This post is part of a series of articles for Rare Disease Day exploring the work in which BRC-funded researchers are involved. You can find our other articles here.

As part of our Rare Diseases Day celebration, the team from King’s Technology Evaluation Centre (KiTEC) will be in St Thomas’ Hospital on Wednesday 28 February talking about the research they’re doing to help make new treatments available to patients with rare diseases.

We caught up with Dr Anastasia Chalkidou to talk about the innovative methods her team are using to overcome the challenges of rare disease research.


Hi Anastasia, tell us about your team’s work

At KiTEC we evaluate whether or not there is enough evidence to show a technology or a pharmaceutical will benefit patients. When the answer we get is that there isn’t enough evidence either way, we work with clinicians on a study design to generate that evidence.

One of the ways we do this is through a national programme called Commissioning for Evaluation. We are currently running three of these programmes, and the one we are discussing today is looking at using a cancer drug called rituximab to treat idiopathic membranous nephropathy (IMN) which is a rare disease. In patients with IMN, their immune system produces antibodies that attack their kidneys. This means they gradually lose kidney function and end up needing to have a transplant or dialysis.

So this drug is currently used for blood cancers and there is some evidence suggesting that there is benefit for IMN patients. But in order to get that treatment regularly funded in the NHS there needs to be robust evidence saying that it helps IMN patients to improve their renal function or to delay the decline in their renal function.

The patients are aware that this treatment is not funded regularly for their disease. So NHS England makes that drug available for a certain number of patients, with the requirement that these patients offer their clinical data back. This means NHS England can see if there is evidence of benefit, that it’s a good use of tax payers’ money and that it’s safe to give to these patients. This is an already licensed drug, not an experimental treatment, but we’re giving it to a patient group that don’t routinely take it, so you have to monitor for anything unexpected that you haven’t seen before.

Do they know why rituximab might work for IMN?

It’s an immunomodulatory therapy, which means that it affects the way that immune cells in a patient’s body works. In IMN, a type of immune cell called lymphocytes produce antibodies that attack the kidney – they shouldn’t be doing that. Rituximab affects those lymphocytes so they don’t produce antibodies to attack.

There is some evidence that it helps IMN patients, from small observational and randomised control trials in patients with IMN. They haven’t been done in the UK though, and when you test a treatment it’s important to test it in the country-specific setting. There certainly isn’t enough evidence for NHS England to fund the treatment.

What sort of difficulties do you face researching a rare disease like this?

For rare diseases, it’s really difficult to collect evidence because you won’t have many patients, so you need a lot of centres to contribute, to access the number of patients you need. It’s almost impossible in some cases to do a randomised control trial. The standard treatment at the moment is a drug regimen called ‘modified ponticelli’, and a randomised control trial in the UK for that took 10 years.

So you need to have a method of collecting evidence that provides you with access to multiple centres and allows you to collect evidence for years, in some cases decades. That’s why more and more national databases are being set up. This approach tries to use clinical data already generated within the NHS that we can then capture through a registry and use that process to gather evidence.

For kidney disease, there is a national registry called RaDaR (national registry of rare kidney diseases). It’s a database that clinicians and patients can access and upload patient data. In most cases these are identifiable data so researchers must comply with a very strict set of regulations. When these patients are approached to take part in the scheme they are asked if they are happy for their identifiable date to be stored, if they’re happy for their data to be shared with a research group and whether they are happy for their data to be linked to other datasets.

Apart from RaDaR, researchers use the Hospital Episode Statistics database and the Office for National Statistics. These are national registry databases that continuously upload patient data from anyone who visits the hospital. For us to do this kind of research, we need to identify a patient dataset in one registry and link that data, using their NHS number for example. Then you have a network of information that you bring together and you can generate evidence. Some people might have questions about whether that can provide evidence that is as good as a randomised control trial, but that’s not the only way to get robust evidence.

Would this be possible in other countries that don’t have a national health service?

No, I don’t think so. One problem is that you might not have a uniform setting for the care provider – you might have a hospital with a doctor performing a treatment for IMN patients, and then another hospital that offers their care slightly differently. When you run a trial, it is set up so that these biases are eliminated and you just see the effect of the treatment. But when you don’t have that, you need to minimise the bias by ensuring the care provided is consistent. So I think the NHS is an ideal setting to do this type of research, especially for rare diseases.

Thinking about rare diseases day – why is it important to you to be supporting?

For us, it’s important for patients and staff and people visiting the hospital to know that this scheme exists. It’s important for us to raise awareness that the scheme offers treatment that wouldn’t otherwise be available to these patients, that this is an alternative way to generate this kind of evidence that is less well known about.

In order for Commissioning for Evaluation to be successful, and of benefit to patients in the future, those patients taking part now need to offer their data. We find that patients are very happy to do that.