Uptake of treatments approved by NICE and NHS England can sometimes be slower than expected, which is frustrating for clinicians, patients, and industry. What are the roadblocks? What can be done to overcome them? Our roundtable panel discusses the issues.
The process of getting new, expensive, and highly specialised treatments to patients will always be slightly convoluted and involve significant effort for healthcare professionals and industry. The various processes have been in a state of constant change for the last decade, making it even harder for those involved to navigate the system.
The good news is that all parties are trying to work together to improve new medicines uptake so that more patients can benefit from treatments sooner. However, this will take time, so Specialised Commissioning asked a panel of experts to identify the key, practical issues currently facing professionals and patients, and suggest ways of resolving them now and in the future.
Our panel of senior professionals were chosen to reflect the makeup of stakeholders who influence access to, and prescribing of, specialist and secondary-care medicines approved by NICE and NHS England locally.
How well is the current NICE process for specialised medicines working?
Jayne Spink: Genetic Alliance’s stakeholder group and rare diseases community have serious concerns about the speed with which medicines are evaluated post-licence, which is a significant barrier in terms of patient access to OMPs. We feel that this is linked to the multiplicity of options for evaluating OMPs and their various routes, which include, but are not limited to, NICE and NHS England appraisal processes. When I asked colleagues prior to this discussion about their experiences of delays following positive NICE decisions or NHS England prioritisation judgements, their feedback was that the post-approvals system is working well, with the main barrier being the process of obtaining referrals to designated centres through appropriate patient pathways.
Are there any particular issues for rarer diseases, which are often developed by companies without resources to go through the NICE process?
Jayne Spink: Currently, only half of all orphan medicinal products (OMPs) with a licence are routinely available in England, and around a fifth have not been assessed at all. One issue is uncertainty about the route through which these products will be evaluated. The highly specialised technologies (HST) process is the route by which most products most are likely to get a positive opinion or establish an access scheme, but it is limited in terms of its capacity. However, it is important to note that not all OMPs go through NICE: many end up going through single technology appraisals (TAs) rather than the HST process, in which a positive outcome is much less likely.
There are also issues about where within the NICE structure a product is evaluated. The criteria around the HST process are so narrow that they look at the prevalence of the condition to be treated as a whole. For example, in the case of cystic fibrosis or Duchenne muscular dystrophy, the HST process looked at the total number of patients with these conditions in England, but not the subgroups amenable to treatment, which resulted in a raft of OMPs going to a single TA. The HST process is also one of the longest processes for the evaluation of OMPs after licence anywhere in Europe.
In addition, some products go through the NHS England process only, with the evidence reviewed by NICE. One problem we have encountered across the UK is that there are no fewer than 15 different ways in which OMPs are evaluated for the possibility of routine prescribing in the NHS, which leads to a great deal of uncertainty—not just for the companies, who have to compile the relevant evidence to feed those processes, but also for patient groups, because they may be less experienced in contributing to these types of decision. This is particularly true if it is the first product to treat a particular condition in terms of how best to interact with the system, provide evidence, and make the case for access.
Peter Clark: Only two routes are available to get cancer drugs into play in England: NICE’s TA system and the NHS England policy prioritisation process. Since July 2016, NICE has evaluated every cancer drug in every indication—whether for a common or a rare cancer—with the TA list for the past 18 months including drugs for very rare cancers that would never have been through the NICE appraisal process in the past.
… there are no fewer than 15 different ways in which OMPs are evaluated for the possibility of routine prescribing in the NHS …
If a licensed cancer drug is not appraised by NICE, this is not the result of omission by NICE, but reflects the manufacturer’s choice not to participate in the process. Some cancer drugs have not been appraised since July 2016 because companies have chosen not to submit to NICE, in which case NICE terminates the appraisal. NICE has also brought forward its TA process and is working with manufacturers to routinely appraise drugs before formal marketing authorisation approval is granted, so that provisional approval can be issued on the day the drug is licensed. Thus, as long as a drug is licensed, it can be approved early and has a route for entry into the NHS, because NHS England funds all drugs with positive recommendations following the NICE TA appraisal process. NICE has not changed its process and its cost‑effectiveness thresholds are the same, but the majority of medications for rare cancer indications are being approved for use within the NHS in England.
