Sheryl L. Szeinbach

Market withdrawal of new molecular entities approved in the United States from 1980 to 2009

Economic factors, market dynamics, and safety issues are largely responsible for decisions to withdraw pharmaceutical products from the market. In this study, new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) were examined in the USA from 1980 to 2009.

Incentives for orphan drug research and development in the United States

BackgroundThe Orphan Drug Act (1983) established several incentives to encourage the development of orphan drugs (ODs) to treat rare diseases and conditions. This study analyzed the characteristics of OD designations, approvals, sponsors, and evaluated the effective patent and market exclusivity life of orphan new molecular entities (NMEs) approved in the US between 1983 and 2007.MethodsPrimary data sources were the FDA Orange Book, the FDA Office of Orphan Drugs Development, and the US Patent and Trademark Office. Data included all orphan designations and approvals listed by the FDA and all NMEs approved by the FDA during the study period.ResultsThe FDA listed 1,793 orphan designations and 322 approvals between 1983 and 2007. Cancer was the main group of diseases targeted for orphan approvals. Eighty-three companies concentrated 67.7% of the total orphan NMEs approvals. The average time from orphan designation to FDA approval was 4.0 ± 3.3 years (mean ± standard deviation). The average maximum effective patent and market exclusivity life was 11.7 ± 5.0 years for orphan NME. OD market exclusivity increased the average maximum effective patent and market exclusivity life of ODs by 0.8 years.ConclusionPublic programs, federal regulations, and policies support orphan drugs R&D. Grants, research design support, FDA fee waivers, tax incentives, and orphan drug market exclusivity are the main incentives for orphan drug R&D. Although the 7-year orphan drug market exclusivity provision had a positive yet relatively modest overall effect on effective patent and market exclusivity life, economic incentives and public support mechanisms provide a platform for continued orphan drug development for a highly specialized market.

Using conjoint analysis to evaluate health state preferences

Quality of life dimensions are important considerations when patients evaluate pharmaceutical products with respect to personal benefits. Traditionally, standard gamble, time trade-off, and rating scale techniques are used to obtain preference (utility) estimates for various quality of life dimensions. This study examines three objectives to determine the feasibility of using conjoint analysis to elicit patient preferences for a particular health state. For the first objective, patients with multiple myeloma were asked to select quality of life conditions for 18 hypothetical patients with cancer and to indicate which conditions were the easiest and hardest to live with. Second, patients were asked to rate several cancer-related and general symptoms using visual analog scales. Third, comparisons were made between the two techniques to determine similarity and validity. Results revealed that conjoint analysis is useful for health-related quality of life research, and that conjoint analysis results compare favorably with values obtained from visual analog scales.

Precision and accuracy of commercial laboratories' ability to classify positive and/or negative allergen-specific IgE results

BACKGROUND Accurate and reliable evaluation of the presence or absence of allergen-specific IgE is important in the differential diagnosis of allergic disease. A variety of different commercial tests are available for this purpose. There are few data available to judge how the results of these different tests compare with one another in everyday use. OBJECTIVE To examine prospectively the extent of comparability among specific IgE results from different laboratories. METHODS Six diagnostic laboratories employing five different methods to assay specific IgE were selected. Aliquots from 26 serum samples that contained variable levels of IgE specific to 17 common aeroallergens were sent in triplicate to each study laboratory during a 6-week time period. Results were reported numerically and by class scores and then compared by examining their concordance using Kendalls W nonparametric statistical test. In addition, cut-off values were compared by a best agreement analysis using reported results. Reproducibility was determined using precision profiles based upon the coefficient of variation among triplicates for each allergen across the range of reported results. RESULTS In all, 7,813 tests were analyzed. Concordance among different assays in commercial use with one exception was not good. This was particularly true around the cut-off region where most assays demonstrated high imprecision. The Pharmacia CAP System used by two different laboratories demonstrated highly comparable results with good precision. Some assays were reproducible but not accurate. Others were neither reproducible nor accurate. CONCLUSIONS The results of this study indicate that not all commercial laboratories/assays for specific IgE provide reproducible and accurate data. Significant potential for misdiagnosis was detected for some reported results. Methods were identified that do give sensitive, accurate, and reproducible results.

