Offering Lung Cancer Screening to High-Risk Medicare Beneficiaries Saves Lives and Is Cost-Effective: An Actuarial Analysis

Background

By a wide margin, lung cancer is the most significant cause of cancer death in the United States and worldwide. The incidence of lung cancer increases with age, and Medicare beneficiaries are often at increased risk. Because of its demonstrated effectiveness in reducing mortality, lung cancer screening with low-dose computed tomography (LDCT) imaging will be covered without cost-sharing starting January 1, 2015, by nongrandfathered commercial plans. Medicare is considering coverage for lung cancer screening.

Objective

To estimate the cost and cost-effectiveness (ie, cost per life-year saved) of LDCT lung cancer screening of the Medicare population at high risk for lung cancer.

Methods

Medicare costs, enrollment, and demographics were used for this study; they were derived from the 2012 Centers for Medicare & Medicaid Services (CMS) beneficiary files and were forecast to 2014 based on CMS and US Census Bureau projections. Standard life and health actuarial techniques were used to calculate the cost and cost-effectiveness of lung cancer screening. The cost, incidence rates, mortality rates, and other parameters chosen by the authors were taken from actual Medicare data, and the modeled screenings are consistent with Medicare processes and procedures.

Results

Approximately 4.9 million high-risk Medicare beneficiaries would meet criteria for lung cancer screening in 2014. Without screening, Medicare patients newly diagnosed with lung cancer have an average life expectancy of approximately 3 years. Based on our analysis, the average annual cost of LDCT lung cancer screening in Medicare is estimated to be $241 per person screened. LDCT screening for lung cancer in Medicare beneficiaries aged 55 to 80 years with a history of ≥30 pack-years of smoking and who had smoked within 15 years is low cost, at approximately $1 per member per month. This assumes that 50% of these patients were screened. Such screening is also highly cost-effective, at <$19,000 per life-year saved.

Conclusion

If all eligible Medicare beneficiaries had been screened and treated consistently from age 55 years, approximately 358,134 additional individuals with current or past lung cancer would be alive in 2014. LDCT screening is a low-cost and cost-effective strategy that fits well within the standard Medicare benefit, including its claims payment and quality monitoring.Lung cancer is a lethal disease that claims the lives of more people in the United States annually than the next 4 most lethal cancers combined, which are, in order, colon, breast, pancreas, and prostate cancers.1,2 In the United States, an estimated 224,210 people will be diagnosed with lung cancer, and an estimated 159,260 people will die of the disease in 2014.3 The incidence of lung cancer increases with age,4 and the risk increases with the cumulative effects of past smoking. Millions of Medicare beneficiaries are at significant risk.5On December 31, 2013, lung cancer screening using low-dose computed tomography (LDCT) was rated as a level “B” recommendation by the US Preventive Services Task Force (USPSTF),6 a panel of independent experts convened by the Agency for Healthcare Research and Quality to evaluate the strength of evidence and the balance of benefits and harms of preventive services.7 The USPSTF recommendation applies to people aged 55 to 80 years with a history of heavy smoking.6 LDCT is an imaging technology that enables 3-dimensional visualization of internal body structures, including the lungs, using low doses of radiation.Under the Affordable Care Act, the “B” recommendation means that LDCT lung cancer screening must be covered without cost-sharing by qualified health plans starting January 1, 2015.6,8 Qualified health plans include commercial insurance and self-insured benefit plans, with the exclusion of grandfathered plans. Several private insurers have initiated LDCT screening coverage in advance of the 2015 requirement.9 Furthermore, versions of the USPSTF recommendations have been adopted essentially by every major academic body with an interest in lung cancer, including the National Comprehensive Cancer Network, American Association for Thoracic Surgery, American College of Radiology, Society of Thoracic Surgeons, International Association for the Study of Lung Cancer, American College of Chest Physicians, and the American Cancer Society.Medicare has begun a national coverage analysis to determine whether LDCT lung cancer screening meets its criteria for coverage, which includes whether screening is reasonable and necessary for early detection, whether the service has an “A” or a “B” recommendation by the USPSTF, and whether screening is appropriate for Medicare beneficiaries.High doses of radiation can be harmful. LDCT can be performed at very low doses of <0.7 mSv per procedure10 by comparison, the annual natural background radiation in New York City (sea level) is 3 mSv. LDCT technology refinements and protocol optimization have translated into patient benefits, supporting the detection of ever-smaller lung cancers, reducing the rate of surgical procedures, and providing higher cure rates.11–14Advances in LDCT technology, promising results from nonrandomized trials,14 and unchanged survival statistics over the previous 30 years, led to the implementation of the National Lung Screening Trial (NLST), the most expensive and one of the largest randomized screening trials ever sponsored by the National Cancer Institute.13 The trial of 53,454 people aged 55 to 74 years at high risk for lung cancer was conducted to determine whether LDCT screening could reduce mortality from lung cancer. Participants in this 2-arm US study received 3 annual screenings with either an LDCT or a chest x-ray. Based on the study protocol, the trial was stopped when findings demonstrated a relative reduction of 20% in lung cancer mortality in the LDCT arm versus the chest x-ray arm.13Observational data and epidemiologic arguments for breast cancer also suggest that additional rounds of screening would reduce lung cancer mortality by much more than 20%.15–22 Other large studies have shown that computed tomography (CT) screening is associated with a high proportion (much higher than 70%) of the lung cancer diagnoses being early stage15–17,21 compared with 15% in the national data.23 Long-term survival rates of approximately 80% have been reported for patients with lung cancer who are diagnosed by CT screening12,15,16 compared with a 16.8% 5-year survival rate from the national data.23

KEY POINTS

• ▸ Lung cancer is the leading cause of cancer death in the United States and worldwide.
• ▸ Because the risk increases with age and with a history of smoking, some Medicare beneficiaries are at high risk for this type of cancer.
• ▸ Low-dose computed tomography (LDCT) has been shown to reduce mortality from lung cancer by more than 20%.
• ▸ Under healthcare reform, LDCT must be covered without cost-sharing by nongrandfathered commercial health plans beginning in 2015.
• ▸ Based on this new analysis, LDCT screening of high-risk Medicare beneficiaries is cost-effective and will cost approximately $1 per member per month.
• ▸ The average annual cost of such a screening policy is estimated to be $241 for a Medicare beneficiary screened.
• ▸ Given all causes of mortality, without screening, Medicare patients newly diagnosed with lung cancer have an average of 3 years life expectancy.
• ▸ With screening, these patients would have an additional 4 years of additional life expectancy incremental to the life expectancy without screening.
• ▸ If all eligible beneficiaries had been screened and treated consistently from age 55 years, approximately 358,134 additional individuals with current or past lung cancer would be alive in 2014.