The other route, the NHS England policy prioritisation process, is admittedly too long and difficult to navigate. Some drugs are being evaluated, but the process has not been overwhelmed by dozens of requests for policy prioritisation for rare cancer indications. Furthermore, the NHS England policy prioritisation process accounts for only £25 million per year of the total NHS England drug budget of £2.2 billion to fund the indications it prioritises.
Alastair Whitington: At a recent conference, NICE explained that it will be doing a significantly greater number of assessments, and not just for drugs related to cancer. This suggests that something needs to be done in terms of prioritisation, otherwise there will be a wealth of drugs that NHS England does not have the resources or capacity to manage, which could result in a logjam if not carefully managed.
Peter Clark: The NHS England policy prioritisation process examines licensed use, for example for cancer drugs licensed prior to 2016 that were not selected for NICE appraisal. However, the NHS England policy prioritisation process also deals with off-label use, which NICE is not currently allowed to appraise, but NICE is in discussion with NHS England about this, with cancer the likely starting point, because it is the therapy area with the greatest need. Everyone recognises that formal licensing will never keep pace with potential clinical applications because of the growth of targeted treatments and the advent of genomics.
Jayne Spink: The NICE process is very transparent, with clear points of interaction and consultation with patient groups. In contrast, the NHS England prioritisation process is completely opaque for a drug that has not gone through the NICE process; consequently, patient groups do not have a good understanding about why some drugs are, for example, priority level 5 initially, but in later rounds of the process become priority level 2. Although the prioritisation mechanism is available on the NHS England website (www.england.nhs.uk/publication/methods-national-clinical-policies/), it is unclear how the judgements are made: they are made by the Clinical Priorities Advisory Group (CPAG), and can seem subjective, counter-intuitive, and a poor reflection of external views. There does not seem to be a space within the NHS England prioritisation process for evaluating and taking into account evidence submitted by patient groups and advocates, which there is in the NICE appraisal process.
Alastair Whitington: As we move forward, NICE and NHS England need to work more closely together to achieve a single unified system and transparency, so that NHS England decision-making is as transparent as NICE appraisal.
The NICE process is very transparent, with clear points of interaction and consultation with patient groups. In contrast, the NHS England prioritisation process is completely opaque for a drug that has not gone through the NICE process …
Robert Glynne-Jones: The NICE process seems to be working generally well, but I have two concerns. First, pathology is hard pressed. For example, testing for DNA mismatch repair deficiency was made routinely available for the first time in a recent multidisciplinary team meeting at my hospital, despite the fact that NICE endorsed it 20 years ago.
We have also had problems with drugs like crizotinib, which is an option for treating ROS1-positive advanced non-small cell lung cancer (NSCLC) and requires an accurate and validated laboratory assessment for ROS1 before initiation,1 but for which no funding has been specifically allocated, leading the pathologist to ask who is paying for the assessment.
In the case of testing for Lynch syndrome in colorectal cancer, there was no specific funding allocated for this, so pathology departments used to send tests to outside facilities, incurring extra costs and delays relative to testing in-house. I have a sense that district general hospitals have an issue about doing any tests that require the involvement of pathology. Confusion around pathology testing causes delays; testing is important and takes time, but it’s unclear who is responsible for it or commissions it.
… implementation of a NICE TA is often led by the oncology pharmacy team and lead cancer clinician at a trust.
Secondly, despite the creation of the Systemic Anti-Cancer Therapy (SACT) database,2 there is a lack of robust audit data on how new technologies are working in the real world outside of academic research.
What do the NHS or companies need to do to ensure implementation of a positive NICE TA and access to the drug?
Jacky Turner: According to people on the ground at trust level, approvals from NICE are coming through thick and fast, with five or six drugs a week now being approved compared with one or two a month a couple of years ago. Back then, pharmacy was able to implement prescribing of these drugs through whichever pathway worked locally—whether a patient access scheme (PAS), procurement, an electronic prescribing system, or the local governance process for prescribing drugs internally.
