The role of fentanyl in the treatment of breakthrough cancer pain: Different biotechnologies, different results and different drug costs.

The aim of this paper was to assess the drug costs of the different biotechnologies (intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT)) in the treatment of breakthrough cancer pain (BTCP). We have calculated the mean drug costs (expressed in euros (€)) for patients treated for BTCP. INFS resulted the less expensive towards OTFC and FBT, with 697 440 €versus (vs.) 809 552 €vs. 779 662 €every 100 patients treated for BTCP, respectively. In conclusion, combining drug costs of different biotechnologies (INFS, OTFC and FBT) with the measure of efficacy represented by the reduction of BTCP avoided (incremental cost-effectiveness ratio, ICER), INFS resulted in better cost-effectiveness.

Clinical and Economic Analysis of Morphine Versus Fentanyl in Managing Ventilated Neonates With Respiratory Distress Syndrome in the Intensive Care Setting.

PURPOSE: Morphine and fentanyl opioids are common analgesic agents for consideration in the neonatal intensive care unit (NICU) for neonates with respiratory distress syndrome (RDS) and undergoing mechanical ventilation (MV). The aim of this study was to evaluate the clinical and economic impact of morphine versus fentanyl in neonates with RDS undergoing MV. METHODS: Retrospective cost-effectiveness analysis of critically ill neonates with RDS receiving standard doses of morphine versus fentanyl at Women's Wellness and Research Center, Qatar. Clinical data of neonates were extracted from medical records of patients from 2014 to 2016. A decision analytic model based on the hospital's perspective was constructed to follow possible consequences of the initial dosing of analgesia, before potential titration. Primary end points were successful pain relief rate based on the Premature Infant Pain Profile scale and overall direct medical cost of therapy. Study population of 126 neonates was used to achieve results with 80% power and 0.05 significance. Sensitivity analysis was conducted to enhance robustness of conclusions against input uncertainties and to increase generalizability of results. FINDINGS: Morphine achieved a success of 68% versus 43% with fentanyl (risk ratio = 1.72; 95% CI, 1.16-2.56; P = 0.0075). Morphine was associated with a minimal incremental cost-effectiveness ratio of USD 135 per additional case of successful pain relief over fentanyl. Higher morphine cost was reported in 2% of cases. Sensitivity analysis found model insensitivity to input uncertainties except NICU stay and cost of MV. IMPLICATIONS: This is the first cost-effectiveness evaluation of morphine versus fentanyl in the NICU. Morphine significantly improved the relieve of pain over fentanyl. It had 98% probability of dominance over fentanyl. Results in this study support the use of morphine over fentanyl as first-line monotherapy with MV in NICU settings.

Illicit fentanyls in the opioid street market: desired or imposed?

BACKGROUND: Illicitly manufactured fentanyl and its analogues are appearing in countries throughout the world, often disguised as heroin or counterfeit prescription pills, with resulting high overdose mortality. Possible explanations for this phenomenon include reduced costs and risks to heroin suppliers, heroin shortages, user preferences for a strong, fast-acting opioid and the emergence of Dark Web cryptomarkets. This paper addresses these potential causes and asks three questions: (1) can users identify fentanyl; (2) do users desire fentanyl; and (3) if users want fentanyl, can they express this demand in a way that influences the supply? ARGUMENT/ANALYSIS: Existing evidence, while limited, suggests that some users can identify fentanyl, although not reliably, and some desire it, but because fentanyl is frequently marketed deceptively as other drugs, users lack information and choice to express demand effectively. Even when aware of fentanyl's presence, drug users may lack fentanyl-free alternatives. Cryptomarkets, while difficult to quantify, appear to offer buyers greater information and competition than offline markets. However, access barriers and patterns of fentanyl-related health consequences make cryptomarkets unlikely sources of user influence on the fentanyl supply. Market condition data indicate heroin supply shocks and shortages prior to the introduction of fentanyl in the United States and parts of Europe, but the much lower production cost of fentanyl compared with heroin may be a more significant factor CONCLUSION: Current evidence points to a supply-led addition of fentanyl to the drug market in response to heroin supply shocks and shortages, changing prescription opioid availability and/or reduced costs and risks to suppliers. Current drug users in affected regions of the United States, Canada and Europe appear largely to lack both concrete knowledge of fentanyl's presence in the drugs they buy and access to fentanyl-free alternatives.

