Marco Chiumente

Ipilimumab in real-world clinical practice: efficacy and safety data from a multicenter observational study

In patients with metastatic melanoma, ipilimumab has been shown to improve long-term survival. This observational multicenter study reports clinical outcomes of 418 patients treated with second-line ipilimumab from February 2013 to August 2014. Median overall survival (OS) was 6.43 months (95%CI: 5.45–7.42; n = 300), while median progression-free survival (PFS) was 3.7 months (95%CI: 3.23–4.17; n = 188). Demographic factors, such as sex or number of previous therapies did not affect OS. Survival was shorter in patients with ECOG > 0 (Eastern Cooperative Oncology Group, Performance Status) (p < 0.001), while a longer OS was found in patients who completed all four therapy cycles (p < 0.001). Adverse events of any grade were reported for 66% of patients (mainly cutaneous and gastrointestinal), but most were low grade and easily managed. Adverse events of grades 3–4 were observed in 13% of patients. This study confirmed the efficacy and safety of this treatment in real practice.

CAPACITY BUILDING IN AGENCIES FOR EFFICIENT AND EFFECTIVE HEALTH TECHNOLOGY ASSESSMENT

OBJECTIVESnHealth technology assessment (HTA) yields information that can be ideally used to address deficiencies in health systems and to create a wider understanding of the impact of different policy considerations around technology reimbursement and use. The structure of HTA programs varies across different jurisdictions according to decision-maker needs. Moreover, conducting HTA requires specialized skills. Effective decision making should include multiple criteria (medical, economic, technical, ethical, social, legal, and cultural) and requires multi-disciplinary teams of experts working together to produce these assessments. A workshop explored the multi-disciplinary skills and competencies required to build an effective and efficient HTA team, with a focus on low- and middle-income settings.nnnMETHODSnThis proceeding summarizes main points from a workshop on capacity building, drawing on presentations and group discussions among attendees including different points of view.nnnRESULTS AND CONCLUSIONSnThe workshop and thus this study would have benefited from a larger variety of stakeholders. Therefore, the conclusions arising from the workshop are not the opinion of a representative sample of HTA professionals. Nonetheless, organizations and speakers were carefully selected to provide a valuable approach to this theme. Thus, these proceedings highlight some of the gaps and needs in the education and training programs offered worldwide and calls for further investigation.

Comorbidity, Polytherapy, and Drug Interactions in a Neurological Context: An Example of a Multidisciplinary Approach to Promote the Rational Use of Drugs

Purpose: A high number of adverse drug reactions (ADRs), mainly caused by drug–drug interactions (DDIs), occur in neurological wards and few data are available about incidence and prevalence of DDIs in this context. This study investigated—(1) the prevalence of drug–drug and drug–disease interactions in patients admitted to a neurological unit in Italy, (2) the risk factors for DDIs, and (3) the diseases and the drug classes mostly involved in drug–drug and drug–disease interactions. Methods: For 2 months, we performed a retrospective, observational study in the neurological unit of St Bassiano Hospital, enrolling 79 patients who received a drug prescription at discharge. Results: About half of the patients were discharged with 5 or more prescribed drugs, and 72% of patients showed potential, clinically relevant DDIs. Linear correlations were observed between age and number of prescribed drugs (P < .01) and between age and number of interactions (P < .01). The number of prescribed drugs was associated with the number of detected DDIs (P < .01). The application of drug interaction alerts and the use of medication inappropriateness criteria (ie, Beers criteria) were not satisfactory in choosing the best therapy for each patient. Therefore, multidisciplinary discussions of each clinical case was required. Conclusion: The study demonstrated that the neurological patient, especially if elderly, has a high risk of DDI and ADRs and that many of these can be avoided by case discussion in multidisciplinary team meetings, in which the presence of a dedicated clinical pharmacist is crucial.

Optimization of resources by drug management: A multicentred web-administered study on the use of ipilimumab in Italy

Objective In a scenario of new expensive cancer therapies entering the market, strategies of optimisation and cost containment are crucial in oncology care. Better management of drug waste and centralization of drug preparation can be effective strategies to achieve these goals. The aim of this work is to describe the economic management of a high cost anticancer drug (ipilimumab) in some Italian reference centres. Methods This was an observational, multicentred study in which economical and clinical data of 21 cancer centres (418 patients) were collected during the enrollment period from February 2013 to August 2014. The follow-up period ended in July 2015. Results Participants purchased 10.7% more vials of ipilimumab than necessary for compounding. The results were variable among centres, and only five centres had a deviation lower than 5% between the drug purchased and the drug prescribed. Hospitals applying the drug day reached a statistically significant residual of drug effectively used compared to the amount prescribed (Pu2009=u20090.018). Consequently, the price for treating a model patient was significantly lower in those hospitals (median spare of 7456 euro per patient). Conclusions This study demonstrated that the careful management of drug waste and the application of drug-day, through a proper selection of vial and the ability to use the leftover drug, can generate economic savings. However, tailoring the drug stock to clinical need is still an open issue which deserves further analysis.

