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Group-sequential alpha spending — Examples
1 · Prerequisites
- Absolute and Conditional Convergence; Rearrangement; Products
- Algebraic Closure, Embeddings, and Separability
- Algebraic Extensions, Extension Degree, and Finite Fields
- Areas of Elementary Plane Figures
- Binary Operations, Monoids, Groups and Subgroups
- Central Limit Theorems
- Characteristic Functions Inversion and Continuity
- Compactness
- Compactness in Metric Spaces
- Complete Metrizability, Čech-Completeness, and Baire Category
- Completeness, Completion, and Uniform Continuity
- Complex Lp Spaces and Test-Function Conventions
- Composition Series, the Jordan–Hölder Theorem and Solvable Groups
- Conditional Distributions and Regular Conditional Probability
- Congruences, the Integers Modulo n and the Chinese Remainder Theorem
- Construction of the Natural Numbers
- Construction of the Real Numbers via Cauchy Sequences
- Construction of the Real Numbers via Dedekind Cuts
- Continuity, IVT, EVT, and Uniform Continuity
- Cosets, Index and Lagrange's Theorem
- Countability and Uncountability
- Countability Axioms and Cardinal Functions
- Cyclic Groups and Direct Products
- Density Separability and Convolution in Lᵖ
- Determinants of Matrices over a Commutative Ring
- Diagonalisation and the Minimal Polynomial
- Divisibility, Euclidean Domains, Principal Ideal Domains and Unique Factorisation
- Divisibility, Greatest Common Divisors and Bézout's Identity
- Dual Spaces, Bilinear and Quadratic Forms, and Sylvester's Law of Inertia
- Eigenvalues, Eigenvectors and the Characteristic Polynomial
- Estimators and Randomized Procedures
- Filters and Ultrafilters
- Finite Counting, Factorials and Binomial Coefficients
- Finite Probability and the Probabilistic Method
- Foundations of the Real Numbers for Analysis
- Fourier Transform Convolution and Approximate Identities
- Fubini and Change of Variables
- Fundamental Trigonometric Identities
- Gaussian Elimination, Elementary Matrices and Reduced Row Echelon Form
- Group Actions, Orbits, Stabilisers and Cayley's Theorem
- Group Homomorphisms and the Isomorphism Theorems
- Group-sequential alpha spending
- Hausdorff via the Diagonal
- Ideals, Quotient Rings and the Isomorphism Theorems for Rings
- Improper and Parameter-Dependent Multiple Integrals
- Improper Integrals
- Independence Borel Cantelli and Zero One Laws
- Infinite Product Measures and Kolmogorov Extension
- Inner Product Spaces, Gram-Schmidt, Projections and Adjoints
- Lebesgue Measure on Euclidean Space
- Limits of Real Functions
- limsup, liminf, and Subsequential Limits
- Linear Independence, Bases and Dimension
- Linear Transformations, Rank-Nullity and Quotient Spaces
- Loss, Risk and Decision Theory
- Matrices, the Matrix of a Linear Map, and Change of Basis
- Measurable Functions and Simple Approximation
- Measures and Their Basic Properties
- Metric Spaces
- Mixed Partials, Taylor Formulae, and Extrema
- Modes of Convergence Egorov and Lusin
- Monotone Functions, Discontinuities, and Continuity Sets
- Monotone Sequences, Bolzano-Weierstrass, and Cauchy Completeness
- Normal Subgroups and Quotient Groups
- Order, Zorn's Lemma, and the Axiom of Choice
- Outer Measure and the Caratheodory Extension Theorem
- Partitions of Unity and Paracompactness
- Pointwise Extended-Real Function Products
- Polynomial Rings, the Division Algorithm and Roots
- Power Series and Real-Analytic Functions
- Primes, Euclid's Lemma and the Fundamental Theorem of Arithmetic
- Probability Spaces Random Variables and Expectation
- Product Measures and the Fubini Tonelli Theorems
- Properties of the Integral and the Working FTC
- Radon Measures and the Riesz Markov Kakutani Theorem
- Relations, Functions, and Quotients
- Rings, Subrings, Integral Domains and Fields
- Rⁿ as a Normed Space; Vector-Valued Functions
- Roots, Rational Powers, and Classical Inequalities
- Separation Axioms: the Hierarchy
- Sequences and Limits
