing and Treatment Patterns in Chronic Lymphocytic Leukemia in the Era of Novel Targeted Therapies: Results From the informCLL Registry.

INTRODUCTION: The therapeutic landscape for chronic lymphocytic leukemia (CLL) has significantly shifted with the approval of novel agents. Understanding current prognostic testing and treatment practices in this new era is critical. Beginning enrollment in 2015, informCLL is the first United States-based real-world, prospective, observational registry that initiated enrollment after approval of novel agents. PATIENTS AND METHODS: Eligible patients were age ≥ 18 years, started CLL treatment within 30 days of enrollment, and provided consent. For this planned interim analysis, treatments were classified into 5 groups: ibrutinib, chemoimmunotherapy, chemotherapy, immunotherapy, and other novel agents. RESULTS: Frequency of prognostic testing and treatment patterns are reported among 840 patients (459 previously untreated; 381 relapsed/refractory), enrolled largely (96%) from community practice settings. Testing for chromosomal abnormalities by fluorescence in situ hybridization, TP53 mutation, or IGHV mutation status occurred infrequently among all patients (31%, 11%, and 11%, respectively). Chemoimmunotherapy was the most common treatment in previously untreated patients (42%), whereas ibrutinib was the most common treatment among relapsed/refractory patients (51%). Of patients who tested positive for del(17p) or TP53 mutation, 34% and 26% received chemoimmunotherapy, respectively. Among patients who did not have fluorescence in situ hybridization or TP53 mutation testing prior to enrollment, 33% and 32% received chemoimmunotherapy, respectively. CONCLUSION: Our findings indicate that prognostic testing rates were poor, and approximately one-third of high-risk patients (del[17p] and TP53) received chemoimmunotherapy, which is not aligned with current CLL treatment recommendations. This represents an opportunity to educate and alert health care professionals about the necessity of prognostic testing to guide optimal CLL treatment decisions.

Medication Nonadherence Among Medicare Beneficiaries with Comorbid Chronic Conditions: Influence of Pharmacy Dispensing Channel.

BACKGROUND: Taking medications as prescribed is imperative for their effectiveness. In populations such as Medicare, where two thirds of Medicare beneficiaries have at least 2 or more chronic conditions requiring treatment with medications and account for more than 90% of Medicare health care spend, examining ways to improve medication adherence in patients with comorbidities is warranted. OBJECTIVE: To examine the association of pharmacy dispensing channel (home delivery or retail pharmacy) with medication adherence for Medicare patients taking medications with comorbid conditions of diabetes, hypertension, and high blood cholesterol (3 of the top 5 most prevalent conditions), while controlling for various confounders. METHODS: A retrospective analysis was conducted using de-identified pharmacy claims data from a large national pharmacy benefits manager between October 2010 and December 2012. Continuously eligible Medicare Part D patients (Medicare Advantage Prescription Drug plan and Prescription Drug Plan only) aged 65 years or older who had an antidiabetic, antihypertensive, and antihyperlipidemic prescription claim between October and December 2010 were identified and analyzed over a 2-year period. Multivariate logistic regression was used to evaluate the association between dispensing channel (DC) and medication adherence in calendar year (CY) 2012 controlling for prior adherence behavior (adherence in CY2011), differences in demographics, low-income subsidy status, days supply, disease burden, and drug-use pattern. Patients with a proportion of days covered (PDC) of at least 80% for each of the 3 conditions were considered to be adherent, and patients with PDC less than 80% for each of the 3 conditions were considered to be nonadherent. Patients were assigned to a DC depending on where they filled at least 66.7% of their prescriptions for each of the 3 conditions, and the rest were assigned to a mixed channel group. RESULTS: The final analytical sample consisted of 40,632 patients. The adjusted odds of adherence for patients using home delivery were 1.59 (95% CI = 1.40-1.80) higher compared with patients using retail channels to obtain their prescriptions. CONCLUSIONS: Medicare Part D patients taking medications for comorbid conditions who used home delivery had a greater likelihood (adjusted) of adherence than patients who filled their antidiabetic, antihypertensive, and antihyperlipidemic prescriptions using retail channels. Managed care stakeholders looking to make informed decisions in a cost-constrained environment to assess, implement, and promote solutions that improve health outcomes should consider the use of home delivery of prescriptions to improve adherence for Medicare Part D patients with comorbid conditions. DISCLOSURES: Funding for this study was provided internally by Express Scripts Holding Company. Iyengar, LeFrancois, Henderson, and Rabbitt are employees of Express Scripts. Study concept and design were created by Iyengar and LeFrancois. Iyengar was responsible for acquisition of data, statistical analysis, and interpretation of data. The manuscript was written by Iyengar and LeFrancois and revised by all the authors.

