Article No. 327
5 March 2020
In the first part of the “How are you doing?” series about the important role that patients can play in the Alexion aHUS Patient Registry, we explored the topic of long term observations of what it is like to live after a diagnosis of aHUS. Patient Reported Outcomes (PROs) provide important data about what the patient is thinking and feeling over time. But that is true only if PROs are reported and shared on a regular basis.
In Part 2 the results of data, which the aHUS alliance Global Action team sought from the Registry about non compliance in providing PROs , is presented and considered.
| Year of enrolment | No. of new patients enrolled in year | No. of new patients completing at least one Fatigue form | Total No. Fatigue forms completed | No. new patients completing at least one general questionnaire | Total No. of general questionnaires completed |
| 2012 | 21 | 20 | 23 | 19 | 22 |
| 2013 | 336 | 279 | 353 | 290 | 369 |
| 2014 | 310 | 269 | 384 | 271 | 387 |
| 2015 | 380 | 298 | 402 | 300 | 408 |
| 2016 | 385 | 292 | 394 | 303 | 407 |
| 2017 | 317 | 222 | 291 | 236 | 323 |
| 2018 | 40 | 25 | 36 | 25 | 37 |
| 2019 | 32 | 19 | 23 | 22 | 26 |
| Total | 1821 | 1426 | 1910 | 1473 | 1988 |
Table 1 : PROs completed by newly enrolled patients ( supplied by Alexion aHUS Registry)
From 2012 ( the year the Registry began) until 2019, 1821 aHUS patients were enrolled in the Alexion aHUS Registry.
In 2018, Alexion decided to remove “uneconomic” sites, limit the number of aHUS patients to be followed and stop new patient recruitment in most countries and thereby downsize the Registry to about 900 patients (at Feb 2019) . Recruitment since 2018 has only been undertaken in Belgium, France, Poland and South Korea. New patient enrollment numbers have therefore reduced dramatically.
There are two sources of data for PROs , a universally adopted Facit- Fatigue form and a General Questionnaire about patient health and activity. Together they provide the measures for PROs.
In Table 1 information is given for the number of patients enrolled in each calendar year, the number of those patients supplying one or more of each PRO and the number of each PROs received.
Following 2012, the number of new patients enrolled grew until recruitment began to slow in 2017 and then drop sharply after Alexion’s recruitment policy change. Naturally similar trends can be seen in the numbers of PROs provided.
In no year do all newly enrolled patients complete both PROs and in the eight years only 1426 out of 1821 enrolled patients had completed a fatigue form, and slightly more , 1473 out of 1821 completed the general questionnaire.
The number of PROs entered however is higher than the number of patients enrolled, so some patients had provide 4 PROs in the calendar year. Overall there were 1910 and 1988 of each PRO entered from 1821 patients. Slightly more than the average to be expected of one of each PRO per patient in the year of enrollment.
But that is the overall perfomance for the eight years., In Table 2 the percentage of patients complying in each year and the average PROs they complete are shown.
| Year of Enrolment | % of new patients completing one Fatigue Form | Average Fatigue forms completed per patient | % of new patients completing at least one questionnaire | Average general questionnaires completed per patient |
| 2012 | 95.2 | 1.10 | 90.5 | 1.05 |
| 2013 | 83.0 | 1.05 | 86.3 | 1.10 |
| 2014 | 86.8 | 1.24 | 87.4 | 1.25 |
| 2015 | 78.4 | 1.06 | 78.9 | 1.07 |
| 2016 | 75.8 | 1.02 | 78.7 | 1.06 |
| 2017 | 70.0 | 0.92 | 74.4 | 1.02 |
| 2018 | 62.5 | 0.90 | 62.5 | 0.93 |
| 2019 | 59.4 | 0.72 | 68.8 | 0.81 |
| Total | 78.3 | 1.05 | 80.9 | 1.09 |
Table 2: Comparison of relative PRO compliance per calendar year.
Table 2 reveals 2012 was an exemplary year for PRO compliance. Although not 100%, performance was still above 90% for both PRO versions. However as the number of patients enrolled increased in subsequent years, the percentage of new patients completing PROs , apart from in 2014, drops significantly, even more so in 2018 and 2019.
By 2017 only 70% of new patients were completing the Facit Fatigue form on enrollment and 74.4% were completing the general questionnaire. In 2018 and 2019 after the change in enrollment policy, non compliance increased and compliance was in the 59% to 69% range.
Excluding 2014 , a similar fall in the average number of PROs completed per patient can be found and by 2017 the number dropped below an expectation one of each PRO version. Once again there were even bigger reductions in 2018 and 2019 , when it perhaps could have been expected that there would be an improvement in PRO compliance because patient numbers enrolled were nearer to the 2012 levels when compliance was at its highest.
The data in Tables 1 and 2 is restricted to what happens to PROs at the beginning of a patient’s participation in the Registry. It does not reveal what happens as the patient’s participation continues into subsequent years. It cannot be concluded therefore whether there is any improvement with more experience, or a greater fall off of compliance as the novelty and enthusiasm of joining the Registry wears off, or a habit of non compliance is embedded.
What is revealed however is that, as the years have gone by, newer patients are less likely to provide PROs. This deterioration in compliance could impact on the quality of the Registry data . Their PROs at enrollment are doubly important as they set a benchmark at a time when they may be at their illest.
395 in total did not meet their obligations in their enrollment year, and although they may provide PROs later, they cannot go back to that important moment. They may even be more likely to not provide PROs in the future.
In Part 3 of “How are you doing?” the implications of an increase in non compliance with PRO obligations will be discussed and how the current trend might be reversed.
Click HERE to go to Part 1 or HERE to move on to Part 3.
