scholarly journals More Unnecessary Imaginary Worlds – Part 4: The ICER Evidence Report for Crizanlizumab, Voxelotor and L-Glutamine for Sickle Cell Disease

2020 ◽  
Vol 11 (2) ◽  
pp. 4
Author(s):  
Paul Langley
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lifetime Cost ◽  
Value Assessment ◽  
Assessment Framework ◽  
Cell Disease ◽  
Reference Case ◽  
The Past ◽  
Article Type ◽  
Utility Scale

A number of commentaries have been published over the past 4 years by the present author on the manifest flaws in the reference case value assessment framework of the Institute for Economic and Clinical Review. The recent release of the evidence report on sickle cell disease continues ICER’s commitment to what has been described as the creation of imaginary worlds to support value assessment. The purpose of the present commentary is to continue the critiques that have been presented for earlier evidence reports. This is important because of the apparent willingness to take ICER’s recommendations at face value rather than a critical review of the value assessment framework. The case presented here points to a  number of weaknesses in the ICER framework: (i) the fabrication of imaginary constructs with a lifetime cost-per-incremental QALY framework; (ii) the consequent failure to meet the standards of normal science; (iii) the illogical reliance of assumptions drawn from the literature to create future scenarios; (iv) the rejection of hypothesis testing in favor of  ‘approximate information’ and (v) a belief that in the construction of QALYS that the EQ-5D-3L utility scale has ratio properties. This last point is demonstrably false which means that the ICER value assessment framework collapses. It is impossible mathematically, a failure to meet the axioms of fundamental measurement, for an ordinal utility scale to be combined with time spent in a disease state. The result is that the pricing and access recommendations for Crizanlizumab, Voxelotor and L-glutamine in sickle cell disease (SCD) are complete nonsense and should be rejected.   Article Type: Commentary

Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 362-369 ◽  
Author(s):  
Deepa Manwani ◽  
Paul S. Frenette
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Targeted Therapies ◽  
Therapeutic Intervention ◽  
Fetal Hemoglobin ◽  
Cell Disease ◽  
The Past ◽  
Symptomatic Management

Abstract Recurrent and unpredictable episodes of vaso-occlusion are the hallmark of sickle cell disease. Symptomatic management and prevention of these events using the fetal hemoglobin–reactivating agent hydroxyurea are currently the mainstay of treatment. Discoveries over the past 2 decades have highlighted the important contributions of various cellular and soluble participants in the vaso-occlusive cascade. The role of these elements and the opportunities for therapeutic intervention are summarized in this review.

Procedures, Pain, and Parents

PEDIATRICS ◽  
1991 ◽  
Vol 87 (4) ◽  
pp. 563-565
Author(s):  
HOWARD BAUCHNER
Keyword(s):  
Sickle Cell Disease ◽  
Lumbar Puncture ◽  
Sickle Cell ◽  
Acute Pain ◽  
Cell Disease ◽  
Emergency Rooms ◽  
Pharmacological Agents ◽  
The Past ◽  
The Subject

During the past decade certain types of pain in children have been the subject of much research and discussion. The pain associated with cancer, sickle cell disease, and the preoperative and post-operative periods have all been extensively studied and reviewed.1-4 Less information is available about acute pain inflicted in emergency rooms. Children commonly undergo procedures such as venipuncture, intravenous cannulation, lumbar puncture, and manipulation of fractures in emergency rooms without the benefit of any analgesia. What techniques are available to reduce the pain and anxiety that children feel when they undergo procedures? Traditionally, physicians have tried to reduce pain by using pharmacological agents.

Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies

PEDIATRICS ◽  
1989 ◽  
Vol 83 (5) ◽  
pp. 813-814
Author(s):  
DORIS WETHERS ◽  
HOWARD PEARSON ◽  
MARILYN GASTON
Keyword(s):  
Sickle Cell Disease ◽  
Early Diagnosis ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Case Fatality ◽  
The United States ◽  
Early Mortality ◽  
Cell Disease ◽  
Newborn Period ◽  
The Past