One of the coauthors of this article was the lead author of an actuarial analysis of LDCT lung cancer screening for the commercially insured population.24 This report used similar methodology, types of structures, and data to examine lung cancer screening for the Medicare program. The Medicare program faces significant budget limitations, and any new coverage benefit will face scrutiny regarding its costs and benefits.The purpose of the present study was to estimate the hypothetical 2014 costs and benefits associated with the responsible implementation of widespread lung cancer screening in the high-risk US population covered by Medicare.     

Evolving Trends in Insulin Delivery In Pursuit of Improvements in Diabetes Management

Diabetes mellitus affects 23.6 million Americans and its incidence is rapidly increasing, particularly in older, overweight patients. Large-scale studies conclusively show that elevated blood glucose levels are associated with an increased risk for microvascular complications, such as retinopathy and nephropathy. The high rates of morbidity and mortality associated with this disease, and the costs associated with it, underscore the importance of effective glycemic control. Conventional syringe/vial insulin delivery is associated with many barriers for patients with diabetes mellitus and for their healthcare providers. Substantial developments in insulin delivery show promise in overcoming these barriers. New technologies in insulin delivery focus on increasing patient convenience, reducing the frequency of daily injections, and improving glycemic control. This article outlines the challenges associated with conventional insulin delivery and describes recent developments that may help to overcome these barriers and, ultimately, could enhance glycemic control.Diabetes mellitus affects 23.6 million Americans, or about 8% of the US population.1 This includes nearly 18 million persons with diagnosed disease and about 5.7 million undiagnosed cases. The incidence of type 2 diabetes is rapidly increasing, particularly among older, overweight persons who have concomitant cardiovascular (CV) risks.2 The coexistence of diabetes mellitus and hypertension works synergistically to increase morbidity and mortality, especially renal and CV injury.3 Well-known, large-scale studies, such as the Diabetes Control and Complications Trial and the UK Prospective Diabetes Study, conclusively show that elevated levels of blood glucose are associated with an increased risk of microvascular complications, such as retinopathy and nephropathy.4–6 The high rates of morbidity and mortality associated with diabetes, coupled with the costs of treating these sequelae, underscore the importance of effective glycemic control.Maintaining optimal glucose control—defined by the American Diabetes Association as a glycosylated hemoglobin level of <7%7—may require multiple daily insulin injections. However, conventional insulin injection techniques are a major cause of reduced patient adherence to treatment.8 Patient medication adherence and satisfaction with treatment regimens are more likely to occur with fewer medication side effects, as well as with reduced patient burden and inconvenience.9,10 Typical side effects of insulin therapy may include weight gain or hypoglycemic events.2,11Significant advances in insulin delivery have been aimed at improving patient convenience and enhancing glycemic control.12 Alternatives to syringe/vial insulin delivery include:

• Insulin pens
• Injection ports
• Insulin infusion pumps
• Transdermal insulin patches
• Inhaled insulin.

Some of these methods, however, have not met with great success. Inhalable insulin was available in the United States from September 2006 through October 2007 but was subsequently withdrawn from the market because of poor utilization rates. Other advances currently in development include oral insulin and buccal insulin spray. An international phase 3 clinical trial is ongoing for both types of insulin delivery.This article reviews the barriers to adherence to conventional therapy and evaluates developments in the management of insulin-requiring diabetes that may help to overcome some of these barriers, as well as improve glycemic control and quality of life for patients with diabetes.

KEY POINTS

• ▸ Nearly 18 million Americans are diagnosed with diabetes, and about 5.7 million have the disease but have not been diagnosed.
• ▸ The high rates of morbidity and mortality associated with diabetes, and the costs associated with its treatment, underscore the importance of effective glycemic control.
• ▸ Conventional syringe/vial insulin delivery is associated with patient and physician barriers, such as psychological insulin resistance, patients'' fear of insulin side effects and complications, and required lifestyle changes/restrictions.
• ▸ Despite evidence that many patients with type 2 diabetes do not achieve glycemic control with oral therapy alone, some physicians are still reluctant to initiate insulin therapy.
• ▸ Developments in insulin delivery during the past 20 years have focused on increasing patient convenience and improved glycemic control.
• ▸ The newer insulin delivery modes include insulin pens, insulin injection ports, continuous subcutaneous insulin infusion pumps, transdermal patches, and inhalable devices.

     

National Burden of Preventable Adverse Drug Events Associated with Inpatient Injectable Medications: Healthcare and Medical Professional Liability Costs

Background

Harmful medication errors, or preventable adverse drug events (ADEs), are a prominent quality and cost issue in healthcare. Injectable medications are important therapeutic agents, but they are associated with a greater potential for serious harm than oral medications. The national burden of preventable ADEs associated with inpatient injectable medications and the associated medical professional liability (MPL) costs have not been previously described in the literature.

Objective

To quantify the economic burden of preventable ADEs related to inpatient injectable medications in the United States.

Methods

Medical error data (MedMarx 2009–2011) were utilized to derive the distribution of errors by injectable medication types. Hospital data (Premier 2010–2011) identified the numbers and the types of injections per hospitalization. US payer claims (2009–2010 MarketScan Commercial and Medicare 5% Sample) were used to calculate the incremental cost of ADEs by payer and by diagnosis-related group (DRG). The incremental cost of ADEs was defined as inclusive of the time of inpatient admission and the following 4 months. Actuarial calculations, assumptions based on published literature, and DRG proportions from 17 state discharge databases were used to derive the probability of preventable ADEs per hospitalization and their annual costs. MPL costs were assessed from state- and national-level industry reports, premium rates, and from closed claims databases between 1990 and 2011. The 2010 American Hospital Association database was used for hospital-level statistics. All costs were adjusted to 2013 dollars.

