Use of rituximab in adults with relapsing-remitting multiple sclerosis: a systematic literature review.

Objective: Rituximab is used as an off-label treatment for relapsing-remitting multiple sclerosis (RRMS); however, the comparative efficacy and safety of rituximab versus currently licensed disease-modifying drugs (DMDs) for RRMS is unknown. A systematic literature review was conducted to evaluate the available data pertaining to efficacy and safety of rituximab in adult patients with RRMS and highly active relapsing multiple sclerosis (HA-RMS); data quality was critically assessed via risk of bias (RoB) assessment.Methods: Biomedical literature databases were searched until mid-2018 and key proceedings were searched from 2016 to 2018. Critical appraisal of non-randomized studies was conducted using the Cochrane RoB assessment tool; randomized controlled trials (RCTs) were appraised using comprehensive assessment criteria based on the NICE guidelines.Results: Thirty-eight unique studies based on 49 publications were identified: 25 RRMS studies (one RCT) and 13 HA-RMS studies (no RCTs). The evidence among patients with RRMS generally favored rituximab in comparison to placebo (relapse rate) and interferons/glatiramer acetate (relapse rate and disability progression), although much of the non-randomized data were descriptive and/or not statistically significant. In comparison to placebo, rituximab was associated with a greater risk of adverse events. Two-thirds of the non-randomized RRMS studies were associated with critical/serious RoB; the single RCT was associated with low RoB. Furthermore, all of the non-randomized HA-RMS studies were associated with critical/serious RoB.Conclusions: Available evidence of off-label rituximab use for the treatment of patients with RRMS suggests generally favorable efficacy versus placebo and interferons/glatiramer acetate; however, the poor quality of the included studies limits any robust conclusions.

Health state utilities for infertility and subfertility.

BACKGROUND: Health state utility values allow for comparison of treatments across different diseases. Utility values for fertility-impaired health states are currently unavailable. Such values are necessary in order to determine the relative costs-effectiveness of fertility treatments. METHODS: This study aimed to determine utility weights for infertile and subfertile health states. In addition, it explored the Dutch general population's opinions regarding the inclusion of infertility treatments in the Dutch health insurers' basic benefit package. An online questionnaire was designed to determine the health-related quality of life values of six fertility-impaired health states. The study population consisted of a representative sample of the Dutch adult population. Respondents were asked to evaluate the health states through direct health valuation methods, i.e. the Visual Analogue Scale (VAS) and the Time Trade-Off (TTO) method. In addition, respondents were asked about their opinions regarding reimbursement of fertility-related treatments. RESULTS: The respondents' (n = 767) VAS scores ranged from 0.640 to 0.796. TTO utility values ranged from 0.792 to 0.868. Primary infertility and subfertility was valued lower than secondary infertility and subfertility. In total, 92% of the respondents stated that fertility treatments should be fully or partially reimbursed by the health insurance basic benefit package. CONCLUSIONS: Having fertility problems results in substantial disutilities according to the viewpoint of the Dutch general population. The results make it possible to compare the value for money of infertility treatment to that of treatments in other disease areas. There is strong support among the general population for reimbursing fertility treatments through the Dutch basic benefit package.

Estimating the implicit value of statistical life based on public interventions implemented in The Netherlands.

OBJECTIVES: In the Netherlands, allocation decisions have not yet been explicitly based on the Value of Statistical Life. However, when policy makers decide whether or not to implement life saving interventions this trade-off is made implicitly. This study aimed to gain insights into this trade-off, hereafter referred to as Implicit Value of Statistical Life (IVSL), by means of a retrospective investment analysis of life saving interventions implemented in the Netherlands. METHODS: A literature search was conducted to find life saving intervention cases meeting the requirements for IVSL calculation. A final sample of ten cases was included in the study concerning interventions implemented in different societal sectors. For each case, an IVSL estimate was calculated according to a uniform method. RESULTS: IVSL estimates derived from the intervention cases differed considerably and ranged from 1 euro to almost 11 million euros. Differences were most extreme when comparing IVSL estimates concerning interventions implemented in different societal sectors. However, IVSL estimates also varied greatly between interventions in the same sector and even within the same interventions when critical assumptions were altered. CONCLUSION: Our findings suggest that there are great imbalances between societal investments for preventing a statistical death. This highlights the need for further deliberation about how to improve transparency of policy decisions. An approach ex ante determining the Value of Statistical Life by means of empirical methods and based on societal preferences might circumvent the problems associated with the IVSL and needs further exploration.

Economic evaluation of duloxetine for the treatment of women with stress urinary incontinence: a Markov model comparing pharmacotherapy with pelvic floor muscle training.

