Spending on Targeted Therapies for Duchenne Muscular Dystrophy.

This study estimates public and private spending on genetically targeted treatments for Duchenne muscular dystrophy during years in which the drugs were marketed without completed confirmatory studies.

Neighborhood disadvantage, insurance status, and molecular profiling of patients with acute myeloid leukemia.

Next-generation sequencing (NGS) is important for prognostication and determining eligibility for targeted therapies in acute myeloid leukemia (AML). The use of NGS has increased in clinical practice, but variability in testing patterns still exist. The purpose of this study was to assess trends in molecular genetic sequencing in AML based on insurance status and area deprivation index (ADI), a validated metric of neighborhood disadvantage. Patient demographics, clinical characteristics, cytogenetic and molecular data, and treatment patterns were collected retrospectively for 275 patients diagnosed with AML at a single institution. No significant differences in practice patterns and patient outcomes based on ADI rank were observed. In contrast, patients with Medicare or underinsured status were less likely to have genetic sequencing performed, were treated with less intensive regimens, and had inferior overall survival compared to those with Medicaid or private insurance. On univariate analysis, molecular genetic sequencing was associated with improved overall survival, suggesting that NGS data allows for better risk stratification and more informed therapeutic decision-making. These data highlight the current barriers to molecular genetic sequencing, demonstrate the positive benefits of NGS on clinical outcomes, and support universal coverage of NGS for all patients with AML.

Cost-effectiveness analysis of first-line treatment with crizotinib in ROS1-rearranged advanced non-small cell lung cancer (NSCLC) in Canada.

INTRODUCTION: While no direct comparative data exist for crizotinib in ROS1+ non-small cell lung cancer (NSCLC), studies have suggested clinical benefit with this targeted agent. The objective of this study was to assess the cost-effectiveness of crizotinib compared to standard platinum-doublet chemotherapy for first-line treatment of ROS1+ advanced NSCLC. METHODS: A Markov model was developed with a 10-year time horizon from the perspective of the Canadian publicly-funded health care system. Health states included progression-free survival (PFS), up to two further lines of therapy post-progression, palliation and death. Given a lack of comparative data and small study samples, crizotinib or chemotherapy studies with advanced ROS1+ NSCLC patients were identified and time-to-event data from digitized Kaplan-Meier curves were collected to pool PFS data. Costs of drugs, treatment administration, monitoring, adverse events and palliative care were included in 2018 Canadian dollars, with 1.5% discounting. An incremental cost-effectiveness ratio (ICER) was estimated probabilistically using 5000 simulations. RESULTS: In the base-case probabilistic analysis, crizotinib produced additional 0.885 life-years and 0.772 quality-adjusted life-years (QALYs) at an incremental cost of $238,077, producing an ICER of $273,286/QALY gained. No simulations were found to be cost-effective at a willingness-to-pay threshold of $100,000/QALY gained. A scenario analysis assuming efficacy equivalent to the ALK+ NSCLC population showed a slightly more favorable cost-effectiveness profile for crizotinib. CONCLUSIONS: Available data appear to support superior activity of crizotinib compared to chemotherapy in ROS1+ advanced NSCLC. At the list price, crizotinib was not cost-effective at commonly accepted willingness-to-pay thresholds across a wide range of sensitivity analyses.

How are we evaluating the cost-effectiveness of companion biomarkers for targeted cancer therapies? A systematic review.

