The SEQDESIGN Procedure

Example 110.10 Creating Two-Sided Error Spending Designs with and without Overlapping Lower and Upper bold-italic beta Boundaries

(View the complete code for this example.)

This example requests two three-stage group sequential designs for normally distributed statistics. Each design uses a power family error spending function with a specified two-sided alternative hypothesis upper H 1 colon theta 1 equals plus-or-minus 0.2 and early stopping only to accept the null hypothesis upper H 0.

The first design uses the BETAOVERLAP=NOADJUST option to derive acceptance boundary values without adjusting for the possible overlapping of the lower and upper beta boundaries computed from the two corresponding one-sided tests. The second design uses the BETAOVERLAP=ADJUST option to test the overlapping of the beta boundaries at each interim stage based on the two corresponding one-sided tests and then to set the beta boundary values at the stage to missing if overlapping occurs at that stage.

The following statements request a two-sided design with the BETAOVERLAP=NOADJUST option:

ods graphics on;
proc seqdesign altref=0.2 errspend;
   design nstages=3
          method=errfuncpow
          alt=twosided  stop=accept
          betaoverlap=noadjust
          beta=0.09
          ;
run;

The "Design Information" table in Output 110.10.1 displays design specifications and the derived statistics for the first design. With the specified alternative reference theta 1 equals 0.2, the maximum information is derived.

Output 110.10.1: Design Information

The SEQDESIGN Procedure
Design: Design_1

Design Information
Statistic Distribution Normal
Boundary Scale Standardized Z
Alternative Hypothesis Two-Sided
Early Stop Accept Null
Method Error Spending
Boundary Key Both
Alternative Reference 0.2
Number of Stages 3
Alpha 0.05
Beta 0.09
Power 0.91
Max Information (Percent of Fixed Sample) 103.8789
Max Information 282.9328
Null Ref ASN (Percent of Fixed Sample) 79.20197
Alt Ref ASN (Percent of Fixed Sample) 102.1476


The "Boundary Information" table in Output 110.10.2 displays the information level, alternative reference, and boundary values. With a specified alternative reference theta 1, the maximum information is derived from the procedure, and the actual information level at each stage is displayed in the table. By default (or equivalently if you specify BOUNDARYSCALE=STDZ), the alternative reference and boundary values are displayed with the standardized Z scale. The alternative reference at stage k is given by theta 1 StartRoot upper I Subscript k Baseline EndRoot, where theta 1 is the specified alternative reference and upper I Subscript k is the information level at stage k, k equals 1 comma 2 comma 3.

Output 110.10.2: Boundary Information

Boundary Information (Standardized Z Scale)
Null Reference = 0
_Stage_   Alternative Boundary Values
Information Level Reference Lower Upper
Proportion Actual Lower Upper Beta Beta
1 0.3333 94.31094 -1.94228 1.94228 -0.08239 0.08239
2 0.6667 188.6219 -2.74679 2.74679 -0.90351 0.90351
3 1.0000 282.9328 -3.36412 3.36412 -1.92519 1.92519


The "Error Spending Information" table in Output 110.10.3 displays the cumulative error spending at each stage for each boundary.

Output 110.10.3: Error Spending Information

Error Spending Information
_Stage_ Information
Level
Cumulative Error Spending
Lower Upper
Proportion Alpha Beta Beta Alpha
1 0.3333 0.00000 0.01000 0.01000 0.00000
2 0.6667 0.00000 0.04000 0.04000 0.00000
3 1.0000 0.02500 0.09000 0.09000 0.02500


With the STOP=ACCEPT option, the design does not stop at interim stages to reject upper H 0, and the alpha spending at each interim stage is zero. For the power family error spending function with the default parameter rho equals 2, the beta spending at stage 1 is left-parenthesis 1 slash 3 right-parenthesis Superscript rho Baseline beta equals left-parenthesis 1 slash 3 right-parenthesis squared 0.09 equals 0.01, and the cumulative beta spending at stage 2 is left-parenthesis 2 slash 3 right-parenthesis Superscript rho Baseline beta equals left-parenthesis 2 slash 3 right-parenthesis squared 0.09 equals 0.04.

With ODS Graphics enabled, a detailed boundary plot with the acceptance and rejection regions is displayed, as shown in Output 110.10.4.

