Section F
Section F contains all endpoint data collected during ASPREE as well as the derived clinical outcomes reported in the trio of papers published in the New England Journal of Medicine in 2018 (1, 2, 3) which represent the main findings of the ASPREE study.
F.1 Primary and Secondary Endpoint Data from 2018 New England Journal of Medicine Papers
Description
This section contains the derived clinical outcomes reported in the trio of papers published in the New England Journal of Medicine in 2018. The study’s primary endpoint was death from any cause or incident dementia or persistent physical disability. Secondary endpoints included:
- Cancer
- Cardiovascular events (specifically hospitalisation for heart failure, myocardial infarction and stroke)
- Death from any cause
- Dementia
- Depression
- Major haemorrhage (including clinically significant bleeding events and haemorrhagic strokes)
- Mild cognitive impairment
- Physical disability
Data presented in this section have been derived using adjudicated primary endpoints and relevant secondary endpoint data. Physical disability endpoints confirmed using the modified list of Katz ADLs did not require adjudication and have been used to derive variables in this section.
Timing of Data Collection
Following randomisation, primary and secondary endpoint data was collected bi-annually (at the annual visit and at the six-month phone call). Participants were also able to contact ASPREE at any time and report a clinical event. Death could be detected at any point in time. In Australia, linkage with the Ryerson Index of obituaries was performed on a weekly basis to detect deaths. A search of the National Death Index (NDI) was conducted in both countries in November 2017. Following report of a clinical event, supporting documentation was collected and cases were adjudicated. See Study Endpoints for more detail.
Summary of Data Dictionary
This section contains nominal and discrete data. Nominal data regarding the occurrence of these clinical outcomes have been presented alongside the event “days since randomisation” to indicate when the event occurred. Information has been provided in the data dictionary to reflect which of the three papers each variable was used in. All commentary codes in this section are 0 to indicate that data is in range and has been provided.
F.2 All Endpoints
Description
This section contains all adjudicated primary and secondary endpoints (including endpoints where the ASPREE endpoint protocol criteria were not met). Relevant supporting documentation was sought for all primary and secondary endpoints and cause of death, and cases were subsequently adjudicated by a panel of clinical experts. Physical disability endpoints confirmed using the modified list of Katz ADLs did not require adjudication and are included in this section.
Timing of Data Collection
See timing of F.1 Primary and Secondary Endpoint Data above.
Summary of Data Dictionary
This section contains nominal and discrete data. Nominal data regarding the type of clinical event as well as the adjudication outcome of each event have been presented. The event “days since randomisation”, which indicate when an event occurred, has been presented for events which met the ASPREE endpoint protocol criteria.
F.3 Adjudicated Primary and Secondary Endpoints
Description
This section contains all adjudicated secondary endpoints. Relevant supporting documentation was sought for all secondary endpoints and cases were subsequently adjudicated by a panel of clinical experts. Physical disability endpoints confirmed using the modified list of Katz ADLs did not require adjudication and are included in this section. Data regarding the timing of the last endpoint screen has also been provided for each participant as the “days since randomisation” for each participant who withdrew from the study.
Timing of Data Collection
See timing of F.1 Primary and Secondary Endpoint Data above.
Summary of Data Dictionary
This section contains nominal and discrete data. Nominal data regarding the occurrence of and type of all primary and secondary clinical events have been provided for each participant alongside the event “days since randomisation” to indicate when an event occurred. Each variable is linked with a commentary code that aims to provide additional data with regard to missing data, out of range data, alterations to data collection methods and other special considerations. A commentary code of 3 has been applied to indicate when a field is not applicable to the participant. For example, if a specific secondary endpoint was not reached by a participant then details relating to that secondary endpoint are not applicable.
F.4 “Hospitalisation for Reasons Other Than” Endpoints
Description
This section contains data regarding hospitalisation for reasons other than a primary or secondary endpoint. Supporting documentation (i.e. discharge summaries) were collected for each hospitalisation and were reviewed by medically trained staff within the ASPREE Endpoint team. The date of hospitalisation and a MedDRA code for the primary reason for hospitalisation was recorded in the ASPREE Web Accessible Relational Database (AWARD)-Data module. See Data Collection for more information on the AWARD suite.
Timing of Data Collection
Following randomisation, data regarding hospitalisation for other reasons were collected bi-annually (at the annual visit and at the six-month phone call). Hospitalisation data for the first 14 months of ASPREE-XT were captured retrospectively.
Summary of Data Dictionary
This section contains nominal and discrete data collected during the ASPREE Clinical Trial. Data on hospitalisation for reasons other than a primary or secondary endpoint from the Bridge period and ASPREE-XT will be prepared and released at a later date. Nominal data regarding the MedDRA code for hospitalisation have been provided alongside the event “days since randomisation” to indicate when the hospitalisation occurred.
F.5 Derived Endpoints
Description
This data set is an extension of Section F1 and contains the same derived clinical outcomes using current Section F2 data from the ASPREE Clinical Trial, the Bridge and the ASPREE-XT study up to the participant’s fourth ASPREE-XT annual visit date (XT04).
Timing of Data Collection
See timing of F.1 Primary and Secondary Endpoint Data above (although data collection is extended to XT04). Also note that additional NDI linkages were conducted in Australia in 2019, 2020 and 2022.
Summary of Data Dictionary
See the summary of F.1 Primary and Secondary Endpoint Data above.
References
- McNeil JJ*, Woods RL*, Nelson MR, Reid CM, Kirpach B, Wolfe R, Storey E, Shah RC, Lockery JE, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Ryan J, Radziszewska B, Grimm R & Murray AM, on behalf of the ASPREE Investigator Group (* joint first authors). Effect of aspirin on disability-free survival in the healthy elderly. NEJM. 2018;379:1499-1508. doi: 10.1056/nejmoa1800722
- McNeil JJ*, Nelson MR*, Woods RL, Lockery JE, Wolfe R, Reid CM, Kirpach B, Shah RC, Ives DG, Storey E, Ryan J, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Radziszewska B, Grimm R & Murray AM, on behalf of the ASPREE Investigator Group (* joint first authors). Effect of aspirin on all-cause mortality in the healthy elderly. NEJM. 2018;379:1499-1508. doi: 10.1056/NEJMoa1803955
- McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, Reid CM, Lockery JE, Kirpach B, Storey E, Shah RC, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Johnston CI, Ryan J, Radziszewska B, Jelinek M, Malik M, Eaton C, Brauer D, Cloud G, Wood E, Mahady SE, Satterfield S, Grimm R & Murray AM, on behalf of the ASPREE Investigator Group. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. NEJM. 2018;379:1499-1508. doi: 10.1056/nejmoa1805819