Study of the aHUS Diagnosis Process- the “whys”, “whats” and “hows”

It is now over two years ago that Global Action began a major study of the aHUS Diagnosis Process, it is well over a year ago since the first report of Global Action’s Research Study of the aHUS Diagnosis Process was published. Three more reports were to follow about the experience of aHUS patients when getting an aHUS Diagnosis. The research authors look back at what they did, in an interview with twenty questions that would be asked of PhD students about their thesis.

Interviewer: Can you start by summarising your study?

Authors : Our study was about process excellence. The process being a clinical one. The diagnosis of aHUS. By mapping and measuring it and to gain insights into its quality in terms of time and outcomes. To see if, and what, improvement was needed.

What motivated you and inspired you to carry out this research?

aHUS patients. Getting the diagnosis is something they talk about when they attend any gathering of aHUS patients wherever it might be in the world. But it was an email received from the mother of a young man who struggled to get a timely diagnosis which eventually triggered the study to be carried out. It was time to collect data about the diagnosis experience of aHUS patients which was not just anecdotal.

Why is this problem you tackled worth tackling?

Because along with access to the most effective treatment, a timely and accurate aHUS diagnosis is going to result in the best of health outcomes and least treatment burden for patients. The quality of the process by which it is done determines the quality of the patient’s outcomes and the rest of their lives.

Which of these does your research address?

The process, its steps, its events and the characteristics of the patients who have gone through it and how each influence health outcomes , both physically and mentally, following an eventual diagnosis.

Which are three most important papers that relate to your study?

The first would be one about the priorities of research that matter to aHUS patients ( see HERE ) It includes questions seeking answers about the diagnosis process experience. Then it would be a poster abstract by the Lupus Foundation of America which showed us how a patient organisation could undertake its own research, particularly about getting a diagnosis. The third would the Committee on Diagnostic Error in Health Care’s report which provided us with a model of the diagnosis process which we could build our research around.

What published work is closest to yours. How is your work different?

The Lupus Foundation work is the nearest but there was little in the aHUS space which is anything like what we tried to do. We gathered data from the patients themselves and not their medical records. Probably the work of the Vande Walle group ,using some pooled data from four phase 2 trials of eculizumab, came closest to examining the impact of diagnosis timelines on patients. Clinicians can access data that we cannot.

What have been the most major developments in your area?

aHUS is no longer an orphan disease, there is an effective treatment. There are more potential treatments in the pipeline. With access to more affordable effective treatments, an excellent disease diagnosis process will be essential for realising the full benefits to patients that can come from these treatments. A rapid and accurate diagnosis for all depends on the quality of the diagnosis process.

Why did you use this research methodology? What did you not gain from it?

We have used online questionnaires before to gather information from aHUS patients around the world. aHUS is a rare disease and research often depends on finding tens of people to participate. With our social network reach we can find hundreds of patients. Enough to make the research valid. It is based , however, on participants’ best recollections of what happened not medical records. Although of course the latter source may not always be complete and accurate. But also we would have liked to have gained a greater reach to more of those 20,000 aHUS patients living in countries and parts of the world today who are not aware of us.

How have you evaluated your study ?

All the time we were undertaking it. When designing the questionnaire we were conscious of the need to keep it simple whilst aware of the complexity of a diagnosis journey. There were numerous rewrites of questions. Similarly when the data was received and sorted , there were checks and balances of the results with totals. We also compared our aHUS patient cohort’s characteristics with other global statistics and found they fell within parameters of other published reports and were not outliers. We used simple statistical techniques in our analyses to describe and assess variances and their significance. Statistical calculations were checked and rechecked!

How do you know your findings are correct?

Difficult to answer that, as no one has attempted to measure the outcomes of the aHUS Diagnosis Process in the way we have. If clinicians got together to do the same using medical records of the same patients to do the same analysis then we might know. But we acknowledged in our reported methods there might be some over estimating of timelines and under reporting of events , so we tried to make questions fully relatable to those who experienced it to help their recall.

What are the strongest / weakest parts of your study.