Hemoglobinopathies represent one of the major health problems in the United States and constitute the most common genetic disorders in some populations. Sickle cell disease (SS, SC, S-β-thalassemia) alone affects about one in 400 American black newborns, as well as persons of African, Mediterranean, Asian, Caribbean, Middle Eastern, and South and Central American origins. For the past 20 years, the medical profession has known that children with sickle cell anemia have an increased susceptibility to severe bacterial infection, particularly due to Streptococcus pneumoniae. The risk of major infection and death posed by this organism is greatest in the first 3 years of life and can occur as early as 3 months of age. In fact, this infection may be the first clinical manifestation of disease. The infection can be fulminant, progressing from the onset of fever to death in a matter of hours, and the case fatality rate is reported as high as 30%. In addition, acute splenic sequestration, another acute catastrophic event, contributes to early mortality in children with sickle cell anemia and may occur as early as 5 months of age. It has been proposed that early diagnosis to identify infants with major sickle hemoglobinopathies, who have a high risk of early mortality and morbidity, is essential to institute appropriate ongoing care and effective measures of prophylaxis and intervention. Early diagnosis of hemoglobinopathies should be in the newborn period. Even though the technology to screen infants in the newborn period has been available for the past 15 to 20 years, screening has not received widespread acceptance.

Predictors of Mortality in Children and Adolescents with Sickle Cell Disease: The PUSH Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 515-515 ◽  
Author(s):  
Mehdi Nouraie ◽  
Sohail R. Rana ◽  
Oswaldo L Castro ◽  
Lori Luchtman-Jones ◽  
Craig Sable ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Children And Adolescents ◽  
Sickle Cell ◽  
Severe Pain ◽  
Blood Transfusions ◽  
Cell Disease ◽  
Risk Of Death ◽  
The Past ◽  
History Of

Abstract Abstract 515 Background: Recent studies indicate that the disease-specific mortality In sickle cell anemia is about 6% in children up to 18 years and 15% in the 18–30 year age group, yielding a cumulative mortality of 21% by age 30 years. It is important to identify children at high risk so that early interventions can be developed to reduce this high mortality. Methods: We prospectively enrolled 505 children and adolescents with sickle cell disease in 2005–2010, 380 with hemoglobin SS and 130 with other genotypes. The median age at enrollment was 12 years with a range of 3 to 20 years. Baseline clinical features, echocardiography, six-minute walk test and pulmonary function testing were performed at steady-state. Follow-up for mortality has been performed in 470 of the participants at a median of 37 months after enrollment, range of 1 to 59 months. Results: Six of 470 patients (1.3%) died during the follow-up period, five with hemoglobin SS and one with hemoglobin SC. The median age at the time of death in these six participants was 20 years, range of 15 to 23 years. Death occurred during the follow-up period in 2.7% of participants over 12 years of age at enrollment and 3.7% of those over 15 years of age. The causes of death were stroke in 4, multiorgan failure in 1 and unknown in 1. Death occurred in 5.9% of 51 participants with a history of stroke versus 0.7% of 416 without stroke history; in 3.5% of 113 participants with a history of asthma versus 0.6% of 354 without asthma history; in 4.9% of 103 participants with 10 or more blood transfusions lifetime versus 0.3% of 359 with less than 10 blood transfusions; in 3.3% of 90 participants with two or more severe pain episodes in the past year versus 0.8% of 380 participants with less than two severe pain episodes in the past year. In age-adjusted analyses, the hazards ratio (95% CI) of death was 6.1 (1.2-30.5) for history of stroke (P=0.029), 10.2 (1.2-89.5) for history of frequent blood transfusions (P=0.036), 5.8 (1.1-31.8) for history of asthma (P=0.044) and 1.07 (1.00-1.14) for frequent severe pain episodes (P=0.047). Clinical findings associated with these risk factors included higher concentrations of markers of hemolysis for history of stroke and history of frequent blood transfusions, decreased FEV1/FVC and increased total lung capacity for history of asthma, and lower concentrations of markers of hemolysis and high ECHO-determined tricuspid regurgitation velocity for history of frequent severe pain episodes. Conclusions: Over a median of three years of observation of this cohort, no deaths occurred among 248 sickle cell disease children 12 years of age or younger at enrollment but there were 6 deaths among 222 participants 13–20 years of age at enrollment. In bi-variate age-adjusted analyses, histories of stroke, asthma, frequent blood transfusions and frequent pain episodes were associated with an increased risk of death. Strikingly, four of the five deaths in which the cause was known were due to stroke. The present data on mortality in the PUSH study suggest that prevention of stroke is critical in improving the survival in adolescents and young adults with sickle cell disease. Disclosures: No relevant conflicts of interest to declare.