Comparing Patient Preferences and Healthcare Provider Recommendations with the Pen Versus Vial-and-Syringe Insulin Delivery in Patients with Type 2 Diabetes

OBJECTIVES This study aimed to examine healthcare provider (HCP) recommendations and patient preferences for the insulin pen versus vial-and-syringe in patients with type 2 diabetes mellitus (T2DM) and to assess clinical end points and safety outcomes. SUBJECTS AND METHODS Using a randomized, open-label, crossover design, in total, 405 insulin-naive adults with T2DM from 60 centers received basal insulin glargine in one of two device treatment sequences (2 weeks of pen followed by 2 weeks of vial-and-syringe, or vice versa). The primary end point, patient device preference, was evaluated at Week 4 (end of the crossover period) using the Insulin Injection Preference Questionnaire. Patient preference and HCP recommendation were assessed with one global item and three subscale items (blood glucose control, reluctance to use insulin, and long-term insulin use) using a 5-point scale ranging from 1=not preferred or not recommended to 5=preferred or recommended. Patients were then re-randomized to either pen or vial-and-syringe for further observation (6, 10, and 30 weeks) to evaluate clinical end points (glycosylated hemoglobin [A1C] and fasting blood glucose levels) and safety outcomes (hypoglycemia and adverse events). RESULTS Patients reported a significant preference for pens over vial-and-syringe, and HCPs strongly recommended pens over vial-and-syringe (both P<0.001). Consistent response patterns were observed by HCPs and patients for the three subscale items. Fasting blood glucose, A1C levels, and the incidence of hypoglycemia were comparable in the two groups. CONCLUSIONS Patients preferred pens over vial-and-syringe, with the pen device also recommended by HCPs, when initiating basal insulin treatment in insulin-naive patients with T2DM.

Drug utilization and cost in a Medicaid population: A simulation study of community vs. mail order pharmacy

BackgroundOutpatient drugs are dispensed through both community and mail order pharmacies. There is no empirical evidence that substitution of community pharmacy with mail order reduces overall drug expenditures. The need for evaluating the potential effects on utilization and costs of the possible extension of mail order services in Medicaid provides the rationale for conducting this study. This study compares drug utilization and drug product cost in community vs. mail order pharmacy dispensing services in a Medicaid population.MethodsThis study is a retrospective cohort study comparing utilization and cost patterns in community vs. mail order pharmacy. A simulation model was employed to assess drug utilization and cost in mail order pharmacy using community pharmacy claim data. The model assumed that courses of drug therapy (CDT) in mail order pharmacy would have utilization patterns similar to those found in community pharmacy. A 95% confidence interval surrounding changes in average utilization and average cost were estimated using bootstrap analysis. A sensitivity analysis was performed by varying drug selection criteria and supply, fill point, and medication possession ratio (MPR). Sub-analyses were performed to address differences between mail order and community pharmacy related to therapeutic class and dual-eligible patients.Data for the study derived from pharmacy claims database of Ohio Medicaid State program for the period January 2000-September 2004. Drug claims were aggregated to obtain a set of CDTs representing unique patient IDs and unique drug products. Drug product cost estimates excluded dispensing fees and were used to estimate the cost reduction required in mail order to become cost neutral in comparison with community pharmacy.ResultsThe baseline model revealed that the use of mail order vs. community pharmacy would result in a 5.5% increase in drug utilization and a 5.4% cost reduction required in mail order to become cost neutral. Results from Ohio Medicaid drugs for chronic use revealed a 5.1% increase in utilization and a 4.9% cost reduction required to become cost neutral in comparison with community pharmacy.ConclusionThe results of the simulation model indicate that mail order pharmacy increases drug utilization and can also increase drug product cost if the cost per unit is not reduced accordingly. Prior consideration should be given to the patient population, day-supply, disease, therapy, and insurance characteristics to ensure the appropriate use of mail order pharmacy services.

The prevalence of pharmaceutical shortages in the United States

Shortages of drugs, vaccines, and other biologics are a perennial problem of the U.S. health care system. The objectives of this study were to assess the prevalence of these shortages of drugs, vaccines, and other biologics, and to characterize the products in short supply as reported in the United States by several public agencies and private organizations on June 1, 2011. Reported shortages of pharmaceuticals were obtained from the FDA, the CDC, the American Society of Health-System Pharmacists (ASHP), and the Brigham and Women’s Hospital (BWH). A list of approved drugs and licensed vaccines and other biologic products were obtained from the FDA. The units of analyses were the active ingredient(s) and the route of administration. The study included descriptive analyses of the characteristics of products experiencing shortages and an estimation of the prevalence of shortages as the proportion of non-discontinued FDA-approved products that were listed by the FDA in June 1, 2011. The most frequent characteristics of shortages included: reported by ASHP, referred to a drug approved under the NDA/ANDA system, contained only one active ingredient, was a drug administered by injection, required a prescription, was part of one of six main therapeutic classes, and was marketed by three or less companies. The overall prevalence of drug shortages was estimated at 11.0% of all the FDA-approved and marketed drugs, vaccines, and other biologics. Vaccines had the highest prevalence of shortage. The prevalence varied from 9.9% reported by the ASHP to 4.0% reported by public agencies and to 2.0% reported by BWH. Differences in the reporting of shortages can be attributed to variations in defining shortages and how they were characterized within each reporting organization. The highest prevalence rate was found among active ingredients with injection routes of administration (23.1%). Shortages are prevalent in the U.S. health care system. Several definitions of shortage are currently in use in the United States. Additional research is needed to develop a standard definition for a pharmaceutical shortage and to standardize the criteria used to characterize a pharmaceutical shortage.