- Sequences and Series of Functions; Uniform Convergence
- Series: Convergence and the Nonnegative Tests
- Sigma Algebras and Borel Sets
- Signed and Complex Measures Hahn and Jordan
- Simple Field Extensions and the Construction of the Complex Numbers
- Sine, Cosine, and the Definition of Pi
- Splitting Fields
- Statistical Experiments, Models and Identifiability
- Subspaces, Products, and Quotients
- Suprema and Infima
- Sylow's Theorems, p-Groups and Nilpotent Groups
- Symmetric Groups, Cycle Decomposition and the Sign Homomorphism
- Tests, Neyman–Pearson and Valid P-values
- The Cantor Set, Baire Category, and Measure Zero in ℝ
- The Complex Exponential and Euler's Formula
- The Derivative and the Mean Value Theorems
- The Determinant of a Linear Operator, Cofactors and Cramer's Rule
- The Exponential Function
- The Fundamental Theorem of Algebra
- The Fundamental Theorem of Finite Abelian Groups
- The Galois Correspondence
- The Inverse and Implicit Function Theorems
- The Lebesgue and Riemann Integrals Compared
- The Lebesgue Integral and the Convergence Theorems
- The Logarithm and General Powers
- The Lᵖ Spaces Holder Minkowski and Riesz Fischer
- The Maximal Function and Lebesgue Differentiation
- The Radon Nikodym Theorem and Lebesgue Decomposition
- The Riemann Integral in Rᵐ and Jordan Content
- The Riemann Integral: Definition and Integrability
- The Spectral Theorem, Positive Operators and Singular Value Decomposition
- The Topology of Euclidean Space
- The Total Derivative in ℝᵐ → ℝⁿ
- The ZFC Axioms and the Basic Set Constructions
- Topological Spaces and Continuity
- Topology of ℝ
- Triangularisation, Generalised Eigenspaces and Jordan Canonical Form
- Urysohn's Lemma and the Tietze Extension Theorem
- Vector Spaces, Linear Subspaces, Span and Direct Sums
- Weak Convergence Tightness and Representation
2 · Summary
These worked two-look designs use the Pocock-type and O’Brien–Fleming-type spending curves under the same canonical Gaussian covariance. They calculate the first boundary from its marginal null law and define the final boundary as the unique root of the joint crossing equation. Both examples calibrate their symmetric two-sided absolute-value crossings directly.
3 · Logical flowchart
4 · Definitions, theorems and proofs
None yet.
5 · Examples, counterexamples and false statements
Two-look Pocock-type symmetric spending
Example
Assume AC, take , , , and . Use the symmetric two-sided Pocock-type spending curve where and is the natural logarithm. Its first spend is . Let be the standard normal CDF and let be the unique real number with . The first symmetric boundary is . The second boundary is the unique finite satisfying where the canonical covariance gives . The joint probability of continuing past look 1 and crossing at look 2 is therefore . Conditional on continuing, the second-look crossing probability is . The Pocock-type spending curve does not assert constant standardized boundaries; each boundary is calibrated under the joint law.
Facts & Assumptions
Given: AC, the two planned information fractions , , the canonical Gaussian null law, and the stated Pocock-type spending curve. Verify the curve is admissible and identify the two two-sided boundaries exactly.
Canonical group-sequential alpha-spending design: A design has nondecreasing with , , and canonical covariance for .
Recursive group-sequential boundary calibration: At a positive increment the symmetric two-sided boundary solves .
Group-sequential boundaries exist uniquely and spend alpha exactly: Every positive increment has a unique finite boundary and at each look.
Standard normal and normal laws: The standard normal law has density .
The standard normal density has total mass one: The density is positive and has integral one.
The real exponential function and the number by a power series: The real exponential is defined by its power series and .
The natural logarithm as the inverse of the exponential function: For , is the unique real with .