BACKGROUND: Despite the increasing economic assessment of biomarker-guided therapies, no clear agreement exists whether existing methods are sufficient or whether different methods might produce different cost-effectiveness results. This study aims to examine current practices of modeling companion biomarkers when assessing the cost-effectiveness of targeted cancer therapies. It investigates the current methods in modeling the characteristics of companion diagnostics based on existing economic evaluations of biomarker-guided therapies in cancer. METHODS: A literature search was performed using Medline, Embase, EconLit, Cochrane library for economic evaluations of biomarker-guided therapies with companion diagnostics in cancer. Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Studies were selected using pre-specified eligibility criteria based on the PICO framework. To make the included studies more comparable, we qualitatively synthesized the data under nine domains of methods where consensus was deemed lacking. RESULTS: Only four of the twenty-two studies included in this review were found to be of good quality with respect to incorporating the characteristics of companion biomarkers in economic evaluations. However, many evaluations focused on a pre-selected patient group rather than including all patients regardless of their biomarker status. Companion biomarker characteristics captured in evaluations were often limited to the cost or the accuracy of the test. Often, only the costs of biomarker testing were modelled. Clinical outcomes and health state utilities were often not included due to the limited data generated by clinical trials. Methods of economic evaluation were not applied consistently in assessments of companion cancer biomarkers for targeted therapies. It was also shown that conflicting cost-effectiveness results were likely depending on what comparator arm was chosen and what comparison structure was designed in the model. CONCLUSION: We found no consistent approach applied in assessing the value of companion biomarker tests and including the characteristics of biomarkers in an economic evaluation of targeted oncology therapies. Currently, many economic evaluations fail to capture the full value of companion biomarkers beyond sensitivity/specificity and cost related to biomarker testing.

Cost-effectiveness analyses of targeted therapy and immunotherapy for advanced non-small cell lung cancer in the United States: a systematic review.

Introduction: Mutation-targeting and immuno-oncology drugs are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). Cost-effectiveness analyses (CEA) of these drugs have been conducted using various analytical methods and cost-effectiveness thresholds. This systematic review provides a comprehensive summary of the available evidence.Area covered: PubMed, Embase, and Cochrane Library were used to select for CEA of targeted therapies for NSCLC in the United States published between 2008 and 2020. Among the 28 included studies, a majority were published from 2017 to 2020 (n = 18) and more than half targeted non-squamous NSCLC (n = 15). The most frequently evaluated therapy was pembrolizumab (n = 11), followed by bevacizumab (n = 8) and erlotinib (n = 4). After 2009, all included studies applied $100,000 or more thresholds. Thresholds of studies supported by industry (median = $150,000) were more distributed than those of studies supported by nonprofits (median = $100,000).Expert commentary: Medications of interest have changed and are individualized to particular mutations. The cost-effectiveness thresholds varied among sponsors but generally trended to increase over time. This review provides an overview of the available cost-effectiveness findings for stakeholders and contributes to evidence-based practice.

Health services costs for lung cancer care in Australia: Estimates from the 45 and Up Study.

BACKGROUND: Of all cancer types, healthcare for lung cancer is the third most costly in Australia, but there is little detailed information about these costs. Our aim was to provide detailed population-based estimates of health system costs for lung cancer care, as a benchmark prior to wider availability of targeted therapies/immunotherapy and to inform cost-effectiveness analyses of lung cancer screening and other interventions in Australia. METHODS: Health system costs were estimated for incident lung cancers in the Australian 45 and Up Study cohort, diagnosed between recruitment (2006-2009) and 2013. Costs to June 2016 included services reimbursed via the Medicare Benefits Schedule, medicines reimbursed via the Pharmaceutical Benefits Scheme, inpatient hospitalisations, and emergency department presentations. Costs for cases and matched, cancer-free controls were compared to derive excess costs of care. Costs were disaggregated by patient and tumour characteristics. Data for more recent cases identified in hospital records provided preliminary information on targeted therapy/immunotherapy. RESULTS: 994 eligible cases were diagnosed with lung cancer 2006-2013; 51% and 74% died within one and three years respectively. Excess costs from one-year pre-diagnosis to three years post-diagnosis averaged ~$51,900 per case. Observed costs were higher for cases diagnosed at age 45-59 ($67,700) or 60-69 ($63,500), and lower for cases aged ≥80 ($29,500) and those with unspecified histology ($31,700) or unknown stage ($36,500). Factors associated with lower costs generally related to shorter survival: older age (p<0.0001), smoking (p<0.0001) and unknown stage (p = 0.002). There was no evidence of differences by year of diagnosis or sex (both p>0.50). For 465 cases diagnosed 2014-2015, 29% had subsidised molecular testing for targeted therapy/immunotherapy and 4% had subsidised targeted therapies. CONCLUSIONS: Lung cancer healthcare costs are strongly associated with survival-related factors. Costs appeared stable over the period 2006-2013. This study provides a framework for evaluating the health/economic impact of introducing lung cancer screening and other interventions in Australia.