Low-Dose Ketamine Infusion In Adult Patients With Sickle Cell Disease – Impact On Management Of Acute Painful Episodes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2249-2249
Author(s):  
Michel Gowhari ◽  
Aileen Chu ◽  
Julie Golembiewski ◽  
Robert E. Molokie
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Pain Control ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Adult Patients ◽  
Cell Disease ◽  
Ketamine Infusion ◽  
The Past ◽  
Painful Episode

Abstract Introduction Acute painful (vaso-occlusive) episode is the clinical hallmark of sickle cell disease (SCD). Individuals with SCD may experience acute episodes of severe debilitating pain that requires an acute care/emergency room visit and/or hospitalization. While parenteral opioids are the mainstay of treatment, the use of these agents may be complicated by toxicity, tolerance, and opioid-induced hyperalgesia. Additionally, using one medication/mode of treatment may be inadequate to achieve optimal safe pain control. Ketamine as an adjuvant treatment (administered in low sub-anesthetic doses) has been recognized for its utility in the management of a variety of painful conditions, ranging from oncologic to post-operative pain. However, there is limited literature supporting its use in treating acute sickle painful episodes. Here we have undertaken a retrospective analysis of adult patients with SCD who were treated with low-dose ketamine infusion during an acute painful episode in order to determine its effects of lowering opioid requirements. Methods A retrospective chart and database review was conducted on all patients with SCD who received low-dose ketamine infusion during an acute painful episode in the past three years at a single institution. After a review of inpatient pharmacy records, thirty unique subjects with SCD were identified to have received low-dose ketamine infusion during an acute painful episode in the past three years. For each of these subjects, total and daily (24hr) opioid requirements were determined for the admissions of a vaso-occlusive episode where ketamine infusion was used as an adjuvant for pain control and compared to the prior admission. For the ketamine admission, opioid requirements before, during, and after infusion were also compared. The opioid requirement was converted to intravenous morphine equivalents for standardized comparison. Total opioid and daily (24hr) requirements were determined for each admission. Results Full analysis of all thirty subjects (uncomplicated and complicated pain crises, ketamine infusion of any duration) revealed that the opioid requirement was significantly lower after ketamine compared to before ketamine was started (Wilcoxon signed-rank test P=0.029). The total opioid requirement during the entire ketamine admission, however, was not significantly different from the total opioid requirement during the non-ketamine admission (P=0.088). When a sub-analysis was performed on subjects receiving a ketamine infusion for greater than 24 hours (N=22), the 24hr opioid requirement was significantly lower after ketamine compared to before ketamine was started (P=0.0397). The total opioid requirement during the entire ketamine admission was not significantly different from the total opioid requirement during the non-ketamine admission (P=0.194). When a sub-analysis was performed on subjects with an uncomplicated vaso-occlusive episode (N=17), 24hr opioid requirement was significantly lower after ketamine compared to before ketamine was started (P=0.036). Additionally, the average daily opioid requirement throughout the entire ketamine admission was significantly lower than the average daily opioid requirement during the non-ketamine admission (P=0.001). The total opioid requirement during the entire ketamine admission was not significantly different from the total opioid requirement during the non-ketamine admission (P=1). For the full and subgroup analyses of opioid requirements during the ketamine admission, there was a significantly greater amount of opioid required before the ketamine was started compared to during and after ketamine infusion. Conclusion The use of low-dose infusion of ketamine as an adjuvant for pain control in patients with SCD during vaso-occlusive episode resulted in a significant decrease in opioid requirements. Hence it appears that a low-dose ketamine infusion has utility in the treatment of acute pain crises in adult patients with sickle cell disease. Disclosures: No relevant conflicts of interest to declare.