Results

Based on this medication-level analysis of reported harmful errors and the frequency of inpatient administrations with actuarial projections, we estimate that preventable ADEs associated with injectable medications impact 1.2 million hospitalizations annually. Using a matched cohort analysis of healthcare claims as a basis for evaluating incremental costs, we estimate that inpatient preventable ADEs associated with injectable medications increase the annual US payer costs by $2.7 billion to $5.1 billion, averaging $600,000 in extra costs per hospital. Across categories of injectable drugs, insulin had the highest risk per administration for a preventable ADE, although errors in the higher-volume categories of anti-infective, narcotic/analgesic, anticoagulant/thrombolytic and anxiolytic/sedative injectable medications harmed more patients. Our analysis of liability claims estimates that MPL associated with injectable medications totals $300 million to $610 million annually, with an average cost of $72,000 per US hospital.

Conclusion

The incremental healthcare and MPL costs of preventable ADEs resulting from inpatient injectable medications are substantial. The data in this study strongly support the clinical and business cases of investing in efforts to prevent errors related to injectable medications.Preventable medication errors have emerged as a prominent cost and quality issue in the United States, and are estimated to impact more than 7 million patients, contribute to 7000 deaths, and cost almost $21 billion in direct medical costs across all care settings annually.1,2 Adverse drug events (ADEs) are harms that result from medication use; when these harms result from a medication error, they are known as “preventable ADEs.”3 The inpatient hospital setting is particularly resource-intensive in terms of care delivered and exposure to potential harms and errors.4,5 In 2007, the Institute of Medicine (IOM) estimated that 1 medication error occurred per patient per day in hospital care.4 In 2008, the US Department of Health and Human Services (HHS) estimated that approximately 1 of every 7 (13.5%) hospitalized Medicare patients experienced permanent harm from a medical error, and that 37% of these inpatient injuries were associated with medications.5 In addition, the study investigators estimated that 50% of these ADEs were preventable.5The majority of hospitalized patients receive medications, which means that a high volume of doses are prescribed and are administered daily in the inpatient setting. A study in a 735-bed academic medical center estimated that approximately 16,000 medication doses were administered daily.6 This study and others report that up to 1 of 5 medication doses are associated with an error, and that between 3% and 7% of these errors are potentially harmful to patients.6,7Furthermore, many of the medications used in the inpatient setting are delivered by injectable routes; these injectable medications have among the highest risk for error and the most severe harms.8 In a study of inpatient ADEs, including life-threatening ADEs, 50% of the medications that were implicated were injectable, including antihypertensives, insulin, and anticoagulants.9 Similarly, studies in the inpatient intensive care unit setting, where medications delivered by infusion are common, have reported that a patient''s risk for a medication error is approximately 10%, with 1 in 100 errors causing harm that requires life-saving treatment.8,10In addition to the clinical harms caused by preventable ADEs, healthcare stakeholders incur the economic consequences as well. When a patient experiences a preventable ADE, there may be direct medical costs to payers, such as an extended inpatient stay, use of additional medications, and physician visits in an outpatient setting to restore the patient''s health. There are also indirect costs, which may include missed work, reduced quality of life, and disability for the patient, as well as possible uncompensated expenses for the healthcare provider. In a 1997 study, preventable ADEs were estimated to add $4685 in adjusted, postevent costs to an inpatient hospitalization, amounting to an additional $2.8 million in annual costs per hospital.11 Citing articles by Bates and colleagues and Classen and colleagues, the IOM estimates that preventable ADEs affect up to 450,000 hospitalized patients and add $3.5 billion in extra costs to hospitals annually.4,11,12

KEY POINTS

• ▸ Half of all adverse drug events (ADEs) are a result of medication errors and are therefore preventable.
• ▸ Injectable medications are among those at highest risk for error and can be associated with life-threatening events.
• ▸ This is the first analysis of the national burden of medication errors associated with inpatient injectable medications.
• ▸ The results show that preventable ADEs associated with injectable medications impact more than 1 million patients in the inpatient setting.
• ▸ Injectable-related preventable ADEs cause an increase of $2.7 billion to $5.1 billion in annual costs to US healthcare payers, with an average of $600,000 in extra annual cost per hospital.
• ▸ Furthermore, the analysis of liability claims shows a cost burden of $300 million to $610 million annually in medical professional liability, with an average cost of $72,000 per hospital.
• ▸ Reducing injectable medication errors and the associated preventable ADEs can improve quality of care for patients and reduce unnecessary cost for payers, hospitals, and physicians.
• ▸ The study''s broad approach to costs, including the 4 months after discharge and medical professional liability costs, is aligned with healthcare reform initiatives in the United States, where payers are introducing new payment structures that consider patient outcomes beyond the inpatient stay.

Lawsuits and administrative actions related to preventable ADEs also increase costs for healthcare stakeholders. Provider costs related to medical professional liability (MPL), once called “medical malpractice,” are substantial. A previous study of MPL claims estimated that 73% of ADE-related cases were preventable; although legal defense costs were similar for inpatient and outpatient ADEs, the legal settlement costs were greatest for inpatient ADEs, which averaged $376,500 per MPL case.13We conducted a comprehensive analysis of US payer and MPL costs for preventable ADEs related to injectable medications in the inpatient setting. We chose to focus this study on preventable ADEs resulting from injectable medications for several reasons, including their frequent use, their high risk for error, and their potential for targeted prevention strategies in the inpatient setting.14     

Sensitivity of Medication Use to Formulary Controls in Medicare Beneficiaries: A Review of the Literature

Background

Several studies have examined the impact of formulary management strategies on medication use in the elderly, but little has been done to synthesize the findings to determine whether the results show consistent trends.

Objective

To summarize the effects of formulary controls (ie, tiered copays, step edits, prior authorization, and generic substitution) on medication use in the Medicare population to inform future Medicare Part D and other coverage decisions.

