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.

Validation of the Dutch Version of the Breakthrough Pain Assessment Tool in Patients With Cancer.

CONTEXT: Essential for adequate management of breakthrough cancer pain is a combination of accurate (re-)assessment and a personalized treatment plan. The Breakthrough Pain Assessment Tool (BAT) has been proven to be a brief, multidimensional, reliable, and valid questionnaire for the assessment of breakthrough cancer pain. OBJECTIVES: The aim of this study was to examine the validity and reliability of the Dutch Language version of the BAT (BAT-DL) in patients with cancer. METHODS: The BAT was forward-backward translated into the Dutch language. Thereafter, the psychometric properties of the BAT-DL were tested, that is factor structure, reliability (internal consistency and test-retest reliability), validity (content validity and construct validity), and the responsiveness to change. RESULTS: The BAT-DL confirmed the two-factor structure in 170 patients with cancer: pain severity/impact factor and pain duration/medication efficacy factor. The Cronbach's alpha coefficient was 0.72, and the intraclass correlation for the test-retest reliability was 0.81. The BAT-DL showed to be able to differentiate between different group of patients and correlated significantly with the Brief Pain Inventory. In addition, the BAT-DL was capable to detect clinically important changes over time. CONCLUSION: The BAT-DL is a valid and reliable questionnaire to assess breakthrough pain in Dutch patients with cancer and is a relevant questionnaire for daily practice.

Assessment of the FDA Risk Evaluation and Mitigation Strategy for Transmucosal Immediate-Release Fentanyl Products.

IMPORTANCE: Transmucosal immediate-release fentanyls (TIRFs), indicated solely for breakthrough cancer pain in opioid-tolerant patients, are subject to a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) to prevent them from being prescribed inappropriately. OBJECTIVES: To evaluate knowledge assessments of pharmacists, prescribers, and patients regarding appropriate TIRF use; to describe sponsor assessments, based on claims data, of whether the REMS program was meeting its goals; and to characterize how the FDA responded to REMS assessments. DESIGN, SETTING, AND PARTICIPANTS: Qualitative analysis of 4877 pages of FDA documents obtained through a Freedom of Information Act request, including 6 annual REMS assessment reports (2012-2017), FDA evaluations of these reports, and FDA-sponsor correspondence about safety issues. EXPOSURE: A REMS program to reduce the risk of adverse outcomes, including misuse, abuse, addiction, and overdose, arising from use of TIRFs. MAIN OUTCOMES AND MEASURES: (1) Knowledge assessments of pharmacists, prescribers, and patients; (2) survey and claims-based prescribing assessments; (3) FDA and TIRF sponsor communications; (4) modifications to the REMS program; and (5) disenrollment of noncompliant prescribers. RESULTS: Twelve months after initiation of the program, 24 of 302 pharmacists (7.9%), 35 of 302 prescribers (11.6%), and 5 of 192 patients (2.6%) incorrectly reported that TIRFs can be prescribed to opioid-nontolerant patients, with similar levels of misunderstanding maintained in the subsequent reports. At 60 months, product-specific analyses of claims data indicated that between 34.6% and 55.4% of patients prescribed TIRFs were opioid-nontolerant. In the 48-month survey, 106 of 310 prescribers (34.2%) reported prescribing TIRFs for opioid-tolerant patients with chronic, noncancer pain; at 60 months, 54 of 302 prescribers (18.4%) and 148 of 310 patients (47.7%) erroneously reported that TIRFs were FDA-approved for such use. Over the 60-month period examined, there were few substantive changes made to the REMS to address evidence of high rates of off-label TIRF use, and, although the REMS program had a noncompliance plan, there was no report of prescribers being disenrolled for inappropriate prescribing. CONCLUSIONS AND RELEVANCE: In this review of FDA documents pertaining to the TIRF REMS, surveys of pharmacists, prescribers, and patients reflected generally high levels of knowledge regarding proper TIRF prescribing, yet some survey items as well as claims-based analyses indicated substantial rates of inappropriate TIRF use. Despite these findings, the FDA did not require substantive changes to the program.

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.

Alberta Breakthrough Pain Assessment Tool: A validation multicentre study in cancer patients with breakthrough pain.

BACKGROUND: Cancer-related breakthrough pain (BTP) is a common and quite challenging pain syndrome, with significant impact on quality of life. To date, no widely recognized and validated tool for the diagnosis and evaluation of BTP exists. The Alberta Breakthrough Pain Assessment Tool (ABPAT) underwent a validation process during its development, but no experience of its implementation in clinical practice has been reported. METHODS: ABPAT was tested in a cohort of cancer patients suffering from chronic severe cancer-related pain in order to assess its acceptability and efficacy as a tool for the characterization of BTP. RESULTS: A total of consecutive 249 patients from seven different centres were included in a 2-month study period and all completed the questionnaire; 231 out of the 249 (92.8%) stated that questions were easily understandable and 217 out of the 249 (87.1%) stated that the tool allowed to explain extensively the BTP problem. Physician-patient correlation tests about baseline BTP intensity and BTP relief by medication showed statistical significance at the level of p = 0.001 and p = 0.0001, respectively. Evaluation of the efficacy of BPT medication revealed a 78.2% of patients declaring a good relief from BTP, with a significant reduction of mean BTP numeric rating scale score (p = 0.0001), but only 55.9% of patients responded to be satisfied about time for onset of the relief. CONCLUSIONS: In this study, ABPAT resulted to be a well-accepted tool for BTP assessment and characterization in a relatively large cohort of cancer patients. It is effective in discovering the unmet needs of cancer patients and in exploring the outcomes of BTP treatment.

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.

[Rapid release fentanyl administration forms. Comments of the Working Group on Tumor Pain of the German Pain Society]. / Schnell freisetzende Fentanylapplikationsformen. Stellungnahme des Arbeitskreises Tumorschmerz der Deutschen Schmerzgesellschaft.

The spectrum of indications for rapid release fentanyl preparations is controversial. For this reason the Working Group on Tumor Pain will formulate comments on how to deal with these substances. Breakthrough pain should receive individualized therapy; therefore, the use of opioids of various galenic formulations seems to be advisable. New rapid release fentanyl preparations are suitable for alleviating spontaneous breakthrough pain in tumor patients due to a rapid but short-acting effect. However, a prior optimization of the analgesic basis medication is absolutely necessary. Uncontrolled prescription for non-cancer pain must be criticized due to the problem of addiction. The medical profession should be informed about the benefits of rapid release fentanyl preparations but must also be made aware of the risk of a rapid development of addiction and tolerance. A self-commitment of the pharmaceutical industry to waive advertising for the dangerous off-label use would be desirable. In the opinion of the Working Group on Tumor Pain the use of fentanyl should be openly discussed and further scientific investigations are imperative with the aim of formulating clear recommendations.