Rises in non-submissions to NICE: do they matter?

Leela Barham asks why companies may choose to not submit their drugs to NICE and keep them off routine commissioning – a trend that appears to be on the rise.

Appraisal of a treatment by the National Institute for Health and Care Excellence (NICE) is voluntary; companies can simply choose not to submit, resulting in a statement from NICE that the appraisal was terminated due to non-submission.

Yet this will have consequences because non-submission is looked upon dimly by the biggest buyer of specialised medicines, NHS England. Their policy is clear; their default position is not to routinely commission the treatment. Yet it is clear that companies choose not to submit to NICE, that raises questions; why and so what?

Rise in non-submissions

NICE first saw companies choosing not to submit in 2008/9 and since then more and more have taken this option. In 2019/20 close to 1 in 5 of NICE’s recommendations was a non-submission.

“Companies may simply be putting the UK further down the priority list due to Brexit. The referendum was held in June 2016; it does look like non-submissions have been going up since then”

In total, there were 54 non-submission recommendations from NICE from 2008/09 to 2019/20. The reasons for non-submission are of course not clear from NICE’s data – they will only be known by the companies involved.

The companies who have chosen to not to submit – at least at the time and in the indication being looked at by NICE and based upon the company name identified as supplying the treatment in the Electronic Medicines Compendium (EMC) – include (number of non-submission recommendations in brackets):

Amgen (3)
Bausch & Lomb (2)
Bayer (1)
BMS (2)
Boehringer Ingelheim (1)
Celgene (2)
Chiesi (1)
Eli Lilly (1)
Gilead (3)
Ipsen (1)
Janssen-Cilag (6)
Merck Serono (1)
MSD (3)
Novartis (5)
Pfizer (2)
Roche (7)
Takeda (1)

In 12 non-submissions, the company could not be identified because either there were several names in the EMC (likely because the treatment is now off patent) or were not found.

NICE introducing charges for appraisals was seen as a potential driver of non-submissions by companies according to consultants at Athena Market Access Solutions and Tolley Health Economics, in advance of their introduction. This was a concern particularly for smaller companies who may find the charges prohibitive (which in 2019/20 ranged from £22,000 to £215,000).

NICE introduced charges on the 1 April 2019. Since then there have been 10 non-submissions, but all but one of the treatments are from companies who are listed in the top 100 by revenue for 2019. This perhaps suggests that fees for small companies aren’t likely to be driving non-submissions (so far). It could also be a function of whether small company treatments are invited for appraisal; that’s something that needs more data mapping to know.

It is possible to look at some of the features of the treatments which perhaps help explain non-submissions. Of the 54 treatments, 24 (44%) are for conditions categorised as rare by Orphanet. Seventy-eight per cent are in the antineoplastic and immunomodulating agents (many of which are cancer) according to WHO’s ATC classification.

Whilst the underpinning evidence to support use of these treatments for rare conditions has not been looked at – this would after all be what NICE would have wanted to have seen if companies had submitted – it is not a stretch to think that there could be challenges in the robustness of the clinical evidence base. The challenges could be, for example, small sample sizes in trials, or single arm trials, given that many of the treatments are for rare conditions.

What could also be a factor – with the limited ability to offer different prices for different indications and/or use in combination – is the potential for companies to prefer to forgo an indication and/or combination use because it’s going to compromise revenues.

In essence, if a company has already launched and secured approval, but needs a lower price in another indication/combination, they would need to lower the price for all use under current rules.

Whilst it’s hard to know if this is the case, there are 54 non-submissions for 44 treatments that in total – including non-submissions – have 162 recommendations. This suggests that there are products that have been put through appraisal in another circumstance – be that in another position in the pathway, indication or combination – but where companies have decided not to submit in another.

It’s also true that it could be a function of the anticipated finding from NICE; NICE committees are guided not just by the clinical evidence but the value for money too. Depending upon the price being sought and the wider costs and cost offsets, companies could anticipate that they would not be able to meet NICE’s cost-effectiveness thresholds.

Of course, Brexit could play a role and companies may simply be putting the UK further down the priority list when it comes to securing market access. The referendum to leave the EU was held in June 2016; it does look like non-submissions have been going up since then.

Does it matter?

There are different schools of thought about whether non-submissions are an issue, at least from an NHS perspective. If treatments are simply not that clinically effective then arguably it’s not a big concern. If they aren’t cost-effective – at prevailing thresholds – that could be argued to mean that other, more cost-effective treatments that can generate more health for scarce NHS pounds can be bought. If it’s due to inflexible pricing rules that don’t allow for the commercial drivers it’s arguably more of an issue as there is the potential for health to be generated cost-effectively – although the counter argument to this is affordability, as different prices for different indications could add more spend to the system overall.

For NICE, non submissions are a double-edged sword; less to do, yet since they charge companies for appraisals, it also means less income. Charges are, to a degree, predicated on volumes of expected number of appraisals with fixed costs spread across appraisal activity. If NICE does far less than it expects it’s not going to successfully recoup costs. This could change charges in the future too.

From a company perspective, it does seem that companies are willing to forgo a NICE appraisal, and perhaps it doesn’t affect their reputation.

Yet, if you are the patient, it must surely be frustrating that something that could help you, and that has been approved by the regulator, isn’t going to be easily available. It means you have limited options to access the treatment, be that paying privately, relying on a clinician to apply for exceptional funding, or seeking access perhaps via ongoing trials or compassionate use from the company.

Of course, whether an issue is important enough to address also relies on the scale of the problem. It certainly looks like non-submissions are on the rise so we might expect more discussion on the issue and potential solutions – one of which could be a genuine openness to indication-based pricing – to be pushed for in the future.

About the author

Leela Barham is a researcher and writer who has worked with all stakeholders across the health care system, both in the UK and internationally, on the economics of the pharmaceutical industry. Leela worked as an advisor to the Department of Health and Social Care on the 2019 Voluntary Scheme for Branded Medicines Pricing and Access (VPAS).