Methods

This systematic review included research articles (found via PubMed, Google Scholar, and specific scientific journals) that evaluated the impact of drug coverage or cost-sharing on medication use in elderly (aged ≥65 years) Medicare beneficiaries. The impact of drug coverage was assessed by comparing patients with some drug coverage to those with no drug coverage or by comparing varying levels of drug coverage (eg, full coverage vs $1000 coverage or capped benefits vs noncapped benefits). Articles that were published before 1995, were not original empirical research, were published in languages other than English, or focused on populations other than Medicare beneficiaries were excluded. All studies selected were classified as positive, negative, or neutral based on the significance of the relationship (P <.05 or as otherwise specified) between the formulary control mechanism and the medication use, and on the direction of that relationship.

Results

Included were a total of 47 research articles (published between 1995 and 2009) that evaluated the impact of drug coverage or cost-sharing on medication use in Medicare beneficiaries. Overall, 24 studies examined the impact of the level of drug coverage on medication use; of these, 96% (N = 23) supported the association between better drug coverage (ie, branded and generic vs generic-only coverage, capped benefit vs noncapped benefit, supplemental drug insurance vs no supplemental drug insurance) or having some drug coverage and enhanced medication use. Furthermore, 84% (N = 16) of the 19 studies that examined the effect of cost-sharing on medication use demonstrated that decreased cost-sharing was significantly associated with improved medication use.

Conclusion

Current evidence from the literature suggests that restricting drug coverage or increasing out-of-pocket expenses for Medicare beneficiaries may lead to decreased medication use in the elderly, with all its potential implications.Patient access to healthcare resources is an important topic of healthcare discussion, research, and reform in the United States.1,2 Access issues are usually framed in the context of patients having health insurance, as the quality of health insurance facilitates patient access to necessary medical and pharmaceutical therapies.2 Although patient access to medications is essential, formulary management strategies may introduce barriers aimed at restricting utilization, including curbing patient demand by increasing the cost borne by the patient or providing incentives to select lower-cost alternatives. Examples of these strategies include tiered copays, coinsurance, and benefit caps.3,4

KEY POINTS

• ▸ Many studies have investigated the impact of formulary management (eg, tiered copays, step edits, prior authorization) on medication use (eg, adherence, change in days supply, medication fills) patterns in Medicare beneficiaries, but none has synthesized the findings to arrive at some common trends in this patient population.
• ▸ The present study reviewed 47 studies that had met the study criteria involving medication use by Medicare beneficiaries between 1995 and 2009.
• ▸ Among the 24 studies that investigated the impact of drug coverage on medication use, 23 showed that elderly patients with greater drug coverage are more likely to use their medications as prescribed than those with greater coverage restrictions.
• ▸ Of the 19 studies that examined the effect of cost-sharing on medication use, 16 demonstrated that decreased patient cost-sharing improved medication use.
• ▸ Overall, the evidence shows that more restrictive drug coverage is associated with reduced medication use among Medicare beneficiaries, and fewer restrictions encourage enhanced medication use.
• ▸ Health plans are facing increasing pressures to implement strategies to control costs, including drug costs; nevertheless, restricting access to necessary medications in the elderly may lead to suboptimal clinical outcomes and potentially greater medical expenditures.

The advent of Medicare Part D in 2006 made the federal government the single largest payer of medications in the country, providing coverage to Medicare beneficiaries and the disabled. Although Part D is sponsored by the Centers for Medicare & Medicaid Services (CMS), it is administered by health plans that have the ability to implement restrictions on medication use in the form of drug benefit. Evidence generated from previous studies demonstrate that formulary controls can impact patients'' medication-taking behavior and, ultimately, patient outcomes.4 However, conclusions drawn from these studies were largely based on populations that included nonelderly, commercial, or non-US populations.4 Elderly people could behave differently from younger people in response to formulary controls, given their increased likelihood of comorbidities and greater need for medications to maintain good health.No study to date has collated existing data to assess the consistency in the findings regarding the impact of formulary controls on medication use—defined in this current study as adherence, change in days supply, medication fills, and number of tablets—in the elderly. Synthesizing evidence from previous studies involving elderly populations may help in assisting Medicare and other health plan benefit design guidelines in the future.Therefore, the objective of this study was to summarize the effects of formulary controls on the US elderly (ie, Medicare) population based on previously published studies to generate evidence using earlier research that could be used to make future coverage decisions. Formulary controls included all formulary strategies that use mechanisms such as formulary restrictions and benefit design, including tiered copayments, step edits, prior authorization, and generic substitution.     

Hematologic Complications,Healthcare Utilization,and Costs in Commercially Insured Patients with Myelodysplastic Syndrome Receiving Supportive Care

Background

Myelodysplastic syndrome (MDS) is rare in people aged <50 years. Most patients with this disorder experience progressive worsening of blood cytopenias, with an increasing need for transfusion. The more advanced and severe the disorder, the greater the risk that it will progress to acute myeloid leukemia. Therapy is typically based on the patient''s risk category, age, and performance status. Supportive care alone is a major option for lower-risk, older patients with MDS or those with comorbidities. The only potentially curative treatment option is hematopoietic stem-cell transplantation, which is typically used to treat high-risk, younger patients.

Objective

To describe and compare the hematologic complications, healthcare utilization, and costs of supportive care in patients with MDS aged <50 years and in older patients aged ≥50 years.

Methods

Using the i3/Ingenix LabRx claims database, this retrospective study included patients who were continuously enrolled (ie, 6 months preindex through 1 year postindex) in the study and who had an initial claim of MDS (index date) between February 1, 2007, and July 31, 2008. Patients treated with hypomethylating agents or thalidomide analogues were excluded. Claims included information on office visits, medical procedures, hospitalizations, drug use, and tests performed. The hematologic complications, costs, and utilization analyses were stratified by age into 2 age-groups—patients aged <50 years and those aged ≥50 years. The MDS-related diagnoses, utilization, and costs were analyzed postindex. The data used in this study spanned the period from August 1, 2006, to July 31, 2009.

