scholarly journals Value Assessment, Real World Evidence and Fundamental Measurement: Version 3.0 of the Minnesota Formulary Submission Guidelines

2020 ◽  
Vol 11 (4) ◽  
pp. 12
Author(s):  
Paul C. Langley
Keyword(s):  
Evidence Base ◽  
Pharmaceutical Products ◽  
Normal Science ◽  
Value Assessment ◽  
New Paradigm ◽  
Therapeutic Class ◽  
New Information ◽  
Real World Evidence ◽  
Fatal Flaw ◽  
New Evidence

This latest version of the Minnesota guidelines is intended to reassert the application of the standards of normal science in formulary submissions for new and existing pharmaceutical products and devices. This represents a paradigm shift from the existing value assessment standards which are focused on imaginary or I-QALY modeling of lifetime claims. The proposed new paradigm rejects this as pseudoscience; a failure to recognize the standards of normal science, in particular a failure to recognize the constraints of fundamental measurement. As a result, current health technology assessment is dominated by value assessments that create claims that are neither credible, nor empirically evaluable or replicable. The fatal flaw is the failure to recognize that QALYS are an impossible mathematical construct (hence the term I-QALY). The proposed paradigm recognizes that if there are claims for product value then, regardless of whether the claim is for clinical impact, quality of life or resource utilization, all claims must be empirically evaluable. If not, then they should be rejected. The Minnesota guidelines propose a new evidence based approach to formulary assessment, together with ongoing disease area and therapeutic class reviews. The focus is on claims that are specific to target patient populations that are claims for specific attributes and are consistent with the axioms of fundamental measurement. Manufacturers are asked to support claims assessment through protocols detailing the evidence base for claims assessment, the timelines for those assessments and the process by which claims assessments are reported back to formulary committees. Value assessment leads naturally to value contracting, revisiting provisional prices as new information is discovered and delivered to the formulary committee.    

scholarly journals Post QALY: Scientific Approaches to Real World Formulary Decision Making

2020 ◽  
Vol 11 (2) ◽  
pp. 19
Author(s):  
Paul Langley ◽  
Stephen McKenna
Keyword(s):  
Decision Making ◽  
Medical Devices ◽  
Evidence Base ◽  
Pharmaceutical Products ◽  
Normal Science ◽  
Value Assessment ◽  
Scientific Methods ◽  
Article Type ◽  
The Us ◽  
The Uk

The purpose of this anniversary supplement for Innovations in Pharmacy is to consider and / or propose modern, scientific methods for determining the evidence base for the fair pricing and accessibility of pharmaceutical products and medical devices. At present, such decisions are based on the construction of imaginary value assessment models that fail to meet the standards of normal science. Such a business model has been adopted by the Institute for Clinical and Economic Review (ICER) in the US, NICE in the UK and in a number of other countries.   Article Type: Call for Papers

scholarly journals To Dream the Impossible Dream: The Commitment by the Institute for Clinical and Economic Review to Rewrite the Axioms of Fundamental Measurement for Hemophilia A and Bladder Cancer Value Claims

2020 ◽  
Vol 11 (4) ◽  
pp. 22
Author(s):  
Paul Langley
Keyword(s):  
Lifetime Cost ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Pharmaceutical Products ◽  
Normal Science ◽  
Value Assessment ◽  
New Paradigm ◽  
Dead End ◽  
Patient Reported ◽  
New Vision

Understandably, after 30 years of ignoring the axioms of fundamental measurement, advocates of creating approximate information through the construction of lifetime cost-per-QALY worlds are somewhat unnerved by the realization that their methodology is incompatible with those axioms. This is made all the more unnerving when it is pointed out that this incompatibility was pointed out over 30 years ago, following the formalization of those axioms almost 80 years ago. Why this was overlooked is a mystery. The result was a commitment to the application of ordinal utility and other patient reported outcome measures to support claims for response to competing therapies; most egregiously, the advocacy of cost-per-QALY lifetime models and willingness to pay thresholds to support recommendations for pricing and access to pharmaceutical products and devices. Although this incompatibility has been pointed out in respect of simulation modeling, to groups such as the Institute for Clinical and Economic Review (ICER) they press on, producing evidence reports and recommendations for emerging products that fail the standards of normal science.  While these are an analytical dead end, ICER has nowhere else to go. This is their business model; to admit otherwise would mean withdrawing their many evidence reports and admit they were wrong. ICER has rejected this; rather it has decided, together with its academic consultants, to challenge the axioms of fundamental measurement, to produce a parallel measurement universe that can sustain QALYs and the imaginary simulation lifetime models. The purpose here is to make clear that ICER is manifestly wrong and that there is no way it can maintain its credibility in pursuing this path. This is achieved by a deconstruction of the arguments put forward by ICER to defend its new vision of the axioms of fundamental measurement, a vision which provides a case study in the distinction between justified belief and opinion.  Fortunately, we have the framework for a new paradigm in value assessment; a paradigm that recognizes the standards of normal science and rejects belief in an alternative reality consistent with fundamental measurement axioms.