Economic assessment of postoperative pain control strategies for treatment of adult patients with cancer / Avaliação econômica de estratégias para controle da dor pós-operatória para tratamento de pacientes adultos com câncer

Summary Objective: The authors performed an economic assessment of opioids currently being used for control of postoperative pain relating to the surgical treatment of cancer (fentanyl and sufentanil) within the Brazilian Unified Health System (SUS, in the Portuguese acronym). Method: The assessment was based on the perspective of the government, in order to collaborate with the promotion of effectiveness in public policies of health, and to optimize the allocation of public resources into health. A cost-effectiveness analysis was performed using data collected from the Brazilian Unified Health System and information from literature review, in order to build a decision tree on the alternatives for control of postoperative pain related to cancer treatment among adult patients. The outcomes considered were: effectiveness of postoperative analgesia and occurrence of nausea and vomit in the 48 hour period after surgery, and additional 24-hour cycles in patient follow-up. A univariate sensitivity analysis was conducted in order to verify robustness of the model estimated. Results: Literature review showed a limited number of studies directly comparing fentanyl and sufentanil for control of postoperative pain. The adoption of sufentanil (cost = U$ 25.72 / outcome = 1.6 VAS points) was dominant in relation to the use of fentanyl (cost = U$ 32.58 / outcome = 2.6 VAS points). The estimated model showed robustness in relation to changes in the parameters analyzed. Conclusion: Sufentanil presented higher cost-effectiveness ratio in relation to fentanyl for control of postoperative pain in surgeries related to cancer treatment among adult patients in the Brazilian Unified Health System.

Resumo Objetivo: O artigo apresenta uma avaliação econômica de opioides atualmente utilizados no controle de dor pós-operatória relacionada ao tratamento cirúrgico do câncer (fentanil e sufentanil) no contexto do Sistema Único de Saúde. Método: A avaliação baseou-se na perspectiva do governo, de forma a colaborar na promoção da efetividade das políticas públicas de saúde e melhorar a alocação de recursos públicos em saúde. Uma análise custo-efetividade foi realizada a partir de dados coletados no Sistema Único de Saúde e de informações provenientes de revisão da literatura para construção de uma árvore de decisão contendo alternativas para controle de dor pós-operatória relacionada ao tratamento cirúrgico do câncer entre pacientes adultos. Os desfechos considerados foram: efetividade da analgesia pós-operatória e ocorrência de náusea e vômito no período de 48 horas após cirurgia e em ciclos adicionais de 24 horas de seguimento do paciente. Uma análise de sensibilidade univariada foi conduzida para verificar a robustez do modelo estimado. Resultados: Na revisão de literatura, um número limitado de estudos efetuou comparação direta entre fentanil e sufentanil no controle de dor pós-operatória. A adoção de sufentanil (custo = U$ 25,72 / desfecho = 1,6 pontos VAS) foi dominante em relação ao uso do fentanil (custo = U$ 32,58 / desfecho = 2,6 pontos VAS). O modelo estimado demonstrou robustez em relação a mudanças nos parâmetros analisados. Conclusão: O sufentanil apresentou razão custo-efetividade superior em relação ao fentanil no controle de dor pós-operatória em cirurgias relacionadas ao tratamento de câncer entre pacientes adultos no Sistema Único de Saúde.

Silicon to syringe: Cryptomarkets and disruptive innovation in opioid supply chains.

Cryptomarkets offer insight into the evolving interplay between online black markets and cartel-based distribution. The types and forms of heroin, fentanyl, and prescription drugs show wide diversification. In this commentary we describe changes in the conceptualizations, technologies and structures of drug supply chains in the 21st Century, with special attention to the role of cryptomarkets as tools, contexts, and drivers of innovation in public health research.

Cost-effectiveness analysis of oral fentanyl formulations for breakthrough cancer pain treatment.

Breakthrough cancer Pain (BTcP) has a high prevalence in cancer population. Patients with BTcP reported relevant health care costs and poor quality of life. The study assessed the cost-effectiveness of the available Oral Fentanyl Formulations (OFFs) for BTcP in Italy. A decision-analytical model was developed to estimate costs and benefits associated with treatments, from the Italian NHS perspective. Expected reductions in pain intensity per BTcP episodes were translated into, percentage of BTcP reduction, resource use and Quality-Adjusted-Life-Years (QALYs). Relative efficacy, resources used and unit costs data were derived from the literature and validated by clinical experts. Probabilistic and deterministic sensitivity analyses were performed. At base-case analysis, Sublingual Fentanyl Citrate (FCSL) compared to other oral formulations reported a lower patient's cost (€1,960.8) and a higher efficacy (18.7% of BTcP avoided and 0.0507 QALYs gained). The sensitivity analyses confirmed the main results in all tested scenarios, with the highest impact reported by BTcP duration and health care resources consumption parameters. Between OFFs, FCSL is the cost-effective option due to faster reduction of pain intensity. However, new research is needed to better understand the economic and epidemiologic impact of BTcP, and to collect more robust data on economic and quality of life impact of the different fentanyl formulations. Different fentanyl formulations are available to manage BTcP in cancer population. The study is the first that assesses the different impact in terms of cost and effectiveness of OFFs, providing new information to better allocate the resources available to treat BTcP and highlighting the need of better data.