Now, implementation of a NICE TA is often led by the oncology pharmacy team and lead cancer clinician at a trust. There is generally a local governance process for setting up the implementation of new medicines, defined locally, to ensure that the following is in place:
- paperwork, including the Regimen Specific Protocol, which describes how the medicine is to be administered and monitored, for use by all doctors, nurses, and pharmacists caring for a patient, and the PAS
- regimen-specific prescription—it is now a requirement that chemotherapy is prescribed using an electronic system, so there is a full governance process in place to ensure that this is done correctly
- data collection for SACT, funding submissions to NHS England, and procurement systems within pharmacy.
All of these processes must be in place before a cancer medicine is implemented.
The workload across the board in terms of getting approved drugs has massively increased and includes checking the right PAS has been assigned, checking the correct NHS England approval process has been recorded (that is, whether the drug was assessed through the NHS England baseline process—for example, if it is being used in a different indication—or the Cancer Drug Fund (CDF) identification process), and completing Blueteq forms not just for drugs approved through the CDF but also for those going through baseline assessment. All of these additional processes are adding to delays in implementing newly approved drugs.
There have also been issues in communications from NHS England to trusts about decisions and funding streams, which further delay the process of implementation. NHS England used to issue Specialised Commissioning Circulars, which were available to staff working within NHS England (including cancer commissioning pharmacists). These documents, when related to medicines, specified how and when approved medicines could be used. In the past, we were told that these should not be circulated to acute trusts, but could only be used internally. Currently, Specialised Commissioning Circulars are available on the Specialist Pharmacy Website (www.sps.nhs.uk); trusts should be aware of and access this information Some trusts have had to invest in personnel with a pharmacy background rather than an accounting or data-management background because these individuals have a better understanding of the appropriate flow of paperwork and money. All the different funding streams that must be dealt with, in addition to numerous new drugs and new indications, are adding to the complexity and volume of work for pharmacy.
Alastair Whitington: When the CDF originally came into operation, it funded the acquisition cost of a drug, but not costs associated with the service delivery of that drug. Have tariffs been adjusted to cover that?
Peter Clark: The drug and delivery costs are now covered for all routinely commissioned or CDF-recommended cancer drugs. Now manufacturers also have to include the costs of diagnostic processes in TAs. This is going to become a very fast-moving field, with horizon scanning by NICE and NHS England identifying genetic tests likely to be needed in future—for example, testing for tyrosine receptor kinase fusion proteins. As a result of changes to genetic testing and how it is organised, with increased involvement of genomics laboratory hubs, NHS England is now talking to Genomics England about how these prospective tests can be included in future tumour diagnostic molecular panels, and we are trying to work together more closely to identify and solve problems.
There have also been issues in communications from NHS England to trusts about decisions and funding streams, which further delay the process of implementation.
What are the financial challenges and problems when going from NICE and NHS England approval of new medicines to delivery to patients?
Patrick McGinley: I echo the points already made, particularly the need to improve patient-flow, the number of drugs being approved, and the complexity of the approval process.
Delays are a reflection of the fact that there isn’t necessarily enough funding in the system to enact change. New approvals have an impact both on commissioners, who are responsible for funding the drug only in the approved indication, and providers, who must make changes to funding and provision to enable and monitor correct prescribing.
Financial considerations are important, and one of the primary outcomes for the SACT database is the financial outcome for the year in terms of underspend or overspend.
A Blueteq CDF request is needed to ensure that the right commissioner is charged for the right drug in the right indication, and it does inevitably slow down implementation—not just of drugs, but also of devices and other innovations. If approvals are linked to detail, such as approved indications, then providing that detail on the relevant form will tend to be dependent on individuals within the system, which in turn will become obvious pinch points.
Delays are a reflection of the fact that there isn’t necessarily enough funding in the system to enact change.
Robert Glynne-Jones: A Blueteq request only takes 5 minutes to complete, so it does not slow the process down considerably.
