Clinical and cost implications of amyloid beta detection with amyloid beta positron emission tomography imaging in early Alzheimer’s disease – the case of florbetapir

<p><b>Objective:</b> Amyloid beta (Aβ) positron emission tomography (PET) imaging helps estimate Aβ neuritic plaque density in patients with cognitive impairment who are under evaluation for Alzheimer’s disease (AD). This study aims to evaluate the cost-effectiveness of the Aβ-PET scan as an adjunct to standard diagnostic assessment for diagnosis of AD in France, using florbetapir as an example.</p> <p><b>Methods:</b> A state-transition probability analysis was developed adopting the French Health Technology Assessment (HTA) perspective per guidance. Parameters included test characteristics, rate of cognitive decline, treatment effect, costs, and quality of life. Additional scenarios assessed the validity of the analytical framework, including: (1) earlier evaluation/treatment; (2) cerebrospinal fluid (CSF) as a comparator; and (3) use of other diagnostic procedures. Outputs included differences in quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). All benefits and costs were discounted for time preferences. Sensitivity analyses were performed to assess the robustness of findings and key influencers of outcomes.</p> <p><b>Results:</b> Aβ-PET used as an adjunct to standard diagnostic assessment increased QALYs by 0.021 years and 10 year costs by €470 per patient. The ICER was €21,888 per QALY gained compared to standard diagnostic assessment alone. When compared with CSF, Aβ-PET costs €24,084 per QALY gained. In other scenarios, Aβ-PET was consistently cost-effective relative to the commonly used affordability threshold (€40,000 per QALY). Over 95% of simulations in the sensitivity analysis were cost-effective.</p> <p><b>Conclusion:</b> Aβ-PET is projected to affordably increase QALYs from the French HTA perspective per guidance over a range of clinical scenarios, comparators, and input parameters.</p

An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population

<div><p>Objective</p><p>Analyze the economic value of replacing conventional fetal aneuploidy screening approaches with non-invasive prenatal testing (NIPT) in the general pregnancy population.</p><p>Methods</p><p>Using decision-analysis modeling, we compared conventional screening to NIPT with cell-free DNA (cfDNA) analysis in the annual US pregnancy population. Sensitivity and specificity for fetal aneuploidies, trisomy 21, trisomy 18, trisomy 13, and monosomy X, were estimated using published data and modeling of both first- and second trimester screening. Costs were assigned for each prenatal test component and for an affected birth. The overall cost to the healthcare system considered screening costs, the number of aneuploid cases detected, invasive procedures performed, procedure-related euploid losses, and affected pregnancies averted. Sensitivity analyses evaluated the effect of variation in parameters. Costs were reported in 2014 US Dollars.</p><p>Results</p><p>Replacing conventional screening with NIPT would reduce healthcare costs if it can be provided for $744 or less in the general pregnancy population. The most influential variables were timing of screening entry, screening costs, and pregnancy termination rates. Of the 13,176 affected pregnancies undergoing screening, NIPT detected 96.5% (12,717/13,176) of cases, compared with 85.9% (11,314/13,176) by conventional approaches. NIPT reduced invasive procedures by 60.0%, with NIPT and conventional methods resulting in 24,596 and 61,430 invasive procedures, respectively. The number of procedure-related euploid fetal losses was reduced by 73.5% (194/264) in the general screening population.</p><p>Conclusion</p><p>Based on our analysis, universal application of NIPT would increase fetal aneuploidy detection rates and can be economically justified. Offering this testing to all pregnant women is associated with substantial prenatal healthcare benefits.</p></div

Model inputs and economic value of NIPT for fetal aneuploidy screening.

<p>FP(s), false positives; CVS, chorionic villus sampling; NIPT, non-invasive prenatal testing</p><p>^{^} NIPT values that correspond to the range applied to each input variable. These values can be compared to the $744 value assigned to the set of baseline model inputs.</p><p>^¥ Alternative scenario showing results when all initial screening is performed in the second trimester.</p><p>* Baseline invasive testing rates for true positives were 73$369) was a buildup of all the individual components (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132313#sec007" target="_blank">Results</a>).</p><p>^§ The range of lifetime costs of an affected child was baseline ±20%; the upper and lower range values for each indication were modified together.</p><p>^˅Most of the variability is attributable to lifetime costs for Down syndrome (see text).</p><p>Model inputs and economic value of NIPT for fetal aneuploidy screening.</p

Aneuploidy incidence rates and performance of conventional screening approaches in the first and second trimester for a general population.

<p>^{^} Conventional screening based on maternal age, nuchal translucency, maternal serum pregnancy-associated plasma protein A [PAPPA] and free beta human chorionic gonadotropin [hCG] at 12 weeks gestational age.</p><p>* NIPT sensitivity and specificity was based on pooled data from 19 published studies (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132313#pone.0132313.s003" target="_blank">S2 Table</a>); NIPT sensitivity and specificity was considered to be independent of pregnancy stage and maternal prior risk.</p><p>^† First trimester sensitivity for trisomy 13 screening is based on the algorithm developed for trisomy 18 screening [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132313#pone.0132313.ref030" target="_blank">30</a>].</p><p>^‡ Second trimester sensitivity for trisomy 13 screening is assumed to be equal to the proportion of trisomy 13 affected pregnancies serendipitously identified as a false positive in Down syndrome and trisomy 18 screening.</p><p>^§ No specific screening protocols exist for trisomy 13 and monosomy X.</p><p>Aneuploidy incidence rates and performance of conventional screening approaches in the first and second trimester for a general population.</p

Patient and tumor characteristics.

<p>Patient and tumor characteristics.</p

Adjuvant treatment recommendation pre- and post-Prosigna test results, by Prosigna test risk category.

<p>Adjuvant treatment recommendation pre- and post-Prosigna test results, by Prosigna test risk category.</p

Intrinsic tumor subtype results by physician judgement and Prosigna test results.

<p>Intrinsic tumor subtype results by physician judgement and Prosigna test results.</p

Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer

<p>Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice.</p> <p>A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient’s ROR. Patients completed questionnaires on decision-making, anxiety, and health status.</p> <p>Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (<i>p</i> < 0.05).</p> <p>Though this study does not include evaluation of the impact of GEP on long-term outcomes, it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection. Patients’ anxiety about the selected adjuvant therapy decreased with use of the GEP.</p