Systematic Literature Review of the Methods Used to Compare Newer Second-Generation Agents for the Management of Schizophrenia: A focus on Health Technology Assessment.

BACKGROUND: The challenges of comparative effectiveness to support health technology assessment (HTA) agencies are important considerations in the choices of antipsychotic medications for the treatment of schizophrenia. OBJECTIVES: Our aim was to assess the study methods used and outcomes reported in the published literature to address the question of comparative effectiveness of newer antipsychotic agents and the adequacy and availability of evidence to support HTA agencies. DATA SOURCE: A systematic search of the PubMed database from 1 January 2009 to 30 September 2013 was conducted to identify studies evaluating new atypical antipsychotics reporting on comparative effectiveness. STUDY SELECTION: The systematic review comprised of studies on schizophrenia patients where at least two drugs were being compared and at least one treatment group received one of the following second-generation antipsychotics: risperidone, olanzapine, aripiprazole, paliperidone, asenapine, iloperidone, lurasidone, and quetiapine. The included studies were also required to have an efficacy, safety or economic outcome, such as Positive and Negative Syndrome Scale (PANSS) score, weight gain, resource utilization, or costs. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers (BW and GK) independently applied the inclusion criteria. Disagreements between reviewers were resolved by consensus, referring to the original sources. Information on the methodology and outcomes was collected for each included study. This included study description, head-to-head drug comparison, patient population, study methodology, statistical methods, reported outcomes, study support, and journal type. RESULTS: A total of 198 studies were identified from electronic search methods. The largest category of studies was randomized controlled trials [RCTs] (N = 73; 36.9%), which were largely directed at the regulatory endpoint. Fewer studies were undertaken for HTA-purposes cohort studies (N = 53; 26.8%), meta-analyses (N = 32; 16.2%), economic studies (N = 14; 7.1%), and cross-sectional studies (N = 13; 6.6%). Direct head-to-head comparisons preferred by HTA were dominated by the comparison involving olanzapine and risperidone, representing 149 (75.3%) and 119 (60.1%) studies, respectively. RCTs, which are the primary study type for regulatory submissions, showed a lack of bias. Studies aimed at HTA were not as well performed. Cohort studies suffered from bias in the selection of comparison groups, lack of control for confounders, and differential dropout rates. As a group, cross-sectional studies scored poorly for bias, with a primary failure to identify a representative sample. Economic studies showed highly variable bias, with bias in the representation of effectiveness data, model assumptions without validation, and lack of sensitivity analyses. LIMITATIONS: One limitation of this systematic review is that it only included studies from 2009 to 2013, potentially excluding some earlier comparator studies, particularly those involving first-generation antipsychotics. CONCLUSIONS: This review of comparative effectiveness studies of second-generation antipsychotic agents for schizophrenic patients revealed a wide range of study types, study methodologies, and outcomes. For traditional efficacy outcomes and select safety outcomes, there is strong evidence from many well-conducted studies; however, there are fewer studies of types preferred by HTA with limited head-to-head comparisons and a higher risk of bias in the execution of these studies.

Health-related quality of life in advanced prostate cancer and its treatments: biochemical failure and metastatic disease populations.

INTRODUCTION: This study aimed to examine the impact of advanced prostate cancer and its treatments on patients' perceptions of their health and to better understand concerns not captured by currently available health-related quality of life (HRQL) instruments. PATIENTS AND METHODS: Open ended one-on-one interviews were conducted with patients with prostate cancer who had biochemical failure or metastatic cancer to understand the impacts of disease and treatments on patients' perceptions of their lives. Interviews with 25 patients (7 biochemical failure and 18 metastatic) and 6 clinicians were conducted. Patient responses were analyzed to assess whether information saturation (ie, the point at which no new information is collected) was attained and compared with currently available HRQL instruments. The data informed the development of a comprehensive conceptual model illustrating the impacts of advanced disease and treatments. Clinical expert interviews also informed the conceptual model. RESULTS: Patients with prostate cancer reported many of the key symptoms already captured by current measures, such as bone pain, urinary functioning, bowel functioning, and fatigue. However, a number of impacts reported as bothersome by patients were identified that are not fully captured by existing HRQL measures. Specific examples include genital atrophy, muscle atrophy, stamina, body image, and emotional well-being. CONCLUSION: The conceptual model identified herein describes the impacts of prostate cancer and its treatments from the patient's perspective. The model can be useful in identifying key concepts important to patients that should be measured in trials to capture treatment benefits. The model also can help inform the selection of patient-reported outcomes to assess these benefits.

Administration costs of intravenous chemotherapy in treating peripheral T-cell lymphoma.

OBJECTIVE: This retrospective cohort analysis was conducted to examine the cost components of administering IV chemotherapy to peripheral T-cell lymphoma (PTCL) patients in the US to inform decision makers. METHODS: Patients diagnosed with PTCL (ICD-9 code 202.7X) between 1 October 2007 and 30 September 2012 were identified from a US administrative claims database. Costs for patients receiving at least one NCCN recommended IV chemotherapy were assessed using the allowed payment from claim line items, categorized into cost components (study drug costs, IV administration costs and other visit-related services). RESULTS: The mean costs to the payer for IV cancer therapy administration in a PTCL patient population averaged about $5735 per visit and $9356 per member per month (PMPM). Across all therapies, mean IV administration costs accounted for $127-$794 per visit and $594-$1808 PMPM, contributing an additional 2-32% to the total costs of the drug alone. Mean other visit-related services costs for treating PTCL accounted for $70-$2487 per visit and $444-$3094 PMPM, contributing an additional 2-74% to the total costs. Combined, these additional costs represent an additional mean cost of $220-$3150 per visit and $1193-$4609 PMPM to the base price of the drug alone. LIMITATIONS: This study used a convenience sample to identify PTCL patients and only included visits where at least one NCCN recommended IV chemotherapy was administered. CONCLUSIONS: The costs of IV administration and other visit-related services add measurable costs to the total cost of IV therapy for treating PTCL. When considering the cost of the drug, these additional costs can represent a substantial proportion of the overall costs and must be considered when evaluating the costs of IV treatment options for PTCL.

Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs.

OBJECTIVE: Nonadherence is a major challenge in schizophrenia treatment. While long-acting (depot) antipsychotic medications are often recommended to address adherence problems, evidence on the comparative effectiveness of depot versus oral antipsychotics is inconsistent. We hypothesize that this inconsistency could be due to systematic differences in study design. This review evaluates the effect of study design on the comparative effectiveness of antipsychotic formulations. The optimal use of different antipsychotic formulations in a general clinical setting depends on better understanding of the underlying reasons for differences in effectiveness across research designs. DATA SOURCES: A PubMed literature review targeted English-language studies (2000-2011) with information on relapse, hospitalization, or all-cause discontinuation for depot and oral antipsychotic treatment arms in schizophrenia. The time frame was chosen to reflect research focused on the newer generation of antipsychotic agents. The search required at least 1 term from each of the following categories: (1) schizophrenia; (2) inject, injection, injectable, injectables, injected, depot, long-acting; and (3) iloperidone, fluphenazine, haloperidol, paliperidone, risperidone, olanzapine, asenapine, flupentixol, flupenthixol, lurasidone, clopenthixol, fluspirilene, zuclopentixol, zuclopenthixol. STUDY SELECTION: Thirteen relevant studies were identified by 2 independent reviewers; these studies included information on 19 depot-oral comparisons. DATA EXTRACTION: Age- and gender-adjusted risk ratios (RRs) (depot/oral) were calculated for the identified endpoints and pooled by study design (randomized controlled trial [RCT], prospective observational, and retrospective observational). Meta-analysis with random effects was used to estimate the pooled RRs, by study design. Average conversion factors between study designs were calculated as the ratios of pooled RRs. RESULTS: Meta-analysis of adjusted endpoints showed no apparent benefit of depot over oral formulations in RCTs, with an RR of 0.89 (P = .416). In contrast, there was a significant advantage for depot formulations in other study designs (prospective RR = 0.62 [P < .001]; retrospective RR = 0.56 [P < .001]). These imply conversion factors of 1.43 and 1.59 between RCTs and prospective and retrospective designs, respectively. CONCLUSIONS: The comparative effectiveness of antipsychotic formulations is sensitive to research design. Depot formulations displayed significant advantages in nonrandomized observational studies, whereas in RCTs no difference was observed. The estimated conversion factors may facilitate comparison across studies.

Analysis of drug and administrative costs allowed by U.S. Private and public third-party payers for 3 intravenous biologic agents for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic condition with substantial morbidity that can now be treated with disease-modifying biologic agents that target tumor necrosis factor (TNF) or related mechanisms. The anti-TNF biologic agents are available in either intravenous (IV) or subcutaneous dose forms. The biologic agents with an indication for rheumatoid arthritis and administered only by IV infusion in medical offices include abatacept, infliximab, and rituximab. Although the literature on RA treatments, their outcomes, and aspects of their costs is substantial, the costs of administration by the IV route have not been directly studied. OBJECTIVE: To assess the detailed costs of administering IV biologic agents for the treatment of RA in relation to the total cost of the medication itself in the United States. METHODS: The sample included all patients with at least 1 medical claim with an ICD-9-CM diagnosis code for RA (codes 714.XX) in any claim field and at least 1 claim for infliximab, abatacept, or rituximab (HCPCS codes J1745, J0129, and J9310, respectively) at any time from January 1, 2006, through December 31, 2008, in a database associated with billing and claims administration for 72 U.S. medical clinics. Costs were determined using the payer allowed payment, which is the total contractual amount that the provider should receive, including the patient cost share. Costs were measured as the average cost per IV administration visit and in relation to the dose of medication billed. The authors verified that an RA diagnosis was present on 100% of infusion claims for the study drugs. RESULTS: Over the study period for claims with dates of service from January 1, 2006, through December 31, 2008, 72 medical clinics had claims for a total of 4,248 unique patients with RA and a total of 33,354 clinic visits in which these patients received at least 1 infusion of 1 of 3 biologic agents (26,586 for infliximab, 4,807 for abatacept, and 1,961 for rituximab). Mean (SD) total payment for all drugs and other cost components was $2,874 ($1,515) per visit, of which IV administration costs were $226 (7.9%); the mean cost of the biologic agent itself was $2,616 (91.0%), and other visit-related services were $33 (1.1%). For individual agents, the total costs of visits were $2,828, $1,827, and $6,076; and the costs of IV administration were $224, $171, and $390, respectively, for infliximab, abatacept, and rituximab. CONCLUSION: For patients who received an IV biologic agent to treat RA, IV administration costs accounted for 7.9% of the total cost of the visit.