Economic assessment of postoperative pain control strategies for treatment of adult patients with cancer.

OBJECTIVE: The authors performed an economic assessment of opioids currently being used for control of postoperative pain relating to the surgical treatment of cancer (fentanyl and sufentanil) within the Brazilian Unified Health System (SUS, in the Portuguese acronym). METHOD: The assessment was based on the perspective of the government, in order to collaborate with the promotion of effectiveness in public policies of health, and to optimize the allocation of public resources into health. A cost-effectiveness analysis was performed using data collected from the Brazilian Unified Health System and information from literature review, in order to build a decision tree on the alternatives for control of postoperative pain related to cancer treatment among adult patients. The outcomes considered were: effectiveness of postoperative analgesia and occurrence of nausea and vomit in the 48 hour period after surgery, and additional 24-hour cycles in patient follow-up. A univariate sensitivity analysis was conducted in order to verify robustness of the model estimated. RESULTS: Literature review showed a limited number of studies directly comparing fentanyl and sufentanil for control of postoperative pain. The adoption of sufentanil (cost = U$ 25.72 / outcome = 1.6 VAS points) was dominant in relation to the use of fentanyl (cost = U$ 32.58 / outcome = 2.6 VAS points). The estimated model showed robustness in relation to changes in the parameters analyzed. CONCLUSION: Sufentanil presented higher cost-effectiveness ratio in relation to fentanyl for control of postoperative pain in surgeries related to cancer treatment among adult patients in the Brazilian Unified Health System.

Opioid therapy in the treatment of chronic pain conditions in Germany.

BACKGROUND: Primarily used for treating malignant pain, opioids are recently applied for chronic non-tumor pain. For the lack of evidence based strategies from long-term studies, opioids are discussed controversially, esp. considering cost-benefit. OBJECTIVES: The purpose of this study is to evaluate characteristics in prescribing opioids for tumor and non-tumor pain conditions. STUDY DESIGN: Cost effectiveness study/observational study SETTING/METHODS: Health insurance data of a German statutory health insurance company (N = 6.800.000, data acquisition from 2006 to 2010) was evaluated by assigning opioid prescriptions to certain pain related diagnoses using CART (Classification And Regression Tree) segmentation analysis. Age- and gender-specific characteristics of prescriptions were calculated. RESULTS: The number of prescriptions of opioid prescriptions increased linearly. Prescriptions of mild opioids were decreasing for non-tumor pain, but increasing for tumor pain, while the number of prescriptions of strong opioids was increasing both for tumor and nontumor pain. Differences occurred in terms of duration and kind of the preferred substances, including the considerations of common contraindications (e.g. somatoform disorders). The majority of strong opioids being prescribed for non-tumor pain were fentanyl pain patches for 40 to 45 year old males with average annual costs of 1833 Euros per patient. Out of 21000 patients with somatoform pain disorder, 44.4% were treated with opioids (20.7% with mild, 23.7% with strong opioids). LIMITATIONS: The results did not consider if the opioid medication was actually taken by the patients. Another difference in terms of representativeness might occur since the gender distribution varies between the official statistical data and data collected by the health insurance company. Because of the acquisition of the data, no conclusions about possible correlation of pain syndromes and educational and social classes are possible. Tumor patients who received an opioid prescription for non-tumor pain could not be excluded. CONCLUSIONS: While the overall expenditure of the health insurance companies increased, it remains unknown which patient is receiving a particular opioid medication. Prescribing behavior was often not consistent with common indications and contraindications.

[Use of fendivia transdermal therapeutic system in Russian patients with malignant neoplasms during palliative care: pharmacoeconomic aspects].