Order, continuity, range, and the product, quotient, and reciprocal laws for the natural logarithm: is continuous and strictly increasing on , and .
The exponential function is strictly increasing: The real exponential is strictly increasing on .
Continuity from below for measures: The measure of the union of an increasing sequence of measurable sets is the supremum of their measures.
Intermediate value theorem, by bisection with a canonical left-half rule: a continuous function on takes every value between and : A continuous real function on a closed bounded interval attains every value between its endpoint values.
The Axiom of Choice: Assume the Axiom of Choice.
Verification
Since by its power series and is strictly increasing by [F9], . Thus increases from to as goes from to . By [F7]–[F8], , , and is nondecreasing with values in . At this gives and .
The standard normal CDF satisfies for . By [F4]–[F5], this difference is positive and at most , so is strictly increasing and continuous. Its limits at and are and : [F10] applied to gives the lower-tail limit, and [F10] applied to gives the upper-tail limit; the density has no point masses. Therefore [F11] gives a unique for every . In particular is finite, positive, and symmetry and atomlessness give .
The canonical covariance matrix is , so its determinant is and the correlation is . Applying [F2]–[F3] at the second look gives the unique finite satisfying the displayed cumulative two-sided crossing equation. The event and the continued-path event are disjoint and their union is the final rejection event. Hence the continued-path event has joint probability , and since , its conditional probability given continuation is . The total rejection probability is .
Two-look O’Brien–Fleming-type spending
Example
Assume AC, take , , , and . Let be the standard normal CDF, and write for the unique real number with . Use the two-sided O’Brien–Fleming-type spending curve Its first spend is . The first symmetric two-sided boundary is . The second boundary is the unique finite satisfying where . The two-sided boundaries come from this absolute-value crossing equation, not from doubling the one-sided boundaries.
Facts & Assumptions
Given: AC, , , , the canonical Gaussian null law, and the displayed O’Brien–Fleming-type spending curve. Verify the spending conditions and identify the two symmetric boundaries.
Canonical group-sequential alpha-spending design: An admissible spending function is nondecreasing from into , with endpoint values and ; the symmetric two-sided crossing event at look is .
Recursive group-sequential boundary calibration: At a positive increment the symmetric two-sided boundary solves .
Group-sequential boundaries exist uniquely and spend alpha exactly: Every positive spending increment has a unique finite boundary and at each look.
Standard normal and normal laws: The standard normal law is the probability measure with density .
The standard normal density has total mass one: The density is positive and has integral one.
Continuity from below for measures: For an increasing sequence of measurable sets, the measure of their union is the supremum of their measures.
Intermediate value theorem, by bisection with a canonical left-half rule: a continuous function on takes every value between and : A continuous real function on a closed bounded interval takes every value between its endpoint values.
The Axiom of Choice: Assume the Axiom of Choice.
Verification
Define . For , positivity in [F5] gives , while gives . Thus is strictly increasing and continuous.
The density is even, so . Applying [F6] to the increasing upper half-lines gives as ; applying it to the increasing lower half-lines gives as . Hence [F7] gives a unique quantile for each , and .
For , decreases as increases; since increases, is nondecreasing. Its values are positive and at most , and its limit at is by the upper-tail limit in step 2.1. Thus the declared makes it admissible. At , its value is , with .
By symmetry of the density in [F4], for . Therefore has first-look crossing probability . The canonical covariance matrix is , so its determinant is and the correlation is . Applying [F2]–[F3] at the second look gives the unique finite satisfying the displayed cumulative two-sided crossing equation, with total probability .
Sources
- David L. DeMets and K. K. Gordon Lan, Interim Analysis: The Alpha Spending Function Approach, Statistics in Medicine 13 (1994), PDF pp. 6–7
- Michael J. Grayling, James M. S. Wason, and Adrian P. Mander, Group Sequential Clinical Trial Designs for Normally Distributed Outcome Variables, The Stata Journal 18(2) (2018), PDF pp. 2–4
- Giorgos Minas, Multivariate Global Testing and Adaptive Designs, PhD thesis, Chapter 5 §§5.3–5.3.1, printed pp. 72–73