Patrick McGinley: That is true, but the rise in the number of newly approved drugs equates to an increase in the time required for Blueteq requests over and above that necessary 2–3 years ago, which needs to be supported. Improvements in flow in one aspect of a pathway almost invariably result in pressures downstream. The key issue here is that funding is increasingly not in the hands of accountants or administrators, which can be viewed positively, but it does mean that pharmacists are using valuable pharmacy resources to provide these data.
Peter Clark: I appreciate that the system is stretched by a proportion of approvals approaching 85% and an increasing cancer drug pipeline, with NICE appraising 40 new cancer indications in 2019. However, Blueteq registration means that we can monitor the uptake and speed of uptake for every new cancer drug that comes into play.
Nationally, every audit we have done for every drug that potentially has a high level of use (i.e. excluding medications for rarer indications, for which the number of applications per month is small and thus naturally varies) has shown so far that use plateaus within 3 months of approval. Examples include the use of pembrolizumab in the treatment of PD-L1-positive locally advanced or metastatic NSCLC after chemotherapy, pembrolizumab for untreated PD-L1-positive metastatic NSCLC, and pertuzumab as part of neoadjuvant chemotherapy for HER2-positive breast cancer.
However, plateau use is not reached within 3 months of approval in the case of drugs linked with the introduction of a molecular diagnostic, which always take more time to implement.
The speed of uptake of new cancer drugs is an incredible testament to everyone involved—commissioners, providers, oncologists, pharmacists, and nurses. Because of the NICE process, access is quick, access to funding is quick, and delivery of access remains remarkably quick, for which service providers, in all their various shapes, deserve credit.
Jayne Spink: Because there is no centralised service specification for a good proportion of rare diseases, patients may or may not be seen at a specialised centre designated for prescribing. The barrier to accessing a drug with a positive approval is a patient flow issue in terms of accessing the appropriate prescribing centre rather than a money issue.
The barrier to accessing a drug with a positive approval is a patient flow issue in terms of accessing the appropriate prescribing centre rather than a money issue.
In the past, the number of cycles undertaken by patients in trials was not necessarily reflected in the real‑life setting, with some patients only going through 30–40% of expected cycles. Is there greater consistency between expectations and what patients are receiving, or does the SACT database show that this is still an issue?
Peter Clark: No-one expects real-world practice to exactly mirror the experience in a clinical trial setting. Trials include specialised groups of patients, and also usually have clear rules for stopping treatments, including the first sign of resistance-driven progression, whereas clinicians often continue drugs—particularly immunomodulatory imide drugs—in clinical practice while the patient still derives benefit.
The CDF invests heavily in the SACT database to get CDF outcomes, and SACT data are expected to be as accurate and pristine as real-world data can be. We do not have the answer to this question yet, but we should have sufficient data going back to July 2016 in a year’s time. As an example, however, brentuximab was submitted to the CDF for the treatment of Hodgkin’s disease because its success at NICE was dependent on its efficacy as a bridge to transplant based on data from publications, but there was uncertainty around its real-world effectiveness. The bridge to transplant rate in England may be higher than the published transplant rate in various places in the country. The situation is therefore very complex. In a year, we should have good data on CDF treatment durations in clinical trials and real-life situations.
Because the CDF now covers the costs of delivery and associated genetic or molecular tests, can pharmaceutical companies do anything to speed up the process?
Jacky Turner: Pharmaceutical companies are working well with NICE and getting their portfolios and data to NICE in a timely manner because they have realised that it will ultimately reflect badly on them if they do not, which means the front-end element is working.
If 40 new drugs are going to be approved this year, that is another drug per week that pharmacists must add to the prescribing system, update an existing record for, or manufacture within the aseptic unit. Early access medicines schemes and compassionate use programmes are also adding to these pressures, particularly because they must be implemented within 30 days rather than 90 days. There is very little that pharmaceutical companies can do to improve this, but the income trusts are now getting to introduce drugs through a proper process, which should be tailored towards the people who are doing that work.
