Minimal important differences in the Migraine-Specific Quality of Life Questionnaire (MSQ) version.

To propose minimal important differences (MID) for the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1). To our knowledge (to date), no published MID values exist for the MSQ v2.1 in any population. Analyses were performed on data from two pivotal clinical trials of topiramate for migraine prevention (n = 916), as well as from the QualityMetric National Headache Survey (n = 1016). Analyses included both distribution- and anchor-based MID techniques as well as group- and individual-level MID values. Group-level anchor-based MID values ranged from 3.2 [Role Restrictive domain (RR)] to 7.5 [Emotional Functioning domain (EF)], setting the minimum level of appropriate MID (which can also aid with power analysis). Individual-level distribution-based MID values resulted in highly similar estimates from two large databases: median MID of 8.5 for RR, 9.2 for Role Preventive (RP) and 12.0 for EF. Finally, individual-level anchor-based MID values ranged from 5.0 (RR and RP domains) to 10.6 (EF). For group-level purposes of calculating power for future studies, an MID of 3.2, 4.6 and 7.5 for RR, RP and EF is recommended. For within-group analyses for analysing clinical trial efficacy of each patient's change with responder analyses, 5 points is necessary for RR. For RP and EF, ranges are recommended: 5.0 to 7.9 for RP and 8.0 to 10.6 for EF. These latter two domains tend to have more error in the MID, and thus a sensitivity analysis with both ends of the range should be used to confirm significant differences in responder analyses.

The risks and costs of multiple-generic substitution of topiramate.

OBJECTIVE: To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ). METHODS: Medical and pharmacy claims data of Régie de l'Assurance-Maladie du Québec from January 2006 to October 2007 were used. Patients with epilepsy treated with topiramate were selected. An open-cohort design was used to classify the observation period into periods of brand, single-generic, and multiple-generic use. One-year generic-switch and switchback-to-brand rates were estimated using Kaplan-Meier methodology. Medical resource utilization and costs were compared among the three periods using multivariate regression analysis. RESULTS: In total, 948 patients were observed during 1,105 person-years of brand use, 233 person-years of single-generic use, and 92 person-years of multiple-generic use. A total of 23% of generic users received at least two different generic versions. Compared to brand use, multiple-generic use was associated with higher utilization of other prescription drugs (incidence rate ratio [IRR] = 1.27, 95% confidence interval [CI] = 1.24-1.31), higher hospitalization rates (0.48 vs 0.83 visit/person-year, IRR = 1.65, 95% CI = 1.28-2.13), and longer hospital stays (2.6 vs 3.9 days/person-year, IRR = 1.43, 95% CI = 1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: IRR = 1.08, 95% CI = 0.88-1.34, length of stay: IRR = 1.12, 95% CI = 1.03-1.23). The risk of head injury or fracture was nearly three times higher (hazard ratio = 2.84, 95% CI = 1.24-6.48) following a generic-to-generic switch compared to brand use. The total annualized health care cost per patient was higher in the multiple-generic than brand periods by C$1,716 (cost ratio = 1.21, p = 0.0420). CONCLUSION: Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Quantifying the population impact of a prophylactic Helicobacter pylori vaccine.

BACKGROUND: Helicobacter pylori vaccines, which have been suggested as promising interventions to control infection, are under development. We sought to quantify the potential population impact of a prophylactic H. pylori vaccine. METHODS: We developed a mathematical model that compartmentalized the population according to age, infection status and clinical state. A proportion of individuals was assumed to acquire infection and develop gastritis, duodenal ulcer (DU), chronic atrophic gastritis and gastric cancer (GC). We first simulated the model without vaccine intervention, to obtain estimates of H. pylori prevalence, and GC and DU incidences based on intrinsic dynamics. We then incorporated a prophylactic vaccine (80% efficacy, lifetime protection, 80% coverage) targeting all infants. We tested vaccination programs over unlimited as well as limited time spans. Analyses were performed for the US, Japan and a prototypical developing country. RESULTS: In the US, our model predicted a decrease in H. pylori prevalence from 12.0% in 2010 to 4.2% in 2100 without intervention. With 10 years of vaccination beginning in 2010, prevalence would decrease to 0.7% by year 2100. In the same period, incidence of H. pylori-attributable GC would decrease from 4.5 to 0.4 per 100,000 with vaccine (compared to 1.3 per 100,000 without vaccine). Incidence of H. pylori-attributable DU would decrease from 33.3 to 2.5 per 100,000 with vaccine (compared to 12.2 per 100,000 without vaccine). In Japan, incidence of H. pylori-attributable GC would decrease from 17.6 to 1.0 per 100,000 after 10 years of vaccination (compared to 3.0 per 100,000 without vaccine). In a prototypical developing country, after 10 years of vaccination, H. pylori-attributable GC would decrease from 31.8 to 22.5 per 100,000 by 2090, returning to the original level by mid-2100s. Under continuous vaccination, it would decrease to 5.8 per 100,000 by 2100. INTERPRETATION: In the US and Japan, a 10-year vaccination program would confer almost the same reduction in H. pylori and associated diseases as a vaccination effort that extends beyond 10 years. In developing countries, a continuous vaccination effort would be required to eliminate the pathogen and its associated diseases.

A dynamic transmission model for predicting trends in Helicobacter pylori and associated diseases in the United States.

To assess the benefits of intervention programs against Helicobacter pylori infection, we estimated the baseline curves of its incidence and prevalence. We developed a mathematical (compartmental) model of the intrinsic dynamics of H. pylori, which represents the natural history of infection and disease progression. Our model divided the population according to age, infection status, and clinical state. Case-patients were followed from birth to death. A proportion of the population acquired H. pylori infection and became ill with gastritis, duodenal ulcer, chronic atrophic gastritis, or gastric cancer. We simulated the change in transmissibility consistent with the incidence of gastric cancer and duodenal ulcer over time, as well as current H. pylori prevalence. In the United States, transmissibility of H. pylori has decreased to values so low that, should this trend continue, the organism will disappear from the population without targeted intervention; this process, however, will take more than a century.

Helicobacter pylori vaccine development and use: a cost-effectiveness analysis using the Institute of Medicine Methodology.

BACKGROUND: Prophylactic vaccination has been suggested as a better strategy than antibiotics to control Helicobacter pylori infection. We evaluated the cost-effectiveness (CE) of H. pylori vaccine development and use in the United States and developing countries, using a method developed by the Institute of Medicine (IOM). METHODS: The IOM model includes costs of vaccine development, vaccination program, and averted medical treatments; morbidity and mortality prevented; expected efficacy and use; and proportion of disease that is vaccine-preventable. The model employs infant mortality equivalence (IME) to estimate disease burden; with IME, the societal cost of infection-related morbidity is expressed as equivalent to a specific rate of infant deaths. We tested model assumptions by univariate sensitivity analyses. RESULTS: In the United States, H. pylori vaccine would save 1,176 IME and would cost $58.71 million (1997 dollars) annually, yielding a CE ratio of $49,932 per IME; the health benefits would exceed all IOM-studied vaccines, even when efficacy dropped to 55%. H. pylori vaccine could be cost-saving if priced at less than $60 per course. In developing countries, H. pylori vaccine would rank unfavorably both in terms of health benefits (33,518 IME) and costs ($5,254 million). None of the changes in assumptions improved significantly the H. pylori vaccine's ranking relative to other IOM-studied vaccines. CONCLUSIONS: Compared to other vaccines evaluated in the IOM study, H. pylori vaccine warrants public resource allocation for accelerated development and use in the United States but not for use in developing countries.