BACKGROUND: Duloxetine is a serotonin and norepinephrine reuptake inhibitor and may be useful for treating women with stress urinary incontinence (SUI) in general practice. OBJECTIVE: The objective of this study was to examine the cost-effectiveness of 2 duloxetine strategies (duloxetine alone and duloxetine after inadequate response to pelvic floor muscle training [PFMT]) compared with PFMT or no treatment for women aged>or=50 years with SUI. METHODS: A Markov model with a 3-month cycle length was developed, with a time horizon of 5 years. Incontinence severity was based on incontinence episode frequency per week (IEF/week). Four SUI health states were distinguished in the model: no SUI (0 incontinence episode [IE] per week), mild SUI (19 IEs/week), moderate SUI (10-25 IEs/week), and severe SUI (>or=26 IEs/week). Transition probabilities were calculated, based on published evidence, expert opinion, and demographic data. Outcomes were expected total societal costs and expected IEs. The analysis was performed from the societal perspective of The Netherlands, and all costs were reported in year-2002 euros. One-way sensitivity and probabilistic sensitivity analyses were performed. RESULTS: In the model, providing PFMT cost euro0.03/IE avoided, compared with no treatment. Duloxetine after inadequate PFMT cost euro3.81/IE avoided, compared with PFMT One-way sensitivity analyses indicated that these results were robust regarding variation in age, IEF/week, and discount rate. Below the ceiling ratio of euro3.65/IE avoided, PFMT had the highest probability of being cost-effective. With higher ceiling ratios, duloxetine after inadequate PFMT had the highest cost-effectiveness probability. CONCLUSIONS: Treating patients with duloxetine after inadequate PFMT response yielded additional health effects in the model, but would require society in The Netherlands to pay euro3.81/IE avoided for women aged>or=50 years with SUI being treated in general practice. It is up to policy-makers to determine whether this ratio would be acceptable.

Selective prescribing of atypical antipsychotics.

PURPOSE: The aim of the study was to investigate whether the most recent introduced atypical antipsychotics olanzapine and risperidone were preferentially prescribed to patients susceptible to develop extrapyramidal side effects (EPS) and those not responding adequately to typical antipsychotics. METHODS: Data were obtained from the Dutch PHARMO system that includes complete medication and hospital admission records of 675 000 residents of 14 Dutch cities. A total number of 129 new users of olanzapine and 142 new users of risperidone as well as 507 new users of typical antipsychotic drugs were identified from our database in the period of 1996-1998. The prevalence of markers of EPS, therapy resistance and therapy non-compliance were assessed in the period of 1 year prior to a new start of an antipsychotic. RESULTS: New use of olanzapine and risperidone was significantly associated with previous use of other antipsychotics (odds ratio 4.0, 95%CI: 2.5-6.7 and odds ratio 3.0, 95%CI: 2.0-4.7, respectively). New use of olanzapine and risperidone was also associated with previous use of anticholinergic drugs compared to users of typical antipsychotics (over three and two times more, respectively). This effect diminished when adjusted for previous use of antipsychotics. CONCLUSIONS: In particular olanzapine and also risperidone were selectively prescribed to patients formerly treated with other antipsychotics and to those susceptible for EPS. If not recognised or controlled for, observational studies comparing different antipsychotic drugs may produce biased results on efficacy or frequency of side effects for the different types of antipsychotics.

Prevalence and incidence of severe sepsis in Dutch intensive care units.

INTRODUCTION: Severe sepsis is a dreaded consequence of infection and necessitates intensive care treatment. Severe sepsis has a profound impact on mortality and on hospital costs, but recent incidence data from The Netherlands are not available. The purpose of the present study was to determine the prevalence and incidence of severe sepsis occurring during the first 24 hours of admission in Dutch intensive care units (ICUs). METHODS: Forty-seven ICUs in The Netherlands participated in a point prevalence survey and included patients with infection at the time of ICU admission. Clinical symptoms of severe sepsis during the first 24 hours of each patient's ICU stay were recorded and the prevalence of severe sepsis was calculated. Then, the annual incidence of severe sepsis in The Netherlands was estimated, based on the prevalence, the estimated length of stay, and the capacity of the participating ICUs relative to the national intensive care capacity. RESULTS: The participating ICUs had 442 beds available for admissions, which was estimated to be 42% of the national ICU capacity. At the time of the survey, 455 patients were currently admitted and 151 were included in the analysis; 134 (29.5%) patients met criteria for severe sepsis. The most common failing organ system was the respiratory system (90%), and most patients were admitted following surgery (37%) and were admitted because of acute infection (62%). The most prevalent source of infection was the lung (47%). The estimated duration of ICU stay for severe sepsis patients was 13.3 +/- 1.1 days. CONCLUSION: The annual number of admissions for severe sepsis in Dutch ICUs was calculated at 8643 +/- 929 cases/year, which is 0.054% of the population, 0.61% of hospital admissions and 11% of ICU admissions.