In one large trust, the number of items that the aseptic unit was making increased by 16% last year, so they needed to invest in more staff to manufacture the injections. This was outsourced, as is the case for so many trusts, but external providers and companies are themselves struggling to meet demand, which is leading to other capacity pressures. The whole process of outsourcing needs to be stabilised, with better horizon planning and investment in future capacity. We need a whole-system approach to anticipate and provide capacity before we find ourselves in a situation similar to the homecare crisis, in which different homecare companies began to develop problems and could not maintain adequate homecare delivery.
Patrick McGinley: I agree that the overall flow of approvals has improved significantly in the past 2–3 years, which has resulted in pressures related to capacity within the system. Echoing Jacky’s comments, we are at a point where we either expand our aseptic units or buy in from a market that does not have the capacity to provide what we need. With providers, commissioners, NICE, and pharmacy working together more closely, we should be able to understand future capacity for all stakeholders (see Box 1 for more information on these stakeholders) within the limits of confidentiality and commercial secrecy.
… overall flow of approvals has improved significantly in the past 2–3 years, which has resulted in pressures related to capacity within the system.
If the flow of approvals is improving, but the process is limited by what can be obtained and produced at the front line, capacity needs to be taken into consideration during appraisal. Approvals should therefore take into account and provide guidance on capacity and required resources, recognising that a specified prescribing centre may not be able to expand to the capacity required to deliver a newly approved drug. In addition, confirmation of the ability of pharmaceutical companies to supply the volumes required to all trusts would be helpful.
Jacky Turner: Following a key recommendation from Lord Carter’s report to shift the balance of activity in the pharmacy workforce,3 a review of aseptic services published by NHS Improvement in 2018 mapped the capacity within an aseptic unit.4 This review concluded that NHS aseptic facilities in England need to transform to deliver a future-ready, resilient, high-quality, safe, and efficient service.4 Box 2 summarises the key learnings.4
Patrick McGinley: This aseptic services review is a useful resource for NICE appraisals and NHS England reviews because it identifies not only the location of units, but also their capacity to increase throughput.
Does the closer relationship between NICE and pharmaceutical companies in terms of planning at the start of the process and during negotiations resolve problems further down the line because pricing deals are more straightforward?
Peter Clark: Deals are more straightforward, and pharmaceutical companies are pricing much more responsibly for a variety of reasons, including recognising that routine commissioning is the only way that they will be sure of funding, and that this requires approval from NICE. Both of these facts explain why NICE approvals have increased so dramatically over the past 2 years.
Robert Glynne-Jones: In my non-teaching clinical setting, I get an email from management on the day a drug is going to be approved by NICE to flag that it is now eligible for use, and this is often the first time I hear about the availability of a new drug for use within the NHS.
Box 1: Who are the key stakeholders in your locality involved in ensuring that specialised medicines approved by NICE/NHS England can be appropriately accessed in line with guidance?
Peter Clark: The key stakeholders from my perspective are NHS England Specialised Commissioning
(central and in the commissioning hubs), the treating hospital trust, and the oncologist/haematologist who
signs the prescription.
Patrick McGinley: The stakeholders include our pharmacists and pharmacy staff, clinicians, Service Level Agreement staff, NHS England Specialised Commissioning Director, Director of Commissioning Operations, and the CPAG.
Jacky Turner: Pharmaceutical companies, who want to see maximum uptake; NHS England, who want to ensure (and often monitor) that medicines are being used in line with the guidance issued; lead clinicians; the local chemotherapy group at a trust, who will often manage the implementation of new cancer medicine; a team consisting of members of the oncology pharmacy team, the trust finance team, and members of the information department, who ensure that the submission of data to NHS England is correct; and the Formulary Committee, a multidisciplinary group consisting of lead cancer nurses, lead oncology pharmacists, and lead oncology/haematology consultants, often with a business manager and information department lead in attendance. In acute trusts/foundation trusts in England, all NICE/NHS England-approved medicines will be published on the relevant trust’s formulary; this requires submission via the medicines evaluation process
within the organisation, which is often led by the Medicines Information Department, Chief Pharmacist, and Formulary Committee.