Results

We identified 1133 newly diagnosed patients with MDS who received supportive care only during the study period; of these, 19.5% were younger than age 50 years. These younger patients included more females (62.0% vs 52.5%; P = .011) and had fewer comorbidities (mean Charlson comorbidy index, 1.2 vs 2.4; P <.001) and physician office visits than those aged ≥50 years. Postindex, compared with the older patients, the younger patients had less use of erythropoietin therapy and fewer transfusions, anemia diagnoses, and potential complications of neutropenia and pneumonia diagnoses; however, more diagnoses of neutropenia and of decreased white blood cell counts were seen in the younger patients than in the older patients (P ≤.034 for all comparisons). Furthermore, younger patients had fewer mean office visits in the postindex period than older patients (17.5 vs 24.2, respectively; P <.001) and fewer hospitalizations (32.1% vs 44.6%, respectively; P = .004), but they had a longer (although not statistically significant) mean length of hospital stay (21 vs 14 days, respectively; P = .131). Mean total healthcare charges were $96,277 (median, $21,287) in younger patients compared with $84,102 (median, $39,402) in older patients, although this difference, too, was not significant.

Conclusions

MDS is associated with frequent and prolonged hospitalizations, frequent outpatient visits, and high costs in younger and in older patients who are receiving supportive care. Although this study shows that younger patients aged <50 years do not have significantly higher costs overall, a small proportion may have a higher healthcare utilization and cost-related burden of MDS than patients aged ≥50 years.Myelodysplastic syndrome (MDS) encompasses a heterogeneous group of clonal disorders of hematopoiesis and is characterized by dysplastic morphology of marrow and blood cells, ineffective hematopoiesis, and peripheral blood cytopenias.1,2 Most patients with MDS experience progressive worsening of blood cytopenias, with an increasing need for transfusion.2 These patients also have an increasing number of potentially fatal infections and hemorrhagic complications.2 The more advanced and severe the MDS is, the greater the risk that the disease will progress to acute myeloid leukemia (AML).3 The disease may be classified into 1 of 5 subtypes—refractory anemia, refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess of blasts (RAEB), RAEB in transformation (RAEB-T), or chronic myelomonocytic leukemia.3 Approximately 5% to 15% of the relatively lower-risk patients with refractory anemia/RARS transform to AML; by contrast, 40% to 50% of the high-risk patients with RAEB/RAEB-T transform to AML.3The therapeutic options that are tailored for specific MDS subgroups are typically based on factors such as the patient''s risk category, age, and performance status.3,4 The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recommend that all patients with MDS receive supportive care,3 which includes blood transfusions, erythropoietin with or without granulocyte colony-stimulating factor, iron chelation therapy, and prophylactic antibiotics.4,5 Other therapies indicated for the treatment of patients with MDS include the thalidomide analogue lenalidomide and the hypomethylating agents decitabine and 5-azacytidine.3,4 The only potentially curative treatment option is hematopoietic stem-cell transplantation, which is typically used to treat younger, high-risk patients.3,4 Supportive care alone remains a leading option for the treatment of lower-risk, older patients with MDS or those with comorbidities.3,4Data on the distribution of MDS in the general population are inconsistent, possibly because of misdiagnoses and/or underreporting of the disease.6,7 The most recent estimates of the annual incidence of MDS in the United States range from 3.3 to 5.0 per 100,000 persons.3,7,8 Some studies indicate that the median age of patients with MDS is approximately 65 years, whereas others note that more than 70% of cases occur in patients aged ≥70 years in the United States.3,6,9 The incidence of MDS in individuals aged ≥70 years is between 22 and 45 per 100,000 persons and increases with age.3,6,9–11Less than 10% of patients with MDS are aged <50 years; therefore, little is known about this disease in this younger age-group, particularly among patients who receive supportive care only.6,11,12 Some data suggest that younger patients with MDS have less aggressive disease.12,13 We compared hematologic complications, healthcare utilization, and costs in patients aged <50 years and in those aged ≥50 years who were newly diagnosed with MDS and received supportive care only.

KEY POINTS

• ▸ The more advanced and severe the myelodysplastic syndrome (MDS) is, the greater the risk of progression to acute myeloid leukemia. Therapy is currently based on risk category, age, and performance status.
• ▸ In the United States, the majority of newly diagnosed patients with MDS receive only supportive care, although for younger patients at high-risk, hematopoietic stem-cell transplantation is potentially the only curative option.
• ▸ This analysis compares the hematologic complications, healthcare utilization, and cost of care between patients with MDS aged <50 years and those aged ≥50 years who receive supportive care only.
• ▸ Although the younger patients had fewer office visits, they had longer mean length of hospital stay than the older group (21 vs 14 days, respectively).
• ▸ Mean total healthcare charges were $96,277 in younger patients compared with $84,102 in older patients.
• ▸ Based on this study, approximately 20% of patients with MDS are under age 50 years.
• ▸ The results of this study suggest that a small proportion of younger patients with MDS who receive supportive care only may have a higher healthcare utilization and cost-related burden of MDS than older patients with this condition.

     

Modeling the Frequency and Costs Associated with Postsurgical Gastrointestinal Adverse Events for Tapentadol IR versus Oxycodone IR

Background

Few studies have estimated the economic effect of using an opioid that is associated with lower rates of gastrointestinal (GI) adverse events (AEs) than another opioid for postsurgical pain.

Objective

To estimate the number of postsurgical GI events and incremental hospital costs, including potential savings, associated with lower GI AE rates, for tapentadol immediate release (IR) versus oxycodone IR, using a literature-based calculator.

Methods

An electronic spreadsheet–based cost calculator was developed to estimate the total number of GI AEs (ie, nausea, vomiting, or constipation) and incremental costs to a hospital when using tapentadol IR 100 mg versus oxycodone IR 15 mg, in a hypothetical cohort of 1500 hospitalized patients requiring short-acting opioids for postsurgical pain. Data inputs were chosen from recently published, well-designed studies, including GI AE rates from a previously published phase 3 clinical trial of postsurgical patients who received these 2 opioids; GI event–related incremental length of stay from a large US hospital database; drug costs using wholesale acquisition costs in 2011 US dollars; and average hospitalization cost from the 2009 Healthcare Cost and Utilization Project database. The base case assumed that 5% (chosen as a conservative estimate) of patients admitted to the hospital would shift from oxycodone IR to tapentadol IR.