Dose Escalation Assessment Among Targeted Immunomodulators in the Management of Inflammatory Bowel Disease.

BACKGROUND: The need for individualized treatment regimens is becoming more important in the management of patients with inflammatory bowel disease (IBD). Gastroenterologists may dose adjust either by increasing the dose or shortening the dosing interval from the initial recommended maintenance dose to achieve an appropriate clinical response. Understanding the role of dose escalation in the treatment of IBD in clinical practice provides payers in the United States insight into the real-world cost-effectiveness of targeted immunomodulators (TIMs) in the management of IBD. OBJECTIVE: To assess the prevalence and magnitude of dose escalation for approved IBD therapies. METHODS: Using the Source Healthcare Analytics database, patients with IBD who initiated treatment with a drug of interest from July 2015 to June 2017 were identified. Patient utilization of the TIMs was tracked for 12 months following initiation. All included patients had at least 2 diagnoses for ulcerative colitis or Crohn disease before TIM initiation and at least 5 claims for a drug of interest within the 12 months following initiation. Dose escalation was defined as an increase of at least 30% in the average daily dose (ADD) relative to the patient's expected maintenance dose on 2 consecutive prescriptions. The proportion of patients with dose escalation in the first 12 months after treatment initiation was determined. The magnitude of dose escalation was determined by calculating the patient's ADD across all noninduction dose claims and comparing it with the expected daily dose. Dose escalation prevalence and magnitude were used to quantify the equivalent patient treatment rate representing the number of patients per 100 that could have been treated with standard dosing, given the prevalence of dose escalation in the treated population. RESULTS: 7,028 patients (2,406 infliximab, 1,966 adalimumab, 1,745 vedolizumab, 472 ustekinumab, 285 certolizumab pegol, and 154 golimumab) met eligibility criteria and were included in the study. Among IBD therapies, dose escalation occurred most frequently with infliximab (39%), followed by adalimumab (28%), vedolizumab (23%), ustekinumab (22%), certolizumab pegol (20%), and golimumab (14%). The magnitude of dose escalation was greatest for ustekinumab (131%), followed by infliximab (70%), vedolizumab (62%), adalimumab (59%), certolizumab pegol (50%), and golimumab (45%). The calculated patient equivalence was highest for infliximab (128) and ustekinumab (128) compared with adalimumab (116), vedolizumab (114), certolizumab pegol (110), and golimumab (106). CONCLUSIONS: Among patients with IBD, dose escalation occurred with all TIMs examined with varying degrees of prevalence and magnitude. Real-world utilization patterns of TIMs indicate that dose escalation is an important part of the clinical management of IBD and needs to be considered when evaluating the cost-effectiveness of IBD treatments. DISCLOSURES: Financial support for this study was provided by AbbVie, which participated in study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Ehrenberg and McDonald are employees of IQVIA, which received funding from AbbVie to participate in this research. Griffith and Theigs are employed by AbbVie and may own stock or stock options in AbbVie.

Cost-Effectiveness Analysis of Baseline Testing for Resistance-Associated Polymorphisms to Optimize Treatment Outcome in Genotype 1 Noncirrhotic Treatment-Naïve Patients With Chronic Hepatitis C Virus.