scholarly journals Medicaid Formulary Decisions and the Institute for Clinical and Economic Review: Abandoning Pseudoscience in Imaginary Pharmaceutical Pricing Claims

2021 ◽  
Vol 12 (1) ◽  
pp. 11
Author(s):  
Paul Langley
Keyword(s):  
Simulation Models ◽  
Standard Of Care ◽  
Evidence Base ◽  
Quality Adjusted Life Year ◽  
Unintended Consequences ◽  
Normal Science ◽  
Pharmaceutical Pricing ◽  
Real World Evidence ◽  
Health Decision ◽  
The One

Medicaid formulary committees and other gatekeepers face a difficult task. On the one hand they can utilize technical expertise in evaluating the real world evidence for clinical, quality of life and resource utilization claims for competing products while on the other hand they may be asked to assess claims built by simulation models for pricing and product access. A common option has been to take modeled claims from third parties such as the Institute for Clinical and Economic Review (ICER) at face value without challenging the model structure, its assumptions and its incremental cost-per-QALY claims set against competing products or the existing standard of care. Unfortunately, from the available evidence, it seems clear that many formulary assessment groups, last but not least those for whom the ICER modeling claims are targeted, have little if any appreciation of the limitations of ICER modeling. There are two substantive issues: (i) a failure to appreciate the limitations imposed by the standards of normal science for credible, empirically evaluable and replicable product claims and (ii) an understanding of limitations imposed by the axioms of fundamental measurement. In the latter case, a failure to recognize that the quality adjusted life year (QALY) is an impossible mathematical construct (hence the I-QALY). To these limitations should be added the potential for constructing competing imaginary claims. Surprisingly, ICER has provided the ideal opportunity to construct competing claims with the launch in late 2020 of the ICER Analytics cloud platform. Formulary committees and other health decision makers should be aware that claims based on the ICER Analytics platform together with competing lifetime modelled claims all fail the standards of normal science. Factoring these into formulary decisions is not only misguided but may have unintended consequences for pricing and access that may disadvantage significantly patients and caregivers. We have spent too much time debating the merits or otherwise of the I-QALY for targeted patient groups with the parties failing to recognize that the focus on simulated cost-per-I-QALY value assessments is a mathematical folly; I-QALY claims are a chimera. The I-QALY, at long last, should be abandoned together with modelled lifetime simulations. Medicaid formulary decision makes should rethink the required evidence base for formulary decisions and negotiations. Care should be taken to revisit previous negotiations where ICER recommendations have been utilized to support pricing and access.

scholarly journals Lopinavir and Nelfinavir Induce the Accumulation of Crystalloid Lipid Inclusions within the Reservosomes of Trypanosoma cruzi and Inhibit Both Aspartyl-Type Peptidase and Cruzipain Activities Detected in These Crucial Organelles

2021 ◽  
Vol 6 (3) ◽  
pp. 120
Author(s):  
Leandro S. Sangenito ◽  
Miria G. Pereira ◽  
Thais Souto-Padron ◽  
Marta H. Branquinha ◽  
André L. S. Santos
Keyword(s):  
Trypanosoma Cruzi ◽  
Opportunistic Infections ◽  
Lipid Inclusion ◽  
Transmission Electron ◽  
New Information ◽  
Lipid Inclusions ◽  
Immunodeficiency Virus ◽  
Parasite Viability ◽  
Aspartyl Peptidases ◽  
New Evidence

