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Group-sequential alpha spending — Examples

1 · Prerequisites

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

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Two-look Pocock-type symmetric spending

Example

Assume AC, take K=2, t1=1/2, t2=1, and α=1/20. Use the symmetric two-sided Pocock-type spending curve AP(0)=0,AP(t)=αlog⁡(1+(e−1)t)(0<t≤1), where e=exp⁡(1) and log⁡ is the natural logarithm. Its first spend is a1=αlog⁡((1+e)/2). Let Φ(x)=P0(Z1≤x) be the standard normal CDF and let q(u) be the unique real number with Φ(q(u))=u. The first symmetric boundary is c1=q(1−a1/2). The second boundary is the unique finite c2 satisfying P0(∣Z1∣≥c1 or ∣Z2∣≥c2)=α, where the canonical covariance gives Corr⁡0(Z1,Z2)=1/2. The joint probability of continuing past look 1 and crossing at look 2 is therefore α−a1. Conditional on continuing, the second-look crossing probability is (α−a1)/(1−a1). 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 t1=1/2,t2=1, α=1/20, 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.

[F1]

Canonical group-sequential alpha-spending design: A design has nondecreasing A:[0,1]→[0,α] with A(0)=0, A(1)=α, and canonical covariance Σjk=tj/tk for j≤k.

[F2]

Recursive group-sequential boundary calibration: At a positive increment the symmetric two-sided boundary solves P0(Rk−1∪{∣Zk∣≥ck})=A(tk).

[F3]

Group-sequential boundaries exist uniquely and spend alpha exactly: Every positive increment has a unique finite boundary and P0(Rk)=A(tk) at each look.

[F4]

Standard normal and normal laws: The standard normal law has density ϕ(x)=e−x2/2/2π.

[F5]

The standard normal density has total mass one: The density ϕ is positive and has integral one.

[F6]

The real exponential function and the number e by a power series: The real exponential is defined by its power series and e:=exp⁡(1).

[F7]

The natural logarithm as the inverse of the exponential function: For x>0, log⁡x is the unique real y with exp⁡(y)=x.

[F8]

Order, continuity, range, and the product, quotient, and reciprocal laws for the natural logarithm: log⁡ is continuous and strictly increasing on (0,∞), and log⁡1=0.

[F9]

The exponential function is strictly increasing: The real exponential is strictly increasing on R.

[F10]

Continuity from below for measures: The measure of the union of an increasing sequence of measurable sets is the supremum of their measures.

[F11]

Intermediate value theorem, by bisection with a canonical left-half rule: a continuous function on [a,b] takes every value between f(a) and f(b): A continuous real function on a closed bounded interval attains every value between its endpoint values.

[A1]

The Axiom of Choice: Assume the Axiom of Choice.

Verification

1.1givenF1F6F7F8F9algebra

Since exp⁡(0)=1 by its power series and exp⁡ is strictly increasing by [F9], e=exp⁡(1)>1. Thus 1+(e−1)t increases from 1 to e as t goes from 0 to 1. By [F7]–[F8], AP(0)=0, AP(1)=αlog⁡e=α, and AP is nondecreasing with values in [0,α]. At t1=1/2 this gives a1=αlog⁡((1+e)/2) and 0<a1<α.

1.2F4F5F10F11A1algebra

The standard normal CDF satisfies Φ(y)−Φ(x)=∫xyϕ(s) ds for x<y. By [F4]–[F5], this difference is positive and at most (y−x)/2π, so Φ is strictly increasing and continuous. Its limits at −∞ and +∞ are 0 and 1: [F10] applied to (−n,∞) gives the lower-tail limit, and [F10] applied to (−∞,n] gives the upper-tail limit; the density has no point masses. Therefore [F11] gives a unique q(u) for every u∈(0,1). In particular c1=q(1−a1/2) is finite, positive, and symmetry and atomlessness give P0(∣Z1∣≥c1)=a1.