Ulipristal acetate for pre-operative management of uterine fibroids: Modeling outcomes and costs

OBJECTIVESnThe aim of this study was to evaluate the pharmacoeconomic profile in Italy of preoperative treatment with ulipristal acetate at the dose of 5u202fmg/day for 13 weeks in comparison with placebo prior to surgical management of symptomatic uterine fibroids.nnnSTUDY DESIGNnThe pharmacoeconomic analysis was based on the calculation of incremental cost-effectiveness ratio (ICER). Effectiveness data were derived from the randomized-controlled trial PEARL-1, whilst costs data were retrieved from the published literature. A Markov model was employed to simulate the pattern of costs and two univariate sensitivity analyses tested the robustness of the results.nnnRESULTSnIn comparison with placebo, ulipristal acetate 5u202fmg for presurgical therapy was estimated to be associated with an incremental cost of €351 per patient. Costs per patient were €3836 for ulipristal acetate vs €3485 for placebo. The incremental effectiveness was 0.01931 QALYs per patient (around 7 quality-adjusted days per patient). Hence, the cost effectiveness ratio was calculated to be €18,177 per QALY gained.nnnCONCLUSIONSnPreoperative use of ulipristal acetate 5u202fmg in patients with uterine fibroids has a favourable pharmacoeconomic profile.

Rituximab biosimilar evaluated by network meta-analysis

The growing health care needs and the increase of new and expensive health care technologies are a challenge for the sustainability of health systems worldwide.[1][1] Globally, national health systems are currently spending around US

The Life Cycle of Health Technologies. Challenges and Ways Forward

100 billion per year on anticancer drugs alone.[2][2]

Burden of uterine fibroids in Italy: epidemiology, treatment outcomes, and consumption of health care resources in more than 5,000 women

Osteba, Basque Office for Health Technology Assessment (HTA), Ministry for Health, Basque Government, Vitoria-Gasteiz, Spain, 2 Societá Italiana di Farmacia Clinica e Terapia (SIFaCT) – Italian Society of Clinical Pharmacy and Therapeutics, Milan, Italy, German Agency for Health Technology Assessment (DAHTA), Deutsches Institut für Medizinische Dokumentation und Information (DIMDI), Cologne, Germany

Differences in Effectiveness among Devices for Endovascular Thrombectomy in Patients with Acute Ischemic Stroke

Background and purpose Epidemiological studies on uterine fibroids (UFs) are mostly based on surveys or analyses of small samples of patients. In 50% of women, the quality of life is worsened by disease-related symptoms; furthermore, treatments imply a remarkable health care cost. The aim of this observational study was to analyze a large sample of Italian patients with UFs and to assess the epidemiology, the appropriateness of treatments, and the consumption of disease-related resources. Methods Data were collected through a data-linkage technique from five administrative databases. Women aged between 18 and 55 years and resident in three local health authorities (north–central–south Italy) were selected over the period from 1st January 2009 to 31st December 2015. The inclusion criteria were a surgical procedure with diagnosis of UFs or a pharmacological treatment with gonadotropin-releasing hormone (GnRH) analogs or ulipristal acetate. Besides the overall descriptive analysis, two comparisons were evaluated: surgery versus no surgery and treatment with GnRH analogs versus ulipristal acetate. Results A total of 5,665 women with UFs were selected from an overall population of 2,400,000 people. In the north, 73.6% of patients underwent surgery, as opposed to only 16.7% in the south; 70% of surgeries were hysterectomies. The average cost per patient was €3,249 (duration of follow-up = up to 7 years). The southern district had the highest number of drug prescriptions; in particular, 49% of patients took >10 packages of GnRH analogs. Conclusion This study is the first on this topic conducted in Italy using a large sample size. The analysis of resource consumption revealed a high heterogeneity in the choice of drug treatments by gynecologists (especially in the south); in the north, marked variations were seen in the rates of surgery. The long-term use of GnRH was inappropriate.

Burden of Stroke in Italy: An Economic Model Highlights Savings Arising from Reduced Disability following Thrombolysis