Several research groups have explored the repositioning of human immunodeficiency virus aspartyl peptidase inhibitors (HIV-PIs) on opportunistic infections caused by bacteria, fungi and protozoa. In Trypanosoma cruzi, HIV-PIs have a high impact on parasite viability, and one of the main alterations promoted by this treatment is the imbalance in the parasite’s lipid metabolism. However, the reasons behind this phenomenon are unknown. In the present work, we observed by transmission electron microscopy (TEM) that the treatment of T. cruzi epimastigotes with the HIV-PIs lopinavir and nelfinavir induced a huge accumulation of crystalloid-shaped lipids within the reservosomes, most of them deforming these key organelles. As previously reported, those structures are characteristic of lipid inclusions formed mostly of cholesterol and cholesterol-esters. The fractionation of nontreated epimastigotes generated two distinct fractions enriched in reservosomes: one mostly composed of lipid inclusion-containing reservosomes (Fraction B1) and one where lipid inclusions were much less abundant (Fraction B2). Interestingly, the extract of Fraction B2 presented enzymatic activity related to aspartyl-type peptidases 3.5 times higher than that found in the extract obtained from Fraction B1. The cleavage of cathepsin D substrate by this class of peptidases was strongly impaired by pepstatin A, a prototypical aspartyl PI, and the HIV-PIs lopinavir and nelfinavir. In addition, both HIV-PIs also inhibited (to a lesser extent) the cruzipain activity present in reservosomes. Finally, our work provides new evidence concerning the presence and supposed participation of aspartyl peptidases in T. cruzi, even as it adds new information about the mechanisms behind the alterations promoted by lopinavir and nelfinavir in the protozoan.

scholarly journals Batalia „szklanej rury”. Współzawodnictwo „starego” i „nowego” w debacie wokół doświadczeń z próżnią z 1647 roku

1970 ◽  
pp. 167-190
Author(s):  
Anna Kołos
Keyword(s):  
Seventeenth Century ◽  
History Of Science ◽  
Scientific Discourse ◽  
Blaise Pascal ◽  
Normal Science ◽  
New Paradigm ◽  
Republic Of Letters ◽  
Knowledge Formation ◽  
History Of ◽  
The Republic

The article addresses the issue of one of the more intense and captivating European scientific disputes, likewise common to Poland, in the era of the seventeenth-century transformation of knowledge formation, which centered around the possibility of the existence of vacuum, and which culminated in 1647. The fundamental aim of the article comes down to an attempt to determine a position in the scientific-cognitive debate, from which the pro and anti-Polish and European representatives of The Republic of Letters (Respublica literaria)  could voice their opinions. In the course of the analysis of the mid-seventeenth century scientific discourse, the reflections of Valeriano Magni, Torricelli, Jan Brożek, Wojciech Wijuk Kojałowicz, Blaise Pascal, Giovanni Elefantuzzi, Jacob Pierius, and Pierre Guiffart are subjected to close scrutiny. From the perspective of contextualism in the history of science, experiments demonstrating the existence of vacuum are perceived as anomalies that fall into the crisis of normal science, largely based on Aristotle’s physics. The conflict between the old and the new is not, however, presented as a battle of progression with epigonism, but merely as a contest between opposing individual views and the concept of science, which before the formation of the new paradigm was accompanied by ambiguous verification criteria.

scholarly journals Frailty, the determinants of health and the new evidence base

2018 ◽  
Vol 1 (1) ◽  
pp. 5-6
Author(s):  
Roman Romero-Ortuno ◽  
Duncan R. Forsyth
Keyword(s):  
Evidence Base ◽  
Determinants Of Health ◽  
New Evidence

Newton's financial misadventures in the South Sea Bubble

2018 ◽  
Vol 73 (1) ◽  
pp. 29-59 ◽  
Author(s):  
Andrew Odlyzko
Keyword(s):  
The South ◽  
Research Directions ◽  
John Maynard Keynes ◽  
Isaac Newton ◽  
Market Rationality ◽  
New Information ◽  
Hard Evidence ◽  
South Sea ◽  
New Research ◽  
New Evidence

A very popular investment anecdote relates how Isaac Newton, after cashing in large early gains, staked his fortune on the success of the South Sea Company of 1720 and lost heavily in the ensuing crash. However, this tale is based on only a few items of hard evidence, some of which are consistently misquoted and misinterpreted. A superficially plausible contrarian argument has also been made that he did not lose much in that period, and John Maynard Keynes even claimed Newton successfully surmounted the South Sea Bubble. This paper presents extensive new evidence that while Newton was a successful investor before this event, the folk tale about his making large gains but then being drawn back into that mania and suffering large losses is almost certainly correct. It probably even understates the extent of his financial miscalculations. Incidental to the clarification of this prominent issue, a controversy between Dale et al . and Shea about an aspect of market rationality during that bubble is settled. Some new information is also presented about Thomas Guy, famous for making a fortune out of the Bubble that paid for the establishment of Guy's Hospital, and other investors. The work reported here suggests new research directions and perspectives on bubbles.