Results

In this hypothetical cohort of 1500 hospitalized patients, replacing 5% of oxycodone IR 15-mg use with tapentadol IR 100-mg use predicted reductions in the total number of GI events from 1095 to 1085, and in the total cost of GI AEs from $2,978,400 to $2,949,840. This cost reduction translates to a net savings of $22,922 after factoring in drug cost. For individual GI events, the net savings were $26,491 for nausea; $12,212 for vomiting; and $7187 for constipation.

Conclusion

Using tapentadol IR in place of a traditional μ-opioid shows the potential for reduced GI events and subsequent cost-savings in the postsurgical hospital setting. In the absence of sufficient real-world data, this literature-based cost calculator may assist hospital Pharmacy & Therapeutics committees in their evaluation of the costs of opioid-related GI events.Pain is a global health problem that affects 1 of 5 adults in the community1 and occurs in 43% to 77%2–4 of the approximate 35.1 million patients who are hospitalized annually in the United States.5 Pain is ubiquitous among the nearly 30.2 million people who undergo inpatient surgery annually in the United States.5 Opioid analgesics are a mainstay of postsurgical pain management,6 but are often associated with treatment-limiting gastrointestinal (GI), central nervous system, and respiratory adverse events (AEs).7 Of these, opioid-related GI AEs are the most common,8–10 with an incidence rate of 10% to 32% for nausea and/or vomiting and 15% to 41% for constipation.7,11–14 These GI AEs are particularly troublesome after surgery, because they can exacerbate anesthesia-induced nausea and decreased GI motility, sometimes resulting in ileus.7 Furthermore, GI AEs are associated with increased healthcare resource utilization because of additional medications used to manage the GI AEs and an increase in hospital length of stay (LOS).7,10,15–17

KEY POINTS

• ▸ Opioid analgesics, a key to postsurgical pain management, are associated with lower gastrointestinal (GI) and other adverse event rates.
• ▸ Unlike traditional opioids, such as oxycodone IR, that exert analgesic activity by binding to μ-opioid receptors, tapentadol IR has a second mechanism involving norepinephrine reuptake inhibition, which may help to minimize GI events.
• ▸ Previous studies have shown that tapentadol IR causes fewer GI events than oxycodone IR in the postsurgical setting.
• ▸ This new study compared the total GI events and associated incremental costs for tapentadol IR versus oxycodone IR in the postsurgical setting from a hospital perspective, using a cost calculator and a hypothetical cohort of 1500 hospitalized patients requiring short-acting opioids.
• ▸ Replacing 5% of oxycodone IR 15-mg use with tapentadol IR 100 mg reduced the total number of postsurgical GI events from 1095 to 1085, which was associated with a cost reduction from $2,978,400 to $2,949,840.
• ▸ Individual GI event net savings for the 5% use of tapentadol IR instead of oxycodone IR were $26,491 for nausea, $12,212 for vomiting, and $7187 for constipation.
• ▸ The potential cost-savings associated with reduced GI events seen with tapentadol IR versus oxycodone IR in the postsurgical setting may suggest the need to look beyond drug-acquisition cost to consider the effect on net costs of care when making formulary decisions.

The guidelines for managing surgery-related pain advocate a multimodal, opioid-sparing approach to improve analgesic activity and to minimize the risk for opioid-related AEs.6,18 Most traditional opioids exert analgesic activity by binding to μ-opioid receptors in the brain; these receptors are also present in the GI tract. Tapentadol is a centrally acting analgesic with 2 mechanisms of action—μ-opioid receptor agonism and norepinephrine reuptake inhibition.19,20 These 2 mechanisms of action may account for the significant analgesia, along with the lower incidence and intensity of AEs that are normally associated with traditional μ-opioid receptor agonists, such as oxycodone.21In 2 phase 3 studies of patients with acute pain, including postoperative pain, the incidence of GI AEs was lower with tapentadol immediate release (IR) than with oxycodone IR at equianalgesic doses, including dose strengths other than tapentadol IR 100 mg.22,23We chose oxycodone IR as the traditional opioid because of its inclusion in guidelines for surgery-related pain,6 the availability of pivotal clinical studies comparing oxycodone IR with tapentadol IR,23,24 and its spectrum of AEs that is similar to that of tapentadol IR.23,24Although the clinical benefits of using opioids with different mechanisms of action are well documented, few studies have examined the potential economic effect of this strategy in postsurgical populations.The objective of this study was to estimate the number of potential reductions in postsurgical GI AEs and incremental hospital costs for GI event rates associated with tapentadol IR versus oxycodone IR, using a literature-based calculator. The analysis focused on data related to postsurgical GI AE rates, because of their availability in the published literature.     

The Impact of 5-HT3RA Use on Cost and Utilization in Patients with Chemotherapy-Induced Nausea and Vomiting: Systematic Review of the Literature

Background

Individual studies have assessed the impact of standard prophylactic therapy with 5-hydroxytryptamine receptor antagonists (5-HT₃RAs) for chemotherapy-induced nausea and vomiting (CINV) on cost and utilization, but no synthesis of the findings exists.

Objective

To systematically review published literature on costs and utilization associated with CINV prophylaxis with palonosetron and other 5-HT₃RAs.

Methods

PubMed and the National Institute for Health Research Centre for Reviews and Dissemination databases, conferences of 4 organizations (ie, Academy of Managed Care Pharmacy, American Society of Clinical Oncology, International Society for Pharmacoeconomics and Outcomes Research, and Multinational Association of Supportive Care in Cancer), and the bibliographies of relevant articles were queried for the medical subject headings and key terms of “ondansetron,” “granisetron,” “palonosetron,” “dolasetron mesylate,” “costs,” “cost analysis,” and “economics.” We included records published (full-length articles after 1997 and conference presentations after 2010) in English and with human patients, reporting data on cost and utilization (rescue medication, outpatient and inpatient services) associated with the use of 5-HT₃RAs for the treatment or prevention of CINV.