A Tool to Assess Risk of De Novo Opioid Abuse or Dependence.

BACKGROUND: Determining risk factors for opioid abuse or dependence will help clinicians practice informed prescribing and may help mitigate opioid abuse or dependence. The purpose of this study is to identify variables predicting opioid abuse or dependence. METHODS: A retrospective cohort study using de-identified integrated pharmacy and medical claims was performed between October 2009 and September 2013. Patients with at least 1 opioid prescription claim during the index period (index claim) were identified. We ascertained risk factors using data from 12 months before the index claim (pre-period) and captured abuse or dependency diagnosis using data from 12 months after the index claim (postperiod). We included continuously eligible (pre- and postperiod) commercially insured patients aged 18 years or older. We excluded patients with cancer, residence in a long-term care facility, or a previous diagnosis of opioid abuse or dependence (identified by International Classification of Diseases 9th revision code or buprenorphine/naloxone claim in the pre-period). The outcome was a diagnosis of opioid abuse (International Classification of Diseases 9th revision code 304.0x) or dependence (305.5). RESULTS: The final sample consisted of 694,851 patients. Opioid abuse or dependence was observed in 2067 patients (0.3%). Several factors predicted opioid abuse or dependence: younger age (per decade [older] odds ratio [OR], 0.68); being a chronic opioid user (OR, 4.39); history of mental illness (OR, 3.45); nonopioid substance abuse (OR, 2.82); alcohol abuse (OR, 2.37); high morphine equivalent dose per day user (OR, 1.98); tobacco use (OR, 1.80); obtaining opioids from multiple prescribers (OR, 1.71); residing in the South (OR, 1.65), West (OR, 1.49), or Midwest (OR, 1.24); using multiple pharmacies (OR, 1.59); male gender (OR, 1.43); and increased 30-day adjusted opioid prescriptions (OR, 1.05). CONCLUSIONS: Readily available demographic, clinical, behavioral, pharmacy, and geographic information can be used to predict the likelihood of opioid abuse or dependence.

Utilization and Costs of Compounded Medications for Commercially Insured Patients, 2012-2013.

BACKGROUND: Although compounding has a long-standing tradition in clinical practice, insurers and pharmacy benefit managers have instituted policies to decrease claims for compounded medications, citing questions about their safety, efficacy, high costs, and lack of FDA approval. There are no reliable published data on the extent of compounding by community pharmacists nor on the fraction of patients who use compounded medications. Prior research suggests that compounded medications represent a relatively small proportion of prescription medications, but those surveys were limited by small sample sizes, subjective data collection methods, and low response rates. OBJECTIVE: To determine the number of claims for compounded medications on a per user per year (PUPY) basis and the average ingredient cost of these claims among commercially insured patients in the United States for 2012 and 2013. METHODS: This study used prescription claims data from a nationally representative sample of commercially insured members whose pharmacy benefits were managed by a large pharmacy benefit management company. A retrospective claims analysis was conducted from January 1, 2012, through December 31, 2013. Annualized prevalence, cost, and utilization estimates were drawn from the data. All prescription claims were adjusted to 30-day equivalents. Data-mining techniques (association rule mining) were employed in order to identify the most commonly combined ingredients in compounded medications. RESULTS: The prevalence of compound users was 1.1% (245,285) of eligible members in 2012 and 1.4% (323,501) in 2013, an increase of 27.3%. Approximately 66% of compound users were female, and the average age of a compound user was approximately 42 years throughout the study period. The geographic distribution of compound user prevalence was consistent across the United States. Compound users' prescription claims increased 36.6% from 2012 to 2013, from approximately 7.1 million to approximately 9.7 million prescriptions. The number of claims for compounded medications increased by 34.2% during the same period, from 486,886 to 653,360. PUPY utilization remained unchanged at 2 prescriptions from 2012 to 2013. The most commonly compounded drugs were similar for all adult age groups and represented therapies typically indicated for chronic pain or hormone replacement therapy. The average ingredient cost for compounded medications increased by 130.3% from 2012 to 2013, from $308.49 to $710.36. The average ingredient cost for these users' non-compounded prescriptions increased only 7.7%, from $148.75 to $160.20. For comparison, the average ingredient cost for all prescription users' claims was $81.50 in 2012 and increased by 3.8% to $84.57 in 2013. CONCLUSIONS: Compound users represented 1.4% of eligible members in 2013. The average ingredient cost for compound users' compounded prescriptions ($710.36) was greater than for noncompounded prescriptions ($160.20). The 1-year increase in average compounded prescription costs (130.3%) was also greater than for noncompounded prescriptions (7.7%). Although prevalence of compound users and the PUPY utilization for compounded prescriptions increased only slightly between 2012 and 2013, the mean and median cost of compounded medications increased dramatically during this time. Text mining revealed that drug combinations characteristic of topical pain formulations were among the most frequently compounded medications for adults.