OBJECTIVES: Direct-acting antivirals containing nonstructural protein 5A (NS5A) inhibitors administered over 8 to 12 weeks are effective in ∼95% of patients with hepatitis C virus. Nevertheless, patients resistant to NS5A inhibitors have lower cure rates over 8 weeks (<85%); for these patients, 12 weeks of treatment produces cure rates greater than 95%. We evaluated the lifetime cost-effectiveness of testing for NS5A resistance at baseline and optimizing treatment duration accordingly in genotype 1 noncirrhotic treatment-naïve patients from the perspective of the UK National Health Service. METHODS: A decision-analytic model compared (1) standard 12-week treatment (no testing), (2) shortened 8-week treatment (no testing), and (3) baseline testing with 12-/8-week treatment for those with/without NS5A polymorphisms. Patients who failed first-line therapy were retreated for 12 weeks. Model inputs were derived from published studies. Costs, quality-adjusted life-years, and the probability of cost-effectiveness were calculated. RESULTS: Baseline testing had an incremental net monetary benefit (INMB) of £11 838 versus standard 12 weeks of therapy (no testing) and low probability (31%) of being the most cost-effective, assuming £30 000 willingness to pay. Shortened 8 weeks of treatment (no testing) had an INMB of £12 294 and the highest probability (69%) of being most cost-effective. Scenario analyses showed baseline testing generally had the highest INMB and probability of being most cost-effective if first- and second-line drug prices were low (<£20k). CONCLUSIONS: Optimizing treatment duration based on NS5A polymorphisms for genotype 1 noncirrhotic treatment-naive patients in the United Kingdom is not cost-effective if the drug costs are high; the strategy is generally most cost-effective when drug prices are low (<£20k).

Economic Evaluation of Systemic Treatments for Advanced Melanoma: A Systematic Review.

BACKGROUND: Many high cost treatments for advanced melanoma have become available in recent years. National health technology assessment agencies have raised concerns regarding uncertainty in their clinical and cost-effectiveness. OBJECTIVE: The aim of this systematic review is to identify economic evaluations of treatments for advanced melanoma and review model assumptions, outcomes, and quality as preparation for a health technology assessment. METHODS: A search of Embase, MEDLINE, EconLit, and the Cochrane Database was conducted. Only studies using decision-analytic models were included. Two authors independently completed full-text review and data extraction. RESULTS: Fifteen studies were identified. There were major differences in the structural assumptions underpinning the models. There was general agreement in study conclusions, although the predicted costs and quality-adjusted life years for each treatment varied. BRAF monotherapy (vemurafenib, dabrafenib) or BRAF/MEK combination therapy (BRAF monotherapy with cobimetinib or trametinib) has not been shown to be cost-effective in any jurisdiction. PD-1 inhibitors (pembrolizumab, nivolumab) are consistently found to be cost-effective compared with ipilimumab, although their cost-effectiveness compared with chemotherapy is not established. Combination therapy with nivolumab and ipilimumab is unlikely to be cost-effective in any setting. One study including all agents found that none of the new treatments were cost-effective relative to chemotherapy. Publication of the study in a health economics journal is associated with better reporting of and higher-quality assessment than those published in clinical journals. CONCLUSION: Despite differences in model structures and assumptions, the conclusions of most included studies were consistent. Health technology assessment has a key role in maximizing value from high-cost innovative treatments. Consideration should be given to divestment from BRAF/MEK inhibitors and ipilimumab in favor of reimbursement of PD-1 inhibitors.

Impact of the biomarker enrichment strategy in drug development.

INTRODUCTION: Recently, new oncology therapies were developed using a biomarker for patient selection. In the era of cancer genomics, this paradigm is expected to increase. Most cytotoxic chemotherapies and other oncological treatments were historically approved without a biomarker. However, this strategy seems to be less efficient. We reviewed the biomarker-based strategy and its impact in cancer drug development. AREAS COVERED: Oncology drugs approval rates are low and most of the drugs that failed to be approved were in late stages of development. In addition to that, attrition rates are high. The use of biomarkers in drug development has shown higher response rates, longer progression-free survival rates and even higher overall survival rates. Hence, the biomarker-based strategy seems to be associated with more successful drug programs, including a shorter timeline and higher likelihood of success. EXPERT OPINION: Even though the development of biomarker-driven strategies is promising, there are some challenges surrounding this field of study, such as reducing the cost of drug development, enhancing the technique of biomarkers identification (aiming more specific biomarkers and considering tumor heterogeneity) and exploring the role of next-generation sequencing tests in drug development. Also, collaboration between clinicians, scientists and regulatory agencies is fundamental.