Psychometric Development and Validation of the Chronic Constipation Treatment Satisfaction Questionnaire (CTSAT-Q)

OBJECTIVES To develop and validate the constipation treatment satisfaction questionnaire (CTSAT-Q) for use in patients with chronic constipation and irritable bowel syndrome with constipation (IBS-c). METHODS Questionnaire development included item representation from the reviewed literature, focus groups, and pretesting. Dimensions related to treatment satisfaction were identified with exploratory factor analysis, verified with confirmatory factor analysis (CFA), and tested with structural equation modeling. RESULTS A total of 31,988 email invitations were disseminated to obtain 311 qualified respondents with diagnoses for chronic constipation and IBS-c using ROME II criteria, which required that two of the following symptoms: fewer than 3 bowel movements per week, hard or lumpy stools, straining with defecation, and a sensation of incomplete evacuation, a sensation of anorectal obstruction, and the use of manual maneuvers to assist defecation be present 25% of the time during the last year. Approximately 84% of the sample was female. Item-to-total correlations were 0.66 for activities, ranged from 0.60 to 0.67 for expectations, from 0.59 to 0.69 for value, from 0.56 to 0.60 for effectiveness, and 0.68 to 0.79 for treatment satisfaction. All standardized parameter estimates from CFA were significant (P < 0.01). The chi-square was 46.98, df = 41, P = 0.241, comparative fit index = 0.996, Tucker-Lewis Index = 0.994, root mean square error of approximation = 0.022, indicating an excellent fit between the sample data and proposed model. Treatment satisfaction was a strong and significant predictor of effectiveness, activities, and value (P < 0.001). CONCLUSIONS The CTSAT-Q was demonstrated to be reliable and valid, and appears to assess treatment satisfaction for patients with chronic constipation and patients with IBS-c.

Evaluating catheter complications and outcomes in patients receiving home parenteral nutrition

RATIONALE, AIMS AND OBJECTIVES We describe catheter complications and outcomes in patients who received home parenteral nutrition (HPN) therapy. METHODS Retrospective chart data were obtained from Boston Home Infusion agency that provided HPN therapy to 212 patients [International Classification of Diseases, 9th revision (ICD-9) codes: gastrointestinal (GI)-related disorders and oncology] between 1 January 2005 and 30 September 2011. RESULTS Of the 163 patients who represented 19104 home-catheter days, 19 (11.7%) patients experienced 25 catheter complications (CCs; 12 occlusions, 11 central line-associated bloodstream infections, one thrombosis and one line dislodgment). The overall CC rate was 1.30 per 1000 peripherally inserted central catheter (PICC)-line days. The mean number of PICC-line days (278.7 ± 335.0 vs. 95.9 ± 154.0) and patients with at least one hospital admission were significantly higher for patients with one or more CCs compared with patients with no CCs (P<0.03). CONCLUSION Patients who experienced CCs had more PICC-line days, more hospital admissions and had an ICD-9 code for GI-related disorders compared with patients with oncology-related diagnoses.

Assessing the reliability and validity of a newly developed insomnia treatment satisfaction questionnaire (ITSAT-Q)

PURPOSE To produce a valid insomnia treatment satisfaction questionnaire (ITSAT-Q) to assess treatment satisfaction with pharmacotherapy for use in patients with insomnia. PATIENTS AND METHODS Items developed for a self-administered questionnaire were analyzed using exploratory factor analysis (EFA), which produced 5 dimensions. Confirmatory factor analysis was used to verify results from EFA, and structural equation modeling was used to test the hypothesized relationship among the dimensions. Data were collected from patients as part of a Sleep Research Project from January 2008 until October of 2008. RESULTS Approximately 69.8% of the sample (n=298) was female. Item-to-total correlations were 0.66 for convenience, ranged from 0.52 to 0.62 for expectations, from 0.54 to 0.69 for value, from 0.50 to 0.57 for effectiveness, and from 0.58 to 0.72 for treatment satisfaction. All standardized parameter estimates from confirmatory factor analysis were significant (p<0.01). Goodness of fit measures for the final structural equation model were chi(2)=45.2 (d.f.=45); p=0.465; CFI=1.00; TLI=1.00; and RMSEA=0.004. Treatment satisfaction was a strong and significant predictor of value, and effectiveness was a strong predictor of treatment satisfaction (p<0.01). Expectations were a strong and equal predictor of both treatment satisfaction and value (p<0.001). CONCLUSION The ITSAT-Q provided acceptable results for instrument reliability and validity. Findings from this study will provide additional insight regarding patient perceptions of treatment satisfaction and other related therapeutic dimensions to help prescribers assess pharmacotherapy.