2.1givenF1F2F3step 1.1step 1.2algebra∎

The canonical covariance matrix is Σ=(11/21/21), so its determinant is 1/2>0 and the correlation is 1/2. Applying [F2]–[F3] at the second look gives the unique finite c2 satisfying the displayed cumulative two-sided crossing equation. The event {∣Z1∣≥c1} and the continued-path event {∣Z1∣<c1, ∣Z2∣≥c2} are disjoint and their union is the final rejection event. Hence the continued-path event has joint probability α−a1, and since P0(∣Z1∣<c1)=1−a1>0, its conditional probability given continuation is (α−a1)/(1−a1). The total rejection probability is AP(1)=α.

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Two-look O’Brien–Fleming-type spending

Example

Assume AC, take K=2, t1=1/2, t2=1, and α=0.05. Let Φ(x)=P0(Z1≤x) be the standard normal CDF, and write zp for the unique real number with Φ(zp)=p. Use the two-sided O’Brien–Fleming-type spending curve AOF(0)=0,AOF(t)=2[1−Φ(z0.975t)](0<t≤1). Its first spend is a1=2[1−Φ(z0.9752)]. The first symmetric two-sided boundary is c1=z1−a1/2. The second boundary is the unique finite c2≥0 satisfying P0(∣Z1∣≥c1 or ∣Z2∣≥c2)=0.05, where Corr⁡0(Z1,Z2)=1/2. The two-sided boundaries come from this absolute-value crossing equation, not from doubling the one-sided boundaries.

Facts & Assumptions

Given: AC, K=2, t1=1/2,t2=1, α=0.05, the canonical Gaussian null law, and the displayed O’Brien–Fleming-type spending curve. Verify the spending conditions and identify the two symmetric boundaries.

[F1]

Canonical group-sequential alpha-spending design: An admissible spending function is nondecreasing from [0,1] into [0,α], with endpoint values 0 and α; the symmetric two-sided crossing event at look j is {∣Zj∣≥cj}.

[F2]

Recursive group-sequential boundary calibration: At a positive increment the symmetric two-sided boundary solves P0(Rk−1∪{∣Zk∣≥ck})=A(tk).

[F3]

Group-sequential boundaries exist uniquely and spend alpha exactly: Every positive spending increment has a unique finite boundary and P0(Rk)=A(tk) at each look.

[F4]

Standard normal and normal laws: The standard normal law is the probability measure with density ϕ(x)=e−x2/2/2π.

[F5]

The standard normal density has total mass one: The density ϕ is positive and has integral one.

[F6]

Continuity from below for measures: For an increasing sequence of measurable sets, the measure of their union is the supremum of their measures.

[F7]
[A1]

The Axiom of Choice: Assume the Axiom of Choice.

Verification

1.1F4F5A1algebra

Define Φ(x)=∫−∞xϕ(s) ds. For x<y, positivity in [F5] gives Φ(y)−Φ(x)>0, while ϕ(s)≤1/2π gives Φ(y)−Φ(x)≤(y−x)/2π. Thus Φ is strictly increasing and continuous.

2.1F4F5F6F7step 1.1algebra

The density ϕ is even, so Φ(0)=1/2. Applying [F6] to the increasing upper half-lines (−n,∞) gives Φ(x)→0 as x→−∞; applying it to the increasing lower half-lines (−∞,n] gives Φ(x)→1 as x→+∞. Hence [F7] gives a unique quantile zp for each p∈(0,1), and z0.975>0.

3.1givenF1step 1.1step 2.1algebra

For 0<t≤1, z0.975/t decreases as t increases; since Φ increases, AOF(t) is nondecreasing. Its values are positive and at most 2[1−Φ(z0.975)]=0.05, and its limit at 0 is 0 by the upper-tail limit in step 2.1. Thus the declared AOF(0)=0 makes it admissible. At t1=1/2, its value is a1=2[1−Φ(z0.9752)], with 0<a1<0.05.

4.1givenF1F2F3F4step 2.1step 3.1algebra∎

By symmetry of the density in [F4], P0(∣Z1∣≥c)=2[1−Φ(c)] for c≥0. Therefore c1=z1−a1/2 has first-look crossing probability a1. The canonical covariance matrix is Σ=(11/21/21), so its determinant is 1/2>0 and the correlation is 1/2. Applying [F2]–[F3] at the second look gives the unique finite c2 satisfying the displayed cumulative two-sided crossing equation, with total probability AOF(1)=0.05.

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