Microparticles As Biomarkers Of Osteonecrosis Of The Hip In Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2226-2226
Author(s):  
Anne M Marsh ◽  
Raymond Schiffelers ◽  
Ginny Gildengorin ◽  
Frans A Kuypers ◽  
Carolyn Hoppe
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Vascular Occlusion ◽  
Predictive Biomarker ◽  
Acute Chest Syndrome ◽  
Mobility Limitations ◽  
Cell Disease ◽  
The Past ◽  
D Dimer

Abstract Introduction Sickle cell disease (SCD) is the most common cause of osteonecrosis of the femoral head (ONFH) in children. ONFH is a debilitating condition that is associated with mobility limitations, chronic pain, and an impaired quality of life. While the mechanisms that cause ONFH remain unknown, ischemia from recurrent microvascular occlusion is likely to play a role. Vascular occlusion may result directly from obstruction by sickled cells, or indirectly via complex interdependent pathways characterized by sustained endothelial activation, chronic inflammation, and coagulation. Microparticles (MP) are small, cell membrane-derived vesicles generated in response to cellular activation, injury or apoptosis. MPs have emerged as potential modulators of inflammation and thrombosis and have been found to be elevated in patients with ONFH in the general population. Objective This pilot study examined whether microparticle levels in patients with SCD who have ONFH differ from SCD patients without ONFH, as well as healthy African American (AA) controls. Methods Subjects were recruited at their baseline status and were excluded if they had been transfused within the past 30 days, hospitalized for a vaso-occlusive pain episode, acute chest syndrome, fever or surgery within the past 30 days, or had bony lesions of the femur or hip due to causes unrelated to SCD. For MP analysis, whole blood was collected in sodium citrate tubes and centrifuged for 15 minutes at 1500 x g at 20° C to generate platelet poor plasma. Aliquots of the plasma were immediately frozen and stored at -80° C until the time of MP analysis. 300 μl samples were diluted in PBS and centrifuged at 10000 x g for 1hr and the supernatant was centrifuged at 100,000 x g for 2 hr. The pellet was re-suspended in 1 mL of PBS and subjected to nanoparticle-tracking analysis to determine concentration and size. Additional laboratory biomarkers of inflammation and coagulation, including highly-sensitive C-reactive protein (hs-CRP), von Willebrand factor antigen (vWF Ag), tissue factor (TF), and D-dimer were analyzed for differences between groups. Analysis of variance was used to compare MP and biomarker levels between the three groups. The institutional review board at Children's Hospital & Research Center Oakland approved the study protocol and written informed consent was obtained from all participants. Results Characteristics of the 30 subjects enrolled are shown in Table I. Total microparticle levels in ONFH(+) patients were 2.3-fold higher than in ONFH(-) patients, and 2.5-fold higher than in AA controls (Figure 1). Mean MP levels for ONFH(+) patients, ONFH(-) patients, and AA controls were 4.55 x 1010, 1.99 x 1010, and 1.85 x 1010, respectively. Microparticle levels in ONFH(-) SCD patients did not differ from AA controls. There were no statistically significant differences in hsCRP, vWF Ag, TF, or D-dimer levels between the ONFH(-) and ONFH(+) groups. Conclusions The results of this study demonstrate significantly elevated MP levels in individuals with SCD who have ONFH. Additional studies are needed to better understand the mechanistic effects of MPs on the development of ONFH and to determine whether MP levels may be useful as a predictive biomarker for early disease detection. This publication was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Disclosures: No relevant conflicts of interest to declare.

Sickle Cell Disease

Hematology ◽  
2004 ◽  
Vol 2004 (1) ◽  
pp. 35-47 ◽  
Author(s):  
George R. Buchanan ◽  
Michael R. DeBaun ◽  
Charles T. Quinn ◽  
Martin H. Steinberg
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Short Chain Fatty Acids ◽  
Clinical Severity ◽  
Careful Study ◽  
Red Cell ◽  
Cell Disease ◽  
The Past ◽  
Hydroxyurea Treatment