AIM: To make a comparative clinical and economic assessment of a transdermal therapeutic system (TTS) for fendivia and traditional opioid analgesics in patients with malignant neoplasms (MN) during palliative care. MATERIALS AND METHODS: Pharmacoeconomic analysis of opioid analgesics used in patients with MN during analgesic therapy was made using the cost-effectiveness analysis in the framework of a budget impact analysis (BIA). RESULTS: The assessment of the medical cost structure in the fendivia and morphine groups (100 patients in each group), which was made in the framework of BIA, demonstrated that the cost of pharmacotherapy in the fendivia group was comparable with that of an ambulance call for additional analgesia and correction of the side effects of performed therapy (615,804.00 and 645,337.60 rbl. monthly, respectively). At the same time, in the morphine group the cost of an ambulance call was more than 20 times that of pharmacotherapy (2,117,514.00 and 93,120.00 rbl. monthly, respectively). Thus, the total savings from applying the fendivia TTS in the group of 100 patients ranged up to 949,492.40 rbl. monthly. CONCLUSION: The application of the fendivia TTS is clinically and pharmacoeconomically valid and leads to a considerable reduction in public health care costs.

Cost-effectiveness analysis of transnasal fentanyl citrate for the treatment of breakthrough cancer pain.

INTRODUCTION: Pain is a symptom of cancer and is categorized in two forms: background pain to be treated with analgesics, and breakthrough cancer pain (BTcP), which needs drug treatment on demand. We present a cost-effectiveness analysis of transnasal fentanyl citrate as an alternative to morphine. METHODS: A Markov model considers a cohort of 100 patients on a daily basis. Effectiveness was included by selecting three clinical studies. Side effects, hospitalizations and visits were valued by referring to national formularies. Utility data were used to differentiate the health status inherent to BTcP. RESULTS: The incremental cost-effectiveness ratio of transnasal fentanyl citrate is 10,140 euros/QALY. Sensitivity analysis shows that with a threshold of 30,000 euros/QALY, the treatment of BTcP with transnasal fentanyl citrate would have an 86% probability of being cost-effective. CONCLUSION: Transnasal Fentanyl citrate is cost-effective, therefore represents a good investment in health.

The pharmacoeconomics of breakthrough cancer pain.

Breakthrough cancer pain (BTP) has a significant impact on patients' activities of daily living, family, and the society; however, the economic ramifications of BTP are largely unknown. This review aims to summarize the available pharmacoeconomics studies of BTP in the context of the availability of several formulations of rapid-onset opioids administered by various routes, which are significantly more expensive than oral opioids. A systematic literature search of PubMed and Tufts registry through August 2012 was conducted using key words including "breakthrough cancer pain" and "cost effectiveness." After exclusion of irrelevant articles, a total of six articles were included. Studies reviewed include two economic survey studies, two quality improvement projects, and two decision-analytic models. These studies demonstrate BTP causes significant financial burden to patients and society through increased hospitalization and health care utilization. Only one study comparing placebo with intranasal fentanyl spray, oral transmucosal fentanyl citrate, and oral transmucosal fentanyl buccal tablet has demonstrated the cost-effectiveness of these rapid-onset opioids for the treatment of BTP. Overall, there is a lack of pharmacoeconomic studies for BTP management with rapid-onset opioids. Further study is warranted assessing the net benefit of rapid-onset opioids to oral opioids to assist decision-making by patients, clinicians, and payers.

Comparison between the recovery time of alfentanil and fentanyl in balanced propofol sedation for gastrointestinal and colonoscopy: a prospective, randomized study.

BACKGROUND: There is increasing interest in balanced propofol sedation (BPS) titrated to moderate sedation (conscious sedation) for endoscopic procedures. However, few controlled studies on BPS targeted to deep sedation for diagnostic endoscopy were found. Alfentanil, a rapid and short-acting synthetic analog of fentanyl, appears to offer clinically significant advantages over fentanyl during outpatient anesthesia.It is reasonable to hypothesize that low dose of alfentanil used in BPS might also result in more rapid recovery as compared with fentanyl. METHODS: A prospective, randomized and double-blinded clinical trial of alfentanil, midazolam and propofol versus fentanyl, midazolam and propofol in 272 outpatients undergoing diagnostic esophagogastroduodenal endoscopy (EGD) and colonoscopy for health examination were enrolled. Randomization was achieved by using the computer-generated random sequence. Each combination regimen was titrated to deep sedation. The recovery time, patient satisfaction, safety and the efficacy and cost benefit between groups were compared. RESULTS: 260 participants were analyzed, 129 in alfentanil group and 131 in fentanyl group. There is no significant difference in sex, age, body weight, BMI and ASA distribution between two groups. Also, there is no significant difference in recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between two groups. Though deep sedation was targeted, all cardiopulmonary complications were minor and transient (10.8%, 28/260). No serious adverse events including the use of flumazenil, assisted ventilation, permanent injury or death, and temporary or permanent interruption of procedure were found in both groups. However, fentanyl is New Taiwan Dollar (NT$) 103 (approximate US$ 4) cheaper than alfentanil, leading to a significant difference in total cost between two groups. CONCLUSIONS: This randomized, double-blinded clinical trial showed that there is no significant difference in the recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between the two most common sedation regimens for EGD and colonoscopy in our hospital. However, fentanyl is NT$103 (US$ 4) cheaper than alfentanil in each case. TRIAL REGISTRATION: Institutional Review Board of Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry (ChiCTR-TRC-12002575).

