Assessment-schedule matching in unanchored indirect treatment comparisons of progression-free survival in cancer studies

Background The timing of efficacy-related clinical events recorded at scheduled study visits in clinical trials are interval censored, with the interval duration pre-determined by the study protocol. Events may happen any time during that interval but can only be detected during a planned or unplanned visit. Disease progression in oncology is a notable example where the time to an event is affected by the schedule of visits within a study. This can become a source of bias when studies with varying assessment schedules are used in unanchored comparisons using methods such as matching-adjusted indirect comparisons. Objective We illustrate assessment-time bias (ATB) in a simulation study based on data from a recent study in second-line treatment for locally advanced or metastatic urothelial carcinoma, and present a method to adjust for differences in assessment schedule when comparing progression-free survival (PFS) against a competing treatment. Methods A multi-state model for death and progression was used to generate simulated death and progression times, from which PFS times were derived. PFS data were also generated for a hypothetical comparator treatment by applying a constant hazard ratio (HR) to the baseline treatment. Simulated PFS times for the two treatments were then aligned to different assessment schedules so that progression events were only observed at set visit times, and the data were analysed to assess the bias and standard error of estimates of HRs between two treatments with and without assessment-schedule matching (ASM). Results ATB is highly affected by the rate of the event at the first assessment time; in our examples, the bias ranged from 3 to 11% as the event rate increased. The proposed method relies on individual-level data from a study and attempts to adjust the timing of progression events to the comparator’s schedule by shifting them forward or backward without altering the patients’ actual follow-up time. The method removed the bias almost completely in all scenarios without affecting the precision of estimates of comparative effectiveness. Conclusions Considering the increasing use of unanchored comparative analyses for novel cancer treatments based on single-arm studies, the proposed method offers a relatively simple means of improving the accuracy of relative benefits of treatments on progression times

The open future, bivalence and assertion

It is highly intuitive that the future is open and the past is closed—whereas it is unsettled whether there will be a fourth world war, it is settled that there was a first. Recently, it has become increasingly popular to claim that the intuitive openness of the future implies that contingent statements about the future, such as ‘there will be a sea battle tomorrow,’ are non-bivalent (neither true nor false). In this paper, we argue that the non-bivalence of future contingents is at odds with our pre-theoretic intuitions about the openness of the future. These are revealed by our pragmatic judgments concerning the correctness and incorrectness of assertions of future contingents. We argue that the pragmatic data together with a plausible account of assertion shows that in many cases we take future contingents to be true (or to be false), though we take the future to be open in relevant respects. It follows that appeals to intuition to support the non-bivalence of future contingents is untenable. Intuition favours bivalence

Limits of Abductivism About Logic

I argue against abductivism about logic, which is the view that rational theory choice in logic happens by abduction. Abduction cannot serve as a neutral arbiter in many foundational disputes in logic because, in order to use abduction, one must first identify the relevant data. Which data one deems relevant depends on what I call one's conception of logic. One's conception of logic is, however, not independent of one's views regarding many of the foundational disputes that one may hope to solve by abduction

A Practical Theory of Language-integrated Query

Language-integrated query is receiving renewed attention, in part because of its support through Microsoft’s LINQ framework. We present a practical theory of language-integrated query based on quotation and normalisation of quoted terms. Our technique supports join queries, abstraction over values and predicates, composition of queries, dynamic generation of queries, and queries with nested intermediate data. Higher-order features prove useful even for constructing first-order queries. We prove a theorem characterising when a host query is guaranteed to generate a single SQL query. We present experimental results confirming our technique works, even in situations where Microsoft’s LINQ framework either fails to produce an SQL query or, in one case, produces an avalanche of SQL queries

Extensional Rewriting with Sums

Abstract. Inspired by recent work on normalisation by evaluation for sums, we propose a normalising and confluent extensional rewriting theory for the simply-typed λ-calculus extended with sum types. As a corollary of confluence we obtain decidability for the extensional equational theory of simply-typed λ-calculus extended with sum types. Unlike previous decidability results, which rely on advanced rewriting techniques or advanced category theory, we only use standard techniques.

Towards a canonical classical natural deduction system

This paper studies a new classical natural deduction system, presented as a typed calculus named \lml. It is designed to be isomorphic to Curien-Herbelin's calculus, both at the level of proofs and reduction, and the isomorphism is based on the correct correspondence between cut (resp. left-introduction) in sequent calculus, and substitution (resp. elimination) in natural deduction. It is a combination of Parigot's $\lambda\mu$-calculus with the idea of ``coercion calculus'' due to Cervesato-Pfenning, accommodating let-expressions in a surprising way: they expand Parigot's syntactic class of named terms. This calculus aims to be the simultaneous answer to three problems. The first problem is the lack of a canonical natural deduction system for classical logic. \lml is not yet another classical calculus, but rather a canonical reflection in natural deduction of the impeccable treatment of classical logic by sequent calculus. The second problem is the lack of a formalization of the usual semantics of Curien-Herbelin's calculus, that explains co-terms and cuts as, respectively, contexts and hole-filling instructions. The mentioned isomorphism is the required formalization, based on the precise notions of context and hole-expression offered by \lml. The third problem is the lack of a robust process of ``read-back'' into natural deduction syntax of calculi in the sequent calculus format, that affects mainly the recent proof-theoretic efforts of derivation of $\lambda$-calculi for call-by-value. An isomorphic counterpart to the $Q$-subsystem of Curien-Herbelin's-calculus is derived, obtaining a new $\lambda$-calculus for call-by-value, combining control and let-expressions.Fundação para a Ciência e a Tecnologia (FCT

Everything old is new again: Quoted Domain Specific Languages

We describe a new approach to domain specific languages (DSLs), called Quoted DSLs (QDSLs), that resurrects two old ideas: quotation, from McCarthy's Lisp of 1960, and the subformula property, from Gentzen's natural deduction of 1935. Quoted terms allow the DSL to share the syntax and type system of the host language. Normalising quoted terms ensures the subformula property, which guarantees that one can use higher-order types in the source while guaranteeing first-order types in the target, and enables using types to guide fusion. We test our ideas by re-implementing Feldspar, which was originally implemented as an Embedded DSL (EDSL), as a QDSL; and we compare the QDSL and EDSL variants

Natural deduction and arbitrary objects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43180/1/10992_2004_Article_BF00542649.pd