Output 110.10.4: Boundary Plot

Boundary Plot


The following statements request a two-sided design with the BETAOVERLAP=ADJUST option, which is the default:

ods graphics on;
proc seqdesign altref=0.2 errspend;
   design nstages=3
          method=errfuncpow
          alt=twosided
          stop=accept
          betaoverlap=adjust
          beta=0.09
          ;
run;

With the BETAOVERLAP=ADJUST option, the procedure first derives the usual beta boundary values for the two-sided design and then checks for overlapping of the beta boundaries for the two corresponding one-sided tests at each stage. If this type of overlapping occurs at a particular stage, the beta boundary values for that stage are set to missing, the beta spending values at that stage are reset to zero, and the beta spending values at subsequent stages are adjusted proportionally.

The boundary values without adjusting for the possible overlapping of the two one-sided beta boundaries are identical to the boundary values derived in the first design (with the BETAOVERLAP=NOADJUST option, as shown in Output 110.10.2). At stage 1, the upper beta boundary value for the corresponding one-sided test is

theta 1 StartRoot upper I 1 EndRoot minus normal upper Phi Superscript negative 1 Baseline left-parenthesis 1 minus beta 1 right-parenthesis equals 0.2 StartRoot 94.31094 EndRoot minus normal upper Phi Superscript negative 1 Baseline left-parenthesis 0.99 right-parenthesis equals 1.94228 minus 2.32635 equals negative 0.38407

where theta 1 equals 0.2 is the upper alternative reference, upper I 1 equals 94.31094 is the information level at stage 1, and beta 1 equals 0.01 is the beta spending at stage 1 (as shown in Output 110.10.3).

Similarly, the lower beta boundary value for the corresponding one-sided test is computed as 0.38407. Since the upper beta boundary value is less than the lower beta boundary at stage 1, overlapping occurs, and so the beta boundary values for the two-sided design are set to missing at stage 1.

With the beta boundary values set to missing at stage 1 and the beta spending beta prime 1 equals 0 the beta spending values at subsequent interim stages are adjusted proportionally. In this example, the adjusted beta spending at stage 2 is computed as

beta prime 2 equals beta prime 1 plus StartFraction beta 2 minus beta 1 Over beta 3 minus beta 1 EndFraction left-parenthesis beta 3 minus beta prime 1 right-parenthesis equals 0 plus StartFraction 0.04 minus 0.01 Over 0.09 minus 0.01 EndFraction 0.09 equals 0.03375

where beta Subscript k is the cumulative beta spending at stage k before the adjustment, k equals 1 comma 2 comma 3.

The "Design Information" table in Output 110.10.5 displays design specifications and derived statistics for the design.

Output 110.10.5: Design Information

The SEQDESIGN Procedure
Design: Design_1

Design Information
Statistic Distribution Normal
Boundary Scale Standardized Z
Alternative Hypothesis Two-Sided
Early Stop Accept Null
Method Error Spending
Boundary Key Both
Alternative Reference 0.2
Number of Stages 3
Alpha 0.05
Beta 0.09
Power 0.91
Max Information (Percent of Fixed Sample) 101.9388
Max Information 277.649
Null Ref ASN (Percent of Fixed Sample) 80.56408
Alt Ref ASN (Percent of Fixed Sample) 100.792


The "Boundary Information" table in Output 110.10.6 displays the information levels, alternative references, and boundary values.

Output 110.10.6: Boundary Information

Boundary Information (Standardized Z Scale)
Null Reference = 0
_Stage_   Alternative Boundary Values
Information Level Reference Lower Upper
Proportion Actual Lower Upper Beta Beta
1 0.3333 92.54967 -1.92405 1.92405 . .
2 0.6667 185.0993 -2.72102 2.72102 -0.89469 0.89469
3 1.0000 277.649 -3.33256 3.33256 -1.93494 1.93494


The "Error Spending Information" table in Output 110.10.7 displays the cumulative error spending at each stage for each boundary.

Output 110.10.7: Error Spending Information

Error Spending Information
_Stage_ Information
Level
Cumulative Error Spending
Lower Upper
Proportion Alpha Beta Beta Alpha
1 0.3333 0.00000 0.00000 0.00000 0.00000
2 0.6667 0.00000 0.03375 0.03375 0.00000
3 1.0000 0.02500 0.09000 0.09000 0.02500


With ODS Graphics enabled, a detailed boundary plot with the acceptance and rejection regions is displayed, as shown in Output 110.10.8.

Output 110.10.8: Boundary Plot

Boundary Plot


Last updated: December 09, 2022