[Economic and clinical impact of a controlled sedation procedure in an intensive care unit]. / Impact clinique et économique d'une politique de contrôle de la sédation par protocole dans un service de réanimation médicochirurgicale.

OBJECTIVE: Since the last consensus conducted by Sfar/SRLF, the use of protocol for sedation became the reference in our ICUs. Decrease in length of stay and length of mechanical ventilation with used of these protocols have been already described. We would like to investigate the economic impact associated. STUDY DESIGN: Using the PMSI data, we studied retrospectively, the economic effect, one year before and one year after protocol implementation in our ICU. METHOD: The economic evaluation compared the cost of sedation but also the cost of mechanical ventilation and length of stay in ICU. RESULTS: Characteristic and number of patients were equivalent during the two years. We described a significant decrease in length of mechanical ventilation (8.8 vs. 8.4; p<0.05) but not in length of stay (11.4 vs. 11.7; NS) between the two periods. We described a decrease of sedation cost of 11 412 euros and a decrease of mechanical ventilation cost of 27 360 Euros between the two years. CONCLUSION: We confirm in this study that use of sedation protocol in ICU is associated with a clinical impact but also with an economic effect.

An economic evaluation of short-acting opioids for treatment of breakthrough pain in patients with cancer.

OBJECTIVE: Breakthrough cancer pain (BTCP) represents a considerable economic burden. A decision-analysis model was developed to evaluate the cost-effectiveness of intranasal fentanyl spray (INFS) compared with oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT) for the treatment of BTCP. METHODS: The model was parameterized for Sweden to estimate the costs and benefits associated with treatments. Expected reductions in pain intensity (PI; measured on a numeric rating scale ranging from 0 to 10) per BTCP episodes were translated into resource use and quality-adjusted life years (QALYs). Relative analgesic efficacy of interventions was derived from a mixed treatment comparison of six randomized controlled trials. The relationship between PI and utility was obtained from a time-trade off study in the general population. Resource use and unit cost data were obtained from the literature and validated by Swedish clinical experts. The base case scenario assumed three BTCP episodes/day, a background PI of 2, and a time horizon of 180 days. Prices of INFS and OTFC were assumed to be equal with FBT ∼14% less. Uncertainty in the source data was incorporated by probabilistic sensitivity analyses and different scenario analyses. RESULTS: With INFS, 55% of BTCP (95% uncertainty interval [UI]: 46-68%) was avoided, which is greater than expected with OTFC (29%; UI 22-38%) or FBT (31%; UI 25-39%). INFS was dominating OTFC (resulting in 0.046 QALY gain and saving 174 Euros with a time horizon of 180 days) and cost-effective versus FBT (incremental cost-effectiveness ratio 12203 Euros/QALY). Despite uncertainty in the source data, there is a >99% probability that INFS is the most cost-effective intervention. CONCLUSION: Given inherent limitations of modelling studies, the greater efficacy of INFS translates to cost and QALY advantages over competing interventions in the treatment for BTCP in Sweden.

Current trends in opioid consumption globally and in Middle Eastern countries.

The overall consumption of opioids globally and in Middle Eastern countries has been in the rise during the past 3 decades. However, whereas the consumption of opiates (morphine) increased by 19.8% that of the synthetic opioids (fentanyl) increased by 31.1% for the same time period. This trend increased even further during the period 2004-2008: morphine 16.6% vs. fentanyl 45.2%. One possible explanation to this phenomenon, especially in developing countries is the notion that many patients and their families still believe that morphine hastens death. The impressive rise in the consumption of fentanyl might be associated with the fact that this drug in contrast to morphine, might not be as directly related to "opioids" as morphine.