Evaluating Credence Change

2019 ◽  
pp. 127-151
Author(s):  
Julia Staffel
Keyword(s):  
New Information ◽  
New Evidence

Chapter 7 shows how the rationality measures we established in previous chapters can be used to evaluate changes in a thinker’s credences. The focus is on how we can evaluate credence changes in thinkers who reason from irrational starting points. I consider three types of changes: cases in which the thinker revises their credences (i) without learning new information or adding new attitudes; (ii) without learning new information, but adding new attitudes; (iii) as a response to learning new evidence. Examining those cases leads to some interesting discoveries: An incoherent thinker can always form new credences based on their existing incoherent credences without becoming more incoherent. Also, the identification of good patterns of reasoning is of very limited benefit in dealing with irrational thinkers.

scholarly journals Belle Fourche River-Cheyenne River Drainage Divide Area in the Wyoming Powder River Basin Analyzed by Topographic Map Interpretation Methods, USA

2018 ◽  
Vol 10 (2) ◽  
pp. 1
Author(s):  
Eric Clausen
Keyword(s):  
River Basin ◽  
Powder River Basin ◽  
Normal Science ◽  
Topographic Map ◽  
New Paradigm ◽  
River Drainage ◽  
The North ◽  
Map Interpretation ◽  
New Research ◽  
Cheyenne River

The dearth of scientific literature in which specific erosional landform origins are determined is an example of what Thomas Kuhn considered a scientific crisis. Scientific crises arise when scientists following their discipline’s established paradigm’s rules, or doing what Kuhn calls normal science, cannot explain observed evidence. Scientific crises are resolved in one of three ways. Normal science may eventually explain the evidence and normal science returns, the unsolved problems may be identified and labeled and left for future scientists to solve, or a new paradigm may emerge with an ensuing battle over its acceptance. To succeed any new paradigm must demonstrate its ability to explain the previously unexplained evidence and also open up new research opportunities. During the 20th century’s first half regional geomorphologists abiding by their discipline’s paradigm rules unsuccessfully tried to explain origins of numerous erosional landforms, such as drainage divides and erosional escarpments. Their failures eventually caused the regional geomorphology discipline, at least that part of the discipline concerned with determining specific erosional landform origins, to almost completely disappear. A new and fundamentally different geomorphology paradigm that requires massive southeast-oriented continental ice sheet melt-water floods to have flowed across the Powder River Basin has the ability to explain specific erosional landform origins and is demonstrated here by using detailed topographic map evidence to show how large southeast-oriented floods eroded the Powder River Basin’s Belle Fourche River-Cheyenne River drainage divide segment, eroded through valleys now crossing that drainage divide segment, eroded the Powder River Basin’s Belle Fourche River valley, established Belle Fourche and Cheyenne River Powder River Basin tributary valley orientations, and eroded the north-facing Pine Ridge Escarpment. The success of this and other similar new paradigm demonstrations suggest many if not all specific erosional landform origins can be determined.

Reconstructing European insolvency law – putting in place a new paradigm

Legal Studies ◽  
2010 ◽  
Vol 30 (1) ◽  
pp. 126-146 ◽  
Author(s):  
Gerard McCormack
Keyword(s):  
Forum Shopping ◽  
New Paradigm ◽  
Insolvency Law ◽  
Race To The Bottom ◽  
American Experience ◽  
European Insolvency Regulation ◽  
Insolvency Regulation ◽  
Fatal Flaw

This paper critically examines the European Insolvency Regulation. It suggests the Regulation contains a fatal flaw at its heart; namely the ‘centre of main interests’ or COMI test governing the exercise of universal insolvency jurisdiction. The paper argues for greater jurisdictional flexibility to replace the COMI test and defends this proposal against charges that it will contribute to an excess of ‘forum shopping’ and encourage a ‘race to the bottom’. The American experience with bankruptcy court competition is considered in this connection.

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