Abstract Much progress has been made during the past several decades in gaining understanding about the natural history of sickle cell disease and management approaches aimed at treating or even preventing certain disease complications. The characterization of the human genome now offers the opportunity to understand relationships regarding how gene polymorphisms as well as how environmental factors affect the sickle cell disease phenotype, i.e., the individual patient’s overall clinical severity as well as their specific organ function. This chapter explores some of these recent advances in knowledge. In Section I, Dr. Michael DeBaun characterizes the problem of silent stroke in sickle cell disease, comparing and contrasting its clinical and neuroimaging features with overt stroke. Combined, these events affect virtually 40% of children with sickle cell anemia. New understanding of risk factors, associated clinical findings, and imaging technologies are impacting substantially on treatment options. The appreciable cognitive dysfunction and other sequelae of silent infarct demand more effective treatments and ultimate prevention. In Section II, Dr. Charles Quinn addresses the conundrum of why some patients with sickle cell disease do well whereas others fare poorly. Some risk factors have been known for years, based upon careful study of hundreds of patients by the Cooperative Study for Sickle Cell Disease and investigators studying the Jamaican newborn cohort. Other prognostic measures have only recently been defined. Dr. Quinn devotes special attention to stroke and chest syndrome as organ-related complications but also describes attempts to measure overall disease severity and to predict survival. Recently, investigators have attempted to predict factors responsible for early mortality in children and following onset of pulmonary hypertension in adults. In Section III, Dr. Martin Steinberg reviews pharmacologic approaches to sickle cell disease and the rationale for their use. In addition to the inhibition of hemoglobin S polymerization, newer targets have been defined during the past one to two decades. These include the erythrocyte membrane, changes in the red cell intracellular content (especially loss of water), endothelial injury, and free radical production. Hydroxyurea treatment attracted the greatest interest, but many uncertainties remain about its long-term benefits and toxicities. Newer “anti-sickling” agents such as decitabine and short-chain fatty acids also receive attention. Prevention of red cell dehydration, “anti-endothelial” therapy, and marshaling the potentially beneficial effects of nitric oxide are other new and exciting approaches.

scholarly journals Nonsense on Stilts – Part 1: The ICER 2020-2023 Value Assessment Framework for Constructing Imaginary Worlds

2020 ◽  
Vol 11 (1) ◽  
pp. 12 ◽  
Author(s):  
Paul Langley
Keyword(s):  
Health Care ◽  
Care Delivery ◽  
Measurement Theory ◽  
Lifetime Cost ◽  
Health Technology ◽  
Disease Stage ◽  
Value Assessment ◽  
Assessment Framework ◽  
Reference Case ◽  
Utility Scores

Previous commentaries in the Formulary Evaluation section of INNOVATIONS in Pharmacy have pointed to the lack of credibility in modeled claims for cost-effectiveness and associated recommendations for pricing and access by the Institute for Clinical and Economic Review (ICER). The principal objection to ICER reports has been that their modeled claims fail the standards of normal science: they are best seen as pseudoscience. The purpose of this latest commentary is to provide a critique of the recently released ICER 2020 Value Assessment Framework (VAF). Although ICER has taken upon itself the pole position in health technology assessments and recommendations for product pricing in the US health care system, the incremental, lifetime cost-per-QALY modeling methodology should not be taken seriously. The creation of imaginary modeled worlds, built entirely from assumption, fails the demarcation test between science and pseudoscience. The ICER evidence reports are best seen as the health technology assessment equivalent of ‘intelligent design’ in counterpoint to ‘natural selection’. It is surprising, therefore, that health care decision makers should take ICER’s recommendations seriously as providing ‘approximate information’ for formulary decision making. What is not appreciated is that the claims made by ICER lack credibility, are impossible to evaluate and lack the ability to be replicated across treatment settings. Indeed, the models presented under the guise of a ‘state of the art’ value assessment were never intended to support evaluable claims. We have no idea and will never know if they are right or if they are wrong. ICER’s position becomes even more untenable once the models presented are assessed in detail. Without in any way supporting the ICER methodology, it is worth noting that all too often ICER’s claims for incremental QALYs in specific models are based upon what appears to be, from the limited evidence presented, a casual and ad hoc assemblage of utility scores from diverse constructs. This is a critical weakness given the role attributed by ICER to the modeled cost-per-QALY claims as central to ICERs imaginary value assessment. ICER also overlooks the fact that the utility scores it captures from the literature to populate its imaginary reference case world lack objectivity. They are ordinal rather than interval measures. To apply these manifest scores to time spent in a disease stage and then aggregate these over different disease stages is nonsensical. The critical issue is one of instrument development. The case made here is for the application of Rasch Measurement Theory (RMT) to construct a unidimensional instrument with interval properties, in this case from the needs fulfillment construct of quality of life (QoL). Unless an instrument meets RMT standards in its development, the logic of Rasch modeling to achieve fundamental measurement standards means that other scales are, by definition, ordinal. It is absurd to ‘assume’ they are interval. RMT is designed to create instruments to evaluate change and test hypotheses. In the absence of instruments that have RMT properties, the cost-per-QALY reference case modelling meme collapses. It is an analytical dead end. If we are to support a meaningful scientific program to discover new facts to support health care delivery and improve the lives of patients, caregivers and their families, then ICER should be put to one side.   Article Type: Commentary