Association between dispensing channel and medication adherence among medicare beneficiaries taking medications to treat diabetes, high blood pressure, or high blood cholesterol.

BACKGROUND: Medication adherence, defined as taking medications as prescribed, is a key component in controlling disease progression and managing chronic illnesses such as diabetes, hypertension, and high blood cholesterol. These diseases constitute 3 of the top 5 most prevalent conditions among Medicare beneficiaries, warranting further attention to find ways to promote better medication adherence. The scientific literature has established the clinical and financial benefits of medication adherence and the role of dispensing channel in impacting adherence to medications. However, a common limitation in channel-adherence studies is the failure to control for healthy adherer effect (HAE), referring to individuals who are likely to engage proactively in activities that improve their adherence. Healthier individuals may choose the home-delivery channel to ensure continuity in their medication regimens and to minimize obstacles to adherence, such as inadequate access, inconvenience, and financial concerns. Thus, better medication adherence in home delivery may reflect healthier patients' predisposition to self-select for home delivery options. To accurately attribute the impact of dispensing channel on adherence, research would need to control for bias from a patient's predisposition to be adherent.  OBJECTIVE: To examine the association of pharmacy dispensing channel (home delivery or retail pharmacy) with medication adherence for Medicare Part D beneficiaries taking medications for diabetes, hypertension, or high blood cholesterol, while controlling for low-income subsidy status, differences in days supply, and prior adherence behavior (PAB) as a way to partly control for HAE. METHODS: A retrospective analysis using de-identified pharmacy claims data from a large national pharmacy benefits manager between October 2010 and December 2012. Continuously eligible Medicare Part D beneficiaries (Medicare Advantage and prescription drug plans participants only) aged 65 years or older who had an antidiabetic, antihypertensive, or antihyperlipidemic prescription claim between October and December 2010, were identified and followed for the next 2 years. Those enrolled in a home delivery auto refill program were excluded from this analysis. Multivariate logistic regression was used to evaluate the impact of dispensing channel on medication adherence, controlling for differences in demographics, low-income subsidy status, disease burden, and drug-use pattern. Patients with a proportion of days covered of ≥ 80% were considered to be adherent. The analysis controlled for PAB by using patients' adherence status in the year 2011.  RESULTS: The final analytical samples consisted of 150,389 diabetic patients, 615,618 hypertension patients, and 358,795 high blood cholesterol patients. The adjusted odds of being adherent for beneficiaries using home delivery were 1.25 times higher (CI = 1.20-1.30) for diabetes medications, 1.29 times higher (CI = 1.27-1.32) for hypertension medications, and 1.26 times higher (CI = 1.23-1.29) for high blood cholesterol medications, compared with beneficiaries using retail channels to obtain their prescriptions. PAB was the strongest contributor to the odds of a patient being adherent across all 3 therapy classes, ranging from odds ratio of 4.48 to 8.09.  CONCLUSIONS: After excluding patients who received any prescriptions via home delivery auto refill programs and controlling for PAB, differences in days supply, low-income subsidy status, demographics, and disease burden, Medicare beneficiaries who use home delivery for antidiabetics, antihypertensives, or antihyperlipidemics have a greater likelihood of being adherent than patients who fill their prescriptions at retail. The results of this study provide evidence that where medications are received may impact adherence, even when controlling for PAB. Use of the home delivery dispensing channel may be an effective method to improve adherence for Medicare beneficiaries.