Comprehensive value assessment of drugs using a multi-criteria decision analysis: An example of targeted therapies for metastatic colorectal cancer treatment.

OBJECTIVE: This study is aimed toward establishing a decision-making model with multiple criteria for appraisal and reimbursement to compare the attitudes of different stakeholders toward various dimensions and criteria and to evaluate the five targeted therapies (bevacizumab, cetuximab, panitumumab, aflibercept, and regorafenib) for metastatic colorectal cancer. METHOD: This study is a multi-criteria decision analysis (MCDA) using a model that includes three dimensions and nine criteria. Both the overall and individual scores of the respective targeted therapies in different dimensions and criteria were calculated. A sensitivity analysis was carried out in order to evaluate the robustness of the research results. An interview-based questionnaire survey was applied to obtain the performance information for the targeted therapies and the weights of the dimensions and criteria. RESULTS: Overall, the clinical dimension had the highest weight, followed by the economic dimension, and finally, the social dimension. In the clinical dimension, the "comparative efficacy" criterion had the highest weight; in the economic dimension, the "cost-effectiveness" criterion" was given the greatest importance; in the social dimension, the "social concern and patient needs" criterion was given more emphasis. The overall values ranked from high to low as follows: cetuximab (overall score 3.3666), bevacizumab (3.3043), panitumumab (3.2030), aflibercept (2.8923) and regorafenib (2.8366). CONCLUSIONS: A comprehensive value assessment system combining "multi-dimensional criteria," "multi-perspectives," and an "integrative assessment" is necessary to evaluate the value of medicines. The results showed not only the order of weights of different dimensions or criteria, but also the rankings of the value of the targeted therapies.

Potential life years not saved due to lack of access to anti-EGFR tyrosine kinase inhibitors for lung cancer treatment in the Brazilian public healthcare system: Budget impact and strategies to improve access. A pharmacoeconomic study

ABSTRACT BACKGROUND: Lung cancer is the fourth most common cancer in Brazil. In the 2000s, better understanding of molecular pathways led to development of epidermal growth factor receptor (EGFR)-targeted treatments that have improved outcomes. However, these treatments are unavailable in most Brazilian public healthcare services (Sistema Único de Saúde, SUS). OBJECTIVE: To assess the potential number of years of life not saved, the budget impact of the treatment and strategies to improve access. DESIGN AND SETTING: Pharmacoeconomic study assessing the potential societal and economic impact of adopting EGFR-targeted therapy within SUS. METHODS: We estimated the number of cases eligible for treatment, using epidemiological data from the National Cancer Institute. We used data from a single meta-analysis and from the Lung Cancer Mutation Consortium (LCMC) study as the basis for assessing differences in patients' survival between use of targeted therapy and use of chemotherapy. The costs of targeted treatment were based on the national reference and were compared with the amount reimbursed for chemotherapy through SUS. RESULTS: There was no life-year gain with EGFR-targeted therapy in the single meta-analysis (hazard ratio, HR, 1.01). The LCMC showed that 1,556 potential life-years were not saved annually. We estimated that the annual budget impact was 125 million Brazilian reais (BRL) with erlotinib, 48 million BRL with gefitinib and 52 million BRL with afatinib. Their incremental costs over chemotherapy per life-year saved were 80,329 BRL, 31,011 BRL and 33,225 BRL, respectively. A drug acquisition discount may decrease the budget impact by 30% (with a 20% discount). A fixed cost of 1,000 BRL may decrease the budget impact by 95%. CONCLUSION: Reducing drug acquisition costs may improve access to EGFR-targeted therapy for lung cancer.

