Clinical Event Adjudication

Adjudication was facilitated by AWARD-Adjudicator and overseen by the Endpoint Adjudication Committee (EAC). The EAC included the Chairs of nine sub-EACs: Cancer, Cardiac, Clinically Significant Bleeding (CSB), Death, Dementia, Depression, Physical Disability and Stroke. Each sub-EAC was responsible for the adjudication of particular ASPREE endpoints (see Table 1).

Table 1. Endpoint type and adjudication outcomes, responsible sub-EAC and Chair of sub-EAC.

Endpoint Sub-EAC Endpoint outcomes
Cancer Cancer 1. Non-metastatic cancer
2. Metastatic cancer
3. Not cancer endpoint
CSB CSB 1. Clinically significant bleeding endpoint
2. Not CSB endpoint
Death Death 1. Cancer death
2. Clinically significant bleeding death
3. Coronary heart disease death
4. Stroke death
5. Dementia Death
6. Other death
Dementia Dementia 1. Dementia
2. Not dementia endpoint
Depression Depression 1. Hospitalisation for depression
2. Not hospitalisation for depression endpoint
Hospitalisation for Heart Failure Cardiac 1. Hospitalisation for heart failure endpoint
2. Not HHF endpoint
Myocardial Infarction Cardiac 1. Acute MI
2. Established MI
3. Not MI endpoint

Each endpoint case was assigned to three adjudicators (with the exception of death and dementia that were only assigned to two adjudicators) via AWARD-Data. Adjudicators assigned to an endpoint access the case summary document via AWARD-Adjudicator and independently complete a standard adjudication form. The relevant protocol definitions and decision rules were displayed on the adjudication pages to ensure adherence and standardisation. If the result of the first two adjudications was discordant, the case was automatically sent to the third adjudicator. Death and dementia were exceptions to this rule as discordance was resolved by consensus for these events. Regular sub-EAC teleconferences were held to discuss a) any ‘three-way’ discordant adjudication cases and b) special cases requested for discussion.

Some events required completion of sub-classification (e.g. cancer type for cancer). To avoid unnecessary discordance, subclassification was completed either by the first adjudicator or by the third adjudicator.

Raw adjudicated endpoint outcome data has been included in Section F2 and F3 of the ASPREE Longitudinal data set.

The derived clinical outcomes reported in the three New England Journal of Medicine papers, published in 2018, have been included in Section F1 of the ASPREE Longitudinal data set.