Collecting data for all parts of the diagnosis process was the strongest element of the research, but having so much data to report may have weakened its presentation. Having so many tables spread over four individual, but linked, reports may have detracted from focus.
The fourth report had extensive statistical significance testing of key process events and patient characteristics variables when drilling down into the influences of process outcomes for patients. That provided a strong ending for the project. It gives a weight to what people might have logically thought of influences outcomes to aHUS patients.

Our key weakness was the lack of access to an ethics committee to review and approve our objectives and methods. Not having that is a barrier to rare disease patient organisation getting research published in high profile publications. The impact was less as a result.

To what extent do your contributions generalise?

As we say in the reports of the study the participating cohort may reflect the reach and the mix of the social media used to encourage participants. The same can happen with using register data from patients living in countries where a particular aHUS treatment is sold. It may be more about the experience in the developed world. It could be argued that if a less than excellent process was found in countries with more healthcare advantages, then it is more than likely to think that elsewhere things could only be worse.

Who will be most interested in your study?

We would think aHUS patients because they have gone through the process and can relate to all of it. Clinicians with a special professional interest in aHUS and who themselves are striving to improve diagnosis process outcomes. Then other clinicians, what ever their specialism, who have a key part to play in the outturn quality of the process, even primary care / general practitioners.

What is the relevance of your work to practitioners ?

It is relevant to any practitioner who encounters rare diseases at all levels of healthcare. Some of the horses may sometimes be zebras albeit their galloping may sound the same. The study recognises the challenge that practitioners face. Out of billions of doctor/ patient consultations each year about 4000 of them will be about having to diagnose aHUS. The mother of the aHUS patient who wrote to us said that something was needed to bring attention to the disease at all health care levels The resulting study however good and relevant faces competition from a multitude of other medical matters needing attention.

What are the contributions to the knowledge of your thesis?

The study contributes substantial evidence about the impact of the aHUS diagnosis process on patients. It should be cited in any article about diagnosing aHUS to spread the knowledge and give a strong rationale for other researchers’ work to add greater knowledge. Professor Fadi Fakhouri in his plenary lecture about “aHUS in 2022” at the International Society of Nephrologists Symposium in Bergamo used an image of one of the reports we published and cited this work to illustrate that the ability to diagnose aHUS remains a priority and challenge for all clinicians.

How long term are these contributions?

It is a case of “The moving finger writes and having writ moves on “ with much of published research. It accumulates longevity through citing in other published research and referencing at talks. The mother of the patient who wrote to us thought that a TED talk would be a way to go. It would be timeless.But a charismatic presenter who can sum it all up in a 10 to 15 minutes talk is yet to be found.

What have you learned from the process of doing your research?

If we did something like this again it would be with the knowledge that there is little support for patients undertaking their own research from the established research publication platforms. It was disappointing that a journal supposedly having a specific interest in rare diseases offered no help when asked for it. We have found a potential ethics committee since the research had been done but despite asking around there was nothing available to us at the time we needed it. We also know there is an industry of article writing specialists , supplying services which cost many , many thousands of pounds. Too much for volunteers and then meeting journal specifications requires skills way beyond what you would expect.

What advice would you give to other researchers entering this area?

Be clear about what you want your study to achieve before you start. Ours was about finding the quality of a process not about creating clinical guidelines to use. Inevitably such clinical details came into it. So the most obvious one is to read as much as you can about the subject before you start designing anything.

Do you propose further research? How would you start this?

After two years of labour to produce the four reports coming out of our study it is perhaps too soon to say whether we would do it again and in that way. However there are research topics which still matter to aHUS patients, and which, if we did not look into them , it is unlikely that any one one else would too. It is getting answers for aHUS patients that it is the motivation and would be the starting point of any future research.

But when all is said and done there is a personal satisfaction from doing something like this. Not just the authority it adds to your personal patient advocacy. Performing many of the tasks that you have seen in other people’s published research, you have a greater appreciation of what others have done. But also what you have done well too. Other patient advocates should try it for their personal growth as aHUS patient advocates.

Article No. 556

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