Dear Sir: n nIn the treatment of acute ischemic stroke, the proofs of effectiveness for endovascular thrombectomy have become more robust in recent times, but some questions remain on whether the effectiveness differs across different devices (e.g. Trevo, Merci, and Solitaire). In the absence of studies that have directly compared these devices with one another, comparative information relies on the results of meta-analyses, and particularly on indirect meta-analytic comparisons conducted with a network design. n nIn 2013, we published the first network meta-analysis in this field [1] in which we evaluated three devices (Merci, Trevo, and Solitaire) based on pivotal randomized trials. Both Trevo and Solitaire were found to be more effective than Merci, but the information was not sufficient to determine if Solitaire was more effective also than Trevo. n nBetween 2013 and 2015, numerous randomized controlled trials (RCTs) evaluating these devices have been made available. Three “traditional” pairwise meta-analyses, that synthesized the effectiveness data resulting from direct comparisons, have been published in the Journal of Stroke [2], JAMA [3], and Journal of American College of Cardiologists [4], but no network meta-analysis based on the more mature evidence currently available has been conducted. n nThe meta-analysis by Hong et al. [2] (15 trials) found that endovascular recanalization therapy was associated with increased good outcomes (0-2 modified Ranking Scale) compared to the controls given standard therapy (including intravenous tissue plasminogen activator in 9 trials); the odds ratio (OR) was 1.79 (95% confidence interval, 1.34 to 2.40). Likewise, the meta-analysis by Badhiwala et al. [3] (8 RCTs) found that, as compared with thrombolysis, the endovascular interventions increased the rate of functional independence at 90 days (0-2 modified Ranking Scale) with an OR of 1.71 (95% confidence interval: 1.18 to 2.49). Also the meta-analysis by Elgendy et al. [4] investigated the trials comparing thrombectomy with standard thrombolysis (8 RCTs), and its results were virtually identical to those reported by Badhiwala et al. [3]. n nHowever, no indirect comparisons between individual devices were made in these three meta-analyses even though, for practical reasons, this information can be of great interest. n nIn this report, we describe one such network meta-analysis with indirect comparisons focused on these devices. Our description of these results was limited to a re-analysis of the standard pairwise meta-analysis data published by Badhiwala et al. [3] (see Table 1 of Reference 3; total number of patients=2,387), which we re-evaluated by application of a Bayesian network meta-analysis [5]. As in Badhiwala’s study, our clinical material consisted of 8 RCTs comparing a stent-based endovascular intervention (treatment group) with thrombolysis (controls). Four of these trials did not employ, in the treatment group, a single device but three or more of these (typically: Penumbra or Trevo or Merci or Solitaire) while the remaining four trials employed Solitaire. The ESCAPE trial, in which Solitaire was employed in 66% of the patients of the treatment group, was classified among the four studies employing Solitaire. Functional independence at 90 days was our end-point. The OR, accompanied by its 2.5% to 97.5% credible interval (CrI), was the outcome measure of our analysis. Since we anticipated some heterogeneity in the clinical material, our primary analysis used the random-effect model, but also the fixed-effect one was tested [5]. n nThe results of our Bayesian meta-analysis (random-effect model) showed that the patient group receiving any device had a numerical, but not significant higher incidence of functional independence than the controls (OR=1.20; CrI: 0.71 to 1.91). In contrast, the group receiving Solitaire had a significantly better incidence of this end-point as compared with the controls (OR= 2.52; CrI: 1.51 to 4.33). In the indirect comparison between Solitaire and any stent, the former had a significantly better effectiveness (OR=2.11; CrI: 1.06 to 4.48). n nFigure 1 shows the ranking in effectiveness, an information that is typical of all Bayesian analyses; Solitaire ranked first (median rank=1; CrI: 1 to 1) followed by any stent (median rank=2; CrI: 2 to 3) and by thrombolysis (median rank=3; CrI: 2 to 3). The results in terms of OR calculated according to the fixed effect model were quite similar (data not shown in detail) even though, as expected, the CrIs were somewhat narrower. According to this model, the indirect comparison between Solitaire and any stent showed an OR of 2.07 (CrI: 1.43 to 2.97). n n n nFigure 1. n nComparative effectiveness of two endovascular interventions and thrombolysis evaluated according to Bayesian network meta-analysis (8 randomized studies; end-point=functional independence at 90 days). The figure shows the histogram of rankings estimated ... n n n nThere was a significant degree of heterogeneity in the clinical material (8 RCTs) included in the meta-analysis by Badhiwala et al. [3]; this is generally considered a negative factor that limits the value of the evidence concerned [6]. To study in more depth the degree of heterogeneity of this clinical material, in a separate analysis [6] we selected the four RCTs that directly compared Solitaire with thrombolysis and we carried out a traditional pairwise meta-analysis. Interestingly enough, the pooled results from these 4 trials (end point: functional independence at 90 days) showed no heterogeneity with a significantly better effectiveness for the Solitaire group (pooled odds-ratio=2.47; 95% confidence interval: 1.84 to 3.33; I2=0%, P value for heterogeneity=0.689) [6]. n nIn summary, the main advantages of our re-analyses of this clinical material include the evaluation of the most updated evidence on this topic and the use of a statistical technique that allows an indirect comparison between the devices. Our indirect comparisons indicate that Solitaire has a significantly better effectiveness than that of the other devices. However, owing to the well-known limitations of network meta-analyses [5] and to the presence of heterogeneity in the overall series of 8 RCTs, our findings represent a hypothesis that needs further confirmation from other trials.