Analysis of the cost-effectiveness of treatment strategies for CML with incorporation of treatment discontinuation.

The cost of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) is a substantial economic burden. In Japan, imatinib, dasatinib, and nilotinib are now approved as first-line treatment of CML in chronic phase. Recent "stop TKI" trials have shown that TKIs can be safely discontinued in nearly one-half of patients with sustained deep molecular response (DMR). In this study, we analyzed the cost-effectiveness of a simulated 10 years of CML treatment including stop TKI in both the United States and Japan. We constructed Markov models to compare 4 strategies in which treatment was initiated with imatinib, dasatinib, nilotinib, or any of these TKIs at the physician's discretion. Treatment was switched to another TKI in the case of intolerance or resistance to the initial TKI, and TKIs were discontinued if DMR persisted for 2 years. "Imatinib first" offered 7.34 quality-adjusted life years (QALYs) at the cost of $1 022 148 in the United States (US dollars) and ¥32 526 785 in Japan (Japanese yen). In comparison with imatinib first, the incremental cost-effectiveness ratio per QALY of "dasatinib first" (7.68 QALY, $1 236 052, ¥51 506 254), "nilotinib first" (7.64 QALY, $1 245 667, ¥39 635 598), and "physician's choice" (7.55 QALY, $1 167 818, ¥41 187 740) was $641 324, $696 717, and $666 634 in the United States and ¥54 456 325, ¥23 154 465, and ¥39 635 615 in Japan, respectively. None of the 3 strategies met the willingness-to-pay threshold. The results were robust to univariate and multivariate sensitivity analyses. Imatinib first was shown to be the most cost-effective approach even with the incorporation of stop TKI.

Cost-effectiveness of New Targeted Agents in the Treatment of Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is clinically heterogeneous. Integration of oral targeted therapies (OTTs) in the management of CLL has fundamentally altered CLL treatment pathways and improved outcomes for patients with CLL.We review the cost-effectiveness of OTTs in the treatment of CLL. We used MeSH (Medical Subject Heading) terms and keywords to search the National Library of Medicine online MEDLINE database (PubMed) for articles related to cost-effectiveness of OTTs in CLL care.Oral targeted therapies add considerable expense to the treatment of CLL for patients and the health care system. Cost-effectiveness analyses of OTTs are not uniform in their conclusions and depend on patient groups selected for analysis. Given the substantial increase in expense associated with integration of OTTs in CLL treatment, cost reduction methods are needed to ensure equitable access to novel therapies for all patients with CLL.

Economic evaluations of oral medications for breast cancer treatment in the U.S.: a systematic review with a focus on cost-effectiveness threshold.

Introduction: With the advent of targeted therapy, the U.S. Food and Drug Administration has recently approved several oral anticancer medications (OAMs) for breast cancer (BC). Despite the improved effectiveness of those OAMs, the high financial burden is an issue. Evidence from cost-effectiveness analysis (CEA) can provide valuable information for decision-makers when deciding whether to use these high-priced medications. Many CEAs on OAMs have been conducted using various analytical approaches and cost-effectiveness thresholds (CETs). However, there is no comprehensive systematic review of CEAs across all OAMs.Area covered: PubMed and Cochrane library were used to select for CEAs of OAM for BC in the U.S. published by May 2019. Among the 25 included studies, studies published between 1993 and 2011 analyzed either early BC (n = 11) or advanced/metastatic BC (n = 5), those between 2012-2019 analyzed advanced/metastatic BC (n = 9). Studies including targeted therapies were published after 2009. The CETs tended to increase over time and were higher in the studies for advanced/metastatic BC (median = $125,000) than those for early BC (median = $50,000).Expert commentary: The target population and medications of interest have changed and the methods of articles have evolved. The range of CETs tends to differ by study setting with an increase over time.