Results

Of the 434 identified studies, 32 are included in the current analysis: 7 studies report costs, 18 report utilization, and 7 studies report both. The costs are reported in US dollars (7 studies), in Euros (5 studies), and in Canadian dollars (2 studies). The studies vary in designs, patients, 5-HT₃RA regimens, and the definition of outcomes. The US studies report higher drug costs for CINV prophylaxis with palonosetron compared with ondansetron, lower medical outpatient and inpatient costs for palonosetron versus other 5-HT₃RAs, and higher acquisition costs for palonosetron versus ondansetron or other 5-HT₃RAs. Fewer patients receiving palonosetron versus with ondansetron or other 5-HT₃RAs required rescue medication or used outpatient or inpatient care. In Europe and in Canada, the total pharmacy costs and use of rescue medications reported are lower for patients receiving prophylaxis with palonosetron.

Conclusions

This analysis shows that prophylaxis with palonosetron for the treatment of CINV is associated with higher acquisition treatment costs, but also with lower use of rescue medications and outpatient and inpatient services compared with ondansetron or other 5-HT₃RAs in the United States. Therefore, the use of palonosetron as a standard treatment may lead to reduced service utilization for CINV.Chemotherapy-induced nausea and vomiting (CINV) is an adverse effect of cancer treatment. It may occur within a few minutes of or up to 24 hours after the administration of chemotherapy (ie, acute CINV), or it may occur more than 24 hours after treatment (ie, delayed CINV). CINV may last up to 7 days.1–7Although there are several patient-specific factors that place patients at an increased risk for developing CINV (eg, female sex, low consumption of alcohol, history of motion or morning sickness, age under 50 years, previous CINV), the most contributory risk factor is the emetogenic potential of the chemotherapy regimen itself.8

KEY POINTS

• ▸ Poorly controlled CINV may lead to nutrient depletion, reduced functional ability, diminished quality of life, or the premature discontinuation of chemotherapy.
• ▸ Previous studies have examined the impact of CINV prophylaxis with palonosetron and other 5-HT₃RAs on cost and utilization, but this is the first systematic review of the published literature on this topic.
• ▸ A total of 32 studies were included in this systematic literature review, of which 14 studies report costs and 25 reported utilization.
• ▸ This review indicates that palonosetron is associated with higher treatment costs but also with lower rescue medication use and outpatient and inpatient services use compared with other 5-HT₃RAs.
• ▸ Based on this analysis, the use of palonosetron as a standard treatment may lead to reduced service utilization for CINV.

More than 90% of patients undergoing highly emetogenic chemotherapy (HEC) will experience emesis without antiemetic prophylaxis, and 30% to 90% of those undergoing moderately emetogenic chemotherapy (MEC) will vomit without the prophylactic administration of antiemetics.8 From 10% to 30% of the patients receiving low emetogenic risk chemotherapy (LEC), and <10% of patients receiving minimal emetogenic risk chemotherapy (MinEC), will experience emesis without the administration of antiemetics.3,6,7,9 The dose, frequency, and length of administration, as well as the combination of agents may impact the emetogenicity of the chemotherapy.7Poorly controlled CINV may lead to nutrient depletion, reduced functional ability, diminished quality of life, or the premature discontinuation of chemotherapy.1-4,6,7,9 The use of prophylactic antiemetic medications in patients undergoing HEC may reduce the incidence of CINV to as low as 30%.7 A multidrug regimen containing a 5-hydroxytryptamine receptor antagonist (5-HT₃RA) is the standard approach for CINV prophylaxis.7 Drugs in this category include dolasetron mesylate, granisetron, ondansetron, palonosetron, and tropisetron, with palonosetron recommended as the preferred 5-HT₃RA for CINV prophylaxis with MEC by the guidelines of the National Comprehensive Cancer Network (NCCN), the Multinational Association of Supportive Care in Cancer/Economic Society for Medical Oncology (MASCC/ESMO), and the American Society of Clinical Oncology (ASCO).5,7,10Secondary rescue medications are used to treat breakthrough CINV among patients who have received prophylaxis.7 These medications may include metoclopramide, lorazepam, diphenhydramine, olanzapine, prochlorperazine, or dexamethasone.CINV increases direct costs (eg, medication, office visits, or hospitalizations) and indirect costs (eg, missed work).3,4,9 The effective prevention of CINV may reduce these costs. The clinical and economic impact of CINV underscore the importance of achieving CINV prophylaxis.3,4,9 Palonosetron—which has greater binding affinity and a longer half-life than the other 5-HT₃RAs, binds allosterically, stimulates receptor internalization, demonstrates positive cooperativity, and cross talks with the neurokinin (NK)-1 signaling pathway—prevents both acute and delayed CINV more effectively than the other 5-HT₃RAs.7,11-14The extent to which the clinical benefit of 5-HT₃RAs translates into reduced costs or utilization of healthcare services among patients with CINV has been shown in individual studies for subsets of outcomes,3,15 but no summary of the literature exists. We conducted a systematic literature review of published research on the healthcare costs and utilization associated with the use of 5-HT₃RAs for the prevention of CINV in patients receiving chemotherapy, with the goal of comparing palonosetron with the other 5-HT₃RAs.     

Patient Preferences and Treatment Adherence Among Women Diagnosed with Metastatic Breast Cancer

Background

Given the various profiles (eg, oral vs intravenous administration, risk of hot flashes vs fatigue) of treatment options (eg, endocrine therapy, chemotherapy) for metastatic breast cancer (mBC), how patients value these attributes of their medications has implications on making treatment decisions and on adherence.

Objectives

To understand how patients trade off medication side effects with improved effectiveness and/or quality of life, to provide estimates of nonadherence among women with mBC, and to quantify the association of medication nonadherence with health outcomes.

Methods

The study was a cross-sectional, Internet-based survey of 181 women diagnosed with mBC who were recruited from cancer-specific online panels (response rate, 7%). Treatment information, demographics, nonadherent behaviors, and quality of life assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) were collected in the survey, and each respondent completed a choice-based conjoint exercise to assess patient preferences. The patients'' preferences were analyzed using hierarchical Bayesian logistic regression models, and the association between the number of nonadherent behaviors and the health outcomes was analyzed using general linear models.

