Table 1 Applicability of recommend content of statistical analysis plans for clinical trials to observational studies

 Title and study registration

1a

Descriptive title that matches the protocol, with SAP either as a forerunner or subtitle, and trial acronym

Descriptive title that matches the protocol, with SAP either as a forerunner or subtitle, and study acronym

1b

Trial registration number

Study registration number

 SAP version

2

SAP version number with dates

Unchanged

 Protocol version

3

Reference to version of protocol being used

Unchanged

 SAP revisions

4a

SAP revision history

Unchanged

4b

Justification for each SAP revision

Unchanged

4c

Timing of SAP revisions in relation to interim analyses, etc.

Timing of SAP revisions in relation to planned repetitive analyses

 Roles and responsibility

5

Names, affiliations, and roles of SAP contributors

Unchanged

 Signatures of:

6a

Person writing the SAP

Unchanged

6b

Senior statistician responsible

Unchanged

6c

Chief investigator/clinical lead

Unchanged

 Background and rationale

7

Synopsis of trial background and rationale including a brief description of research question and brief justification for undertaking the trial

Synopsis of study background and rationale including a brief description of research question and brief justification for undertaking the study

 Objectives

8

Description of specific objectives and hypotheses

Description of specific objectives and hypotheses, including secondary objectives

 Study design

9

Brief description of trial design including type of trial (e.g. parallel group, multi-arm, crossover, factorial and allocation ratio and may include brief description of interventions)

Brief description of study design including type of study (e.g. case-control, cross-sectional or cohort study)

 Randomization

10

Randomization details, e.g., whether any minimization or stratification occurred (including stratifying factors used or the location of that information if it is not held within the SAP)

Not applicable

 Power considerations

11

Full sample size calculation or reference to sample size calculation in protocol (instead of replication in SAP)

In case of an unspecified sample size, provide power calculations for (at least) the primary analysis or present a detectable difference with a specified power*

 Framework

12

Superiority, equivalence, or noninferiority hypothesis testing framework, including which comparisons will be presented on this basis

Unchanged*

 Statistical repetitive analyses and stopping guidance

13a

Information on interim analyses specifying what interim analyses will be carried out and listing of time points

Information on repetitive analyses specifying what repetitive analyses will be carried out and listing of time points*

13b

Any planned adjustment of the significance level due to interim analysis

Any planned adjustment of the significance level due to repetitive analyses

13c

Details of guidelines for stopping the trial early

Details of guidelines for stopping the study early

 Timing of final analysis

14

Timing of final analysis, e.g., all outcomes analysed collectively or timing stratified by planned length of follow-up

Unchanged*

 Timing of outcome assessments

15

Time points at which the outcomes are measured including visit “windows”

Unchanged

 Confidence intervals and P-values

16

Level of statistical significance

Unchanged*

17

Description and rationale for any adjustment for multiplicity and, if so, detailing how the type 1 error is to be controlled

Unchanged*

18

Confidence interval to be reported

Unchanged

 Adherence and protocol deviations

19a

Definition of adherence to the intervention and how this is assessed including extent of exposure

Not applicable

19b

Description of how adherence to the intervention will be presented

Not applicable

19c

Definition of protocol deviations for the trial

Definition of protocol deviations for the study

19d

Description of which protocol deviations will be summarized

Unchanged

 Analysis populations

20

Definition of analysis populations, e.g., intention to treat, per protocol, complete case, safety

Definition of analysis populations, e.g., per protocol, complete case, safety

 Screening data

21

Reporting of screening data (if collected) to describe representativeness of trial sample

Reporting of screening data (if collected) to describe representativeness of study sample

 Eligibility

22

Summary of eligibility criteria

Unchanged

 Recruitment

23

Information to be included in the CONSORT flow diagram

Information to be included in the STROBE flow diagram

 Withdrawal/follow-up

24a

Level of withdrawal, e.g., from intervention and/or from follow-up

Level of withdrawal, e.g., dropouts after inclusion or refusal to be contacted for additional information

24b

Timing of withdrawal/lost to follow-up data

Unchanged

24c

Reasons and details of how withdrawal/lost to follow-up data will be presented

Unchanged

 Baseline patient characteristics

25a

List of baseline characteristics to be summarized

Unchanged

25b

Details of how baseline characteristics will be descriptively summarized

Unchanged

 Potential confounding covariates

–

–

A description of potential confounding covariates and how these will be dealt with*

 Outcome definitions

List and describe each primary and secondary outcome including details of:

26a

Specification of outcomes and timings. If applicable include the order of importance of primary or key secondary end points (e.g., order in which they will be tested)

Unchanged

26b

Specific measurement and units (e.g., glucose control, HbA_1c [mmol/mol or %])

Unchanged

26c

Any calculation or transformation used to derive the outcome (e.g., change from baseline, QoL score, time to event, logarithm, etc)

Unchanged

 Analysis methods

27a

What analysis method will be used and how the treatment effects will be presented

Unchanged*

27b

Any adjustment for covariates

Unchanged

27c

Methods used for assumptions to be checked for statistical methods

Unchanged

27d

Details of alternative methods to be used if distributional assumptions do not hold, e.g., normality, proportional hazards, etc

Unchanged

27e

Any planned sensitivity analyses for each outcome where applicable

Unchanged*

27f

Any planned subgroup analyses for each outcome including how subgroups are defined

Unchanged*

 Missing data

28

Reporting and assumptions/statistical methods to handle missing data (e.g., multiple imputation)

Unchanged*

 Additional analyses

29

Details of any additional statistical analyses required, e.g. complier-average causal effect analysis

Unchanged

 Harms

30

Sufficient detail on summarizing safety data, e.g. information on severity, expectedness, and causality; details of how adverse events are coded or categorized; how adverse event data will be analysed, i.e. grade ¾ only, incidence case analysis, intervention emergent analysis

Only applies when interventions are studied. Sufficient detail on summarizing safety data, e.g. information on severity, expectedness, and associations; details of how adverse events are scored; how adverse event data will be analysed and the follow-up time.*

 Statistical software

31

Details of statistical packages to be used to carry out analysis

Unchanged

 References

32a

References to be provided for nonstandard statistical methods

Unchanged

32b

Reference to Data Management Plan

Unchanged

32c

Reference to the Trial Master File and Statistical Master File

Reference to the Study Master File and Statistical Master File

32d

Reference to other standard operation procedures to be adhered to

Unchanged