Cost burden of diffuse large B-cell lymphoma.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and is a clinically heterogeneous disease. Treatment pathways for DLBCL are diverse and integrate established and novel therapies.Areas covered: We review the cost burden of DLBCL and the cost-effectiveness of DLBCL management including precision and cellular medicine. We utilized Medical Subject Heading (MeSH) terms and keywords to search the National Library of Medicine online MEDLINE database (PubMed) for articles related to cost, cost burden, and cost-of-illness of DLBCL and cost-effectiveness of DLBCL management strategies published in English as of June 2019.Expert commentary: Available and developing DLBCL therapies offer improved outcomes and often curative treatment at considerable financial expense, and the total cost burden for DLBCL management is substantial for patients and the healthcare system. In the era of personalized medicine, CAR T cells and targeted therapies provide exciting avenues for current and future DLBCL care and can further increase treatment cost. Determinations of cost and cost-effectiveness in DLBCL treatment pathways should continue to guide care providers and systems in identifying cost reduction strategies to provide appropriate therapies to the greatest number of patients in treating DLBCL.

Economics of New Molecular Targeted Personalized Radiopharmaceuticals.

Nuclear medicine has come a long way since 2007 when Adrian Nunn pointed out the approval of radiopharmaceuticals was at an all-time low with all the major radiopharmaceutical agents in use having been approved over 10 years ago. Challenges being the prohibitively high cost of drug development and the large number of drugs failing in clinical trials. Proceed to today where molecular imaging is fast-tracking the drug discovery process by reducing both the time and cost to screen candidates by quantitating the drugs effect on the target and toxicity to normal tissues. Nuclear medicine is now leading medical practice in personalized medicine using the theragnostic approach. Theragnostics is defined as the use of molecular diagnostic techniques in real time to stratify patients to guide treatment decisions such as the choice of drug, the dose of administration, and the timing of drug delivery for a given patient. Enabling visualization and quantitation of in vivo function of the whole body and thus patient heterogeneity and variability informs the physician on how to treat an individual patient. Recent successes such as the Food and Drug Administration approval of Lutathera and NETSPOT have resulted in an increasing number of pharmaceutical companies pursing theragnostics further heightened by the purchase of Advanced Accelerator Applications for 3.9 billion by Novartis and Endocyte, Inc for 2.1 billion. Theragnostics are further aiding drug development by showing which agents are most viable and reducing the overall cost of bringing a drug to clinical trials and regulatory approval. This is indeed a renaissance for nuclear medicine in which the acceptance of imaging to inform and monitor therapy has been embraced and even required by the Food and Drug Administration for the clinical evaluation of targeted therapeutic radiopharmaceuticals showing there is indeed a viable business model for targeted theragnostic radiopharmaceuticals and personalized medicine.

Challenges in the value assessment, pricing and funding of targeted combination therapies in oncology.

BACKGROUND: The use of targeted combination therapy (TCT) is becoming the standard of care in oncology as cancers are attacked through multiple inhibition mechanisms. TCTs pose a budget challenge to health systems and an economic return challenge for companies developing them. METHODS: We conducted a systematic literature review to identify challenges specific to TCTs and reviewed publicly available reports by health technology assessment and pricing and reimbursement bodies. We synthesized our findings into a problem map. RESULTS AND DISCUSSION: Challenges and policy solutions linked to TCTs remain almost fully unexplored; we identified few resources that explicitly addressed TCTs. Contributors to the budget challenge are found at different layers; they and include static willingness-to-pay (WTP) for TCTs and inefficiencies in managing prices of backbone therapies. Economic return challenges are related to payer-imposed restrictions, peculiarities of TCT development, and conflicting incentives of pharmaceutical companies that own constituent therapies. Consequences are delayed or restricted patient access to TCTs, disincentives for research and development, and fewer life years gained. CONCLUSIONS: Multiple issues will lead to the unsustainability of funding systems and possible conflict between stakeholders around access to TCTs. To manage these, new value assessment and attribution methodologies, modified trial designs and differentiated WTP thresholds can be considered in ways that are customized to the characteristics of different health systems.