Results

The mean age of the patient sample was 52.2 years (standard deviation, ±9.1), with 93.9% of participants being non-Hispanic white. Results from the conjoint model indicated that effectiveness (overall survival) was of primary importance to patients, followed by side effects—notably alopecia, fatigue, neutropenia, motor neuropathy, and nausea/vomiting—and finally, dosing regimen. In all, 34.8% of survey respondents either discontinued their treatment or were nonadherent to their treatment regimen. Among those who have ever used oral chemotherapy (N = 95; 52.5%) and those currently using oral chemotherapy (N = 44; 24.3%), the number of nonadherent behaviors was significantly associated with a decrease in functional well-being (b [unstandardized regression coefficient] = −2.01 for patients who had ever used a targeted therapy and b = −3.14 for current users of a targeted therapy), FACT-General total score (b = −4.30 and b = −7.37, respectively), FACT-B total score (b = −3.93 and b = −6.11, respectively), and FACT trial outcome index (b = −5.22 and b = −8.63, respectively; all P <.05).

Conclusions

Patients were willing to accept substantial additional risks from side effects for gains in overall survival. Approximately 33% of women with mBC reported engaging in nonadherent behaviors. Because forgetfulness and adverse events were among the most frequent reasons for nonadherence, these results suggest that less complex treatment regimens, as well as regimens with less toxic profiles, may be associated with improvements in adherence and, subsequently, could correspond to perceptible patient benefits.Breast cancer is the most common cancer diagnosed among women in the United States, with an estimated 232,000 new cases diagnosed annually.1 It is also the second most deadly cancer, accounting for nearly 40,000 deaths annually.1 The 5-year survival rates for early-stage breast cancer is between 84% for regional disease (ie, contained within the breast and lymph nodes) and 99% for localized disease (ie, contained within the breast); the survival rate drops to 24% in more advanced stages of the disease.2 Metastatic breast cancer (mBC) is defined as breast cancer that has spread to other parts of the body. Whereas less than 10% of women are initially diagnosed with mBC, approximately 33% of women who are treated for early-stage disease will progress to mBC.2,3 The majority of breast cancer metastases affect the lymph nodes, followed by bone, liver, and lung.4,5At present, mBC is incurable, and treatment is focused on arresting the disease and extending patient survival, as well as promoting quality of life (QOL) and ensuring adequate symptom management.3,4 Treatment strategies may include endocrine therapy (eg, exemestane); targeted therapies, such as anti-HER2 agents (eg, trastuzumab); and chemotherapy (eg, capecitabine).6 As a result of the currently incurable nature of mBC and the side-effect profile associated with various forms of therapy, investigators have explored the potential role of patient preferences in decision-making regarding their treatment goals and desired outcomes.7–11 For example, aggressive treatment may maximize the duration of survival but may also be associated with significant and burdensome side effects that impair QOL.3,4Using the responses of 102 patients with breast cancer, Beusterien and colleagues recently revealed distinct preferences across side-effect profiles and a willingness to undergo more difficult treatment regimens to reduce the risk of more severe symptoms.7 Moreover, another study of 121 patients with breast cancer demonstrated the importance of a relatively minor survival benefit (as little as 3 months) for the perceived value of chemotherapy among patients with breast cancer, despite an increased risk for treatment toxicities.8 Further studies have shown a willingness of patients to trade a minor increase in disease recurrence risk for more convenient treatment regimens,9 as well as examining patient preferences for follow-up care10 and the ability for preferences to predict the eventual use of chemotherapy.11To our knowledge, no study to date has examined patient preferences using a conjoint method in women with mBC. In part, this may be because it is difficult to recruit this patient population for research survey purposes. Several studies have been conducted that have focused on patients diagnosed with early-stage breast cancer.12,13 McQuellon and colleagues surveyed women diagnosed with early-stage disease to assess their preferences for the hypothetical treatment of mBC.14 Although there was a wide range of preference profiles among the women who were surveyed, they were once again consistently willing to trade the risk of major side effects and toxicities for a modest survival benefit.14 However, because that study was initiated nearly 20 years ago, treatment advances since the time of that study were not included in that analysis.The primary objective of the current study is to provide an examination of contemporary treatments and to provide data on the treatment preferences of women with mBC to understand how these patients trade off side effects with increases in effectiveness and/or QOL.Patient preferences may have implications not only for treatment decision-making but also potentially for treatment adherence and follow-up care.15 If patient preferences and prescribed treatment regimens are misaligned, women diagnosed with breast cancer may become nonadherent, which could have implications for symptom management and for survival.15 To date, much of the research in this domain has focused on adherence to adjuvant therapy in patients with early-stage disease.16–18 A secondary objective of this study is to provide real-world evidence of nonadherence among women with mBC and to quantify the association with nonadherent behavior and health outcomes. We focused on adherence among patients receiving oral chemotherapy, because these agents are increasing in availability, and they represent a frequently self-administered treatment (as opposed to intravenous treatment, which is often not self-administered), and are thus more susceptible to nonadherent behaviors.

KEY POINTS

• ▸ Metastatic breast cancer (mBC) involves various drug regimens with different efficacy and side-effect profiles that may affect medication adherence.
• ▸ This is the first study to examine patient preferences in women with mBC.
• ▸ Of the 181 women with mBC surveyed, approximately 33% were nonadherent to their treatment regimen.
• ▸ Patients receiving hormone therapy reported the greatest nonadherence, followed by patients receiving an oral chemotherapeutic agent.
• ▸ Across all treatment modalities, forgetfulness (41.3%) and intolerance of side effects (36.5%) were the most common reasons for nonadherence.
• ▸ Although it is more convenient, women receiving oral chemotherapy were more likely to have significant declines in their health status.
• ▸ Patients are willing to trade substantial side-effect risks for gains in overall survival.
• ▸ The most important attributes of treatments were effectiveness and side effects; cost-related concerns were listed as the least important.
• ▸ The survey suggests that less complex and less toxic regimens may improve medication adherence and, ultimately, health outcomes.