Dispensing channel and medication adherence: evidence across 3 therapy classes.

OBJECTIVES: To examine the association of mail order versus retail pharmacy dispensing channels with medication adherence for patients on diabetes, hypertension, or high blood cholesterol medications, controlling for prior adherence behavior (PAB) and days of supply. STUDY DESIGN: Retrospective analysis using de-identified pharmacy claims data from a large national pharmacy benefits manager between April 2009 and December 2011. METHODS: Continuously eligible patients with an antidiabetic, antihypertensive, or antihyperlipidemic prescription claim between October and December 2009 were identified and followed over a 2-year period. Multivariate logistic regression was used to evaluate the impact of dispensing channel on medication adherence, controlling for differences in demographics, disease burden, and drug use pattern. Patients with a medication possession ratio of 80% or greater were considered adherent. The analysis controlled for PAB by using patients' adherence status in 2010. RESULTS: Overall, patients using the mail order channel had higher adherence rates than their retail counterparts across all 3 therapeutic classes. In 2011, the likelihood of a mail order patient being adherent was approximately 1.15 times higher than that of a retail patient for antidiabetics, 1.11 times higher for antihypertensives, and 1.19 times higher for antihyperlipidemics. PAB was the strongest contributor to the odds of a patient being adherent across all 3 therapy classes: odds ratios ranged from 5.87 to 9.49. CONCLUSIONS: After adjusting for PAB, differential days of supply, and differences in demographics and disease burden, patients who use mail order have a greater likelihood of being adherent than patients who use a retail pharmacy.

Does sepsis treatment differ between primary and overflow intensive care units?

BACKGROUND: Sepsis is a major cause of death in hospitalized patients. Early goal-directed therapy is the standard of care. When primary intensive care units (ICUs) are full, sepsis patients are cared for in overflow ICUs. OBJECTIVE: To determine if process-of-care measures in the care of sepsis patients differed between primary and overflow ICUs at our institution. DESIGN: We conducted a retrospective study of all adult patients admitted with sepsis between July 2009 and February 2010 to either the primary ICU or the overflow ICU. MEASUREMENTS: Baseline patient characteristics and multiple process-of-care measures, including diagnostic and therapeutic interventions. RESULTS: There were 141 patients admitted with sepsis to our hospital; 100 were cared for in the primary ICU and 41 in the overflow ICU. Baseline acute physiology and chronic health evaluation (APACHE II) scores were similar. Patients received similar processes-of-care in the primary ICU and overflow ICU with the exception of deep vein thrombosis (DVT) and gastrointestinal (GI) prophylaxis within 24 hours of admission, which were better adhered to in the primary ICU (74% vs 49%, P = 0.004, and 68% vs 44%, P = 0.012, respectively). There were no significant differences in hospital and ICU length of stay between the 2 units (9.68 days vs 9.73 days, P = 0.98, and 4.78 days vs 4.92 days, P = 0.97, respectively). CONCLUSIONS: Patients with sepsis admitted to the primary ICU and overflow ICU at our institution were managed similarly. Overflowing sepsis patients to non-primary intensive care units may not affect guideline-concordant care delivery or length of stay.

Performance evaluation of ambulatory surgery centres: an efficiency approach.

This paper evaluates the performance of 198 ambulatory surgery centres (ASCs) operating in the State of Pennsylvania during the fiscal year 2006. Performance is assessed from technical efficiency view using data envelopment analysis (DEA). Multi-input/output model included two inputs: number of operating rooms and labour, and patient surgical visits differentiated by age groups: 0-17, 18-64, 65+ as three outputs. Input oriented models were employed to assess various DEA efficiency models. Results show that about 48 (24%) of ASCs are efficient with a mean efficiency score of 0.60. The results also indicate that appropriate utilization of operating rooms and labour inputs are the main determinants of ASC efficiency.