scholarly journals Epidemiology of hereditary anemias in Saudi Arabia

2021 ◽  
Author(s):  
Shada Murshed Alharbi ◽  
Jawad Hussain Alshaiti ◽  
Jamila Mofareh Ghazwani ◽  
Afia Mofareh Ghazwani ◽  
Nawaf Mohammed Abushelwah ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Dehydrogenase Deficiency ◽  
Epidemiological Studies ◽  
Cell Disease ◽  
The Past ◽  
Prevalence Trends ◽  
High Prevalence ◽  
Glucose 6 Phosphate Dehydrogenase

The prevalence rates of hereditary anemias in Saudi Arabia are remarkably high when compared to other countries. For instance, estimates show that the prevalence of thalassemia constitutes one of the highest rates globally. Furthermore, it has been demonstrated that epidemiology significantly differs between the different regions across the Kingdom. Therefore, many epidemiological investigations were conducted. In this context, it has been demonstrated that the prevalence of thalassemia ranges from 0.4% to 5.9% in the Northern and Eastern regions, respectively. In the present literature review, we have discussed the different findings of epidemiological studies that studied the epidemiology of hereditary anemias in Saudi Arabia. We mainly discussed the epidemiology of glucose-6-phosphate dehydrogenase deficiency (G6PD), sickle cell disease, and thalassemia. Recent evidence indicates that the trends of β-thalassemia are significantly decreasing over the past years. On the other hand, it has been demonstrated that the prevalence trends of sickle cell disease is constant over the past years. G6PD is also highly prevalent in Saudi Arabia. However, recent evidence is lacking in the literature and needs to be updated by future investigations. Consanguineous marriage has been reported to be an important risk factor for the high prevalence of β-thalassemia and sickle cell disease across the Kingdom.

scholarly journals The Imaginary Worlds of Cure Proportion Modeling: Survivorship and Reference Case Pricing of Transformative Therapies

2019 ◽  
Vol 10 (3) ◽  
pp. 17
Author(s):  
Paul Langley
Keyword(s):  
Incremental Cost ◽  
Business Model ◽  
Fair Value ◽  
Normal Science ◽  
Value Assessment ◽  
Assessment Framework ◽  
Short Term ◽  
Reference Case ◽  
Case Methodology ◽  
Article Type

On August 6, 2019 the Institute for Clinical and Economic Review (ICER) released a set of proposed adaptations to its value assessment framework methods where the intervention under review was considered a ‘single or short-term transformative therapy’ (SST). These adaptations are intended to ‘complement and build upon the upcoming update to the overall ICER assessment framework…’.  The purpose of this commentary is to review the proposed cure proportion modeling reference case framework for assessing the value of SSTs together with ICER’s ‘recommendations for fair value-based pricing …’. Following previous commentaries on the ICER value assessment framework, the question raised is whether the proposed cure proportion modeling standards meet those of normal science:  is the modeling proposed capable of generating value claims for the intervention that are credible, evaluable and replicable? The proposed standards for transformative therapies do not change the underlying commitment to reference case modeling. At the same time, the cure proportion modeling proposed adaptations have to be seen in the context of the concerns expressed by ICER that their reference case model can be used to justify substantial one-off SST pricing. This follows from the ICER incremental cost per QALY willingness to pay thresholds where the SST QALY gains are sufficient, at even a $50,000 QALY cut-off, to support SST pricing in the millions of dollars. ICER has two options: (i) abandon the imaginary reference case methodology, which is the ICER core business model and would represent an ironic reversal, or (ii) attempt to bolt-on adaptations, possibly incorporating revised survivorship profiles using cure proportion modeling, that supports a modified imaginary reference case ‘rescue’ model for SSTs designed specifically to generate pricing recommendations that may be considered affordable.   Article Type: Commentary

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