Box 2: Summary of key learnings from the Pharmacy Aseptic Services Review by NHS Improvement, March 20184
Adapted from: NHS Improvement. Pharmacy aseptic services review—summary of key findings. Specialist Pharmacy Service, 2018. Available at: www.sps.nhs.uk/articles/review-of-nhs-pharmacy-aseptic-services-summary-of-key-findings/
Contains public sector information licensed under the Open Government Licence v3.0 (www.nationalarchives.gov.uk/doc/open-government-licence/version/3/).
There is no formal system to identify barriers or issues for implementation, and it is left up to the clinical lead to ensure implementation, which, in some cases, has led to delays of months, even up to a year, between approval and implementation in practice.
Peter Clark: The cascade system from commissioning hubs down to clinicians and pharmacists is variable, so it is good to hear that you are receiving circulars on the day a drug is approved. The fact that NHS England has 90 days to fund a drug after a positive TA does, in itself, act as a pre-warning system with respect to non-cancer drugs. However, the CDF routinely provides funding to cover the 5-month gap after NICE recommends a cancer drug and, in providing the opportunity for that funding, the CDF is effectively putting pressure on the provision system. We cannot give advanced warning because, in effect, the first warning is when NICE issues its final appraisal determination, so the only warning is given to commissioners, who need to line everything up in terms of provision.
Robert Glynne-Jones: I understand that, but there is no provision to assess any issues that will make it difficult to introduce the drug within the trust. The lead is just expected to implement the CDF’s decision and, in some cases, particularly for rare cancers, the clinical lead is unclear, and the trust’s chemotherapy lead is often not willing to take on that responsibility.
There is no formal system to identify barriers or issues for implementation, and it is left up to the clinical lead to ensure implementation, which, in some cases, has led to delays of months, even up to a year, between approval and implementation in practice.
Jacky Turner: In some of the larger trusts, the chemotherapy lead does take on this role, and monthly meetings are held to discuss the clinical, resourcing, training, and financial implications of newly approved drugs and drugs that are likely to be approved in future. It may be that some trusts do not have a system set up to deal with new chemotherapy drug approvals. It will also depend on the lines of communication between a trust and NHS England: some larger trusts in London have direct communication with NHS England, and even have staff working across both settings, which helps with flow and implementation.
Robert Glynne-Jones: If processes have been developed to deal with this issue, it would be useful to share that best practice.
Will the new NHS Long-Term Plan and new Voluntary Scheme for Branded Medicines Pricing and Access have any impact on the process of approval or how the NHS manages issues around drugs?
Peter Clark: The answer is no, but key issues remain with respect to the contributions of industry and NICE given the accelerating pipeline for cancer. Capacity is the biggest concern because many of the new drugs do not replace but rather displace existing treatment options, and the system—whether the commissioner’s office, the provider’s office, or the clinic—may not be able to cope with the influx of new drugs. For every audit of how fast the latest drugs were implemented, we expect to see a plateau, but so far the speed of implementation is not slowing down. We can only pay tribute to those involved, but there will come a time when people on the ground cannot keep pace with the drugs pipeline.
Alastair Whitington: Workforce issues and staffing are certainly a problem, with one in 11 posts currently vacant, and this issue, which is not just limited to cancer, will only get worse as more staff leave the workforce than enter it.
Peter Clark: Anecdotal reports indicate that fewer than 50% of the staff intake in 2015 are still working in the NHS, so resourcing is going to be a perennial problem.
Summary and concluding comments by Alastair Whitington
Improvements in the format and timeframe of the NICE appraisal process have been achieved in recent years, but this has resulted in downstream issues in terms of capacity for the implementation of approved drugs within the NHS. Although the NICE TA process is open and transparent, the NHS England process often leaves prescribers and patient groups uncertain about the reasoning behind drug prioritisation decisions. NICE and NHS England therefore need to work together to offer a single, unified system with open and transparent operations. The SACT database will start to provide important information about implementation and the use of approved drugs over the next 12 months.
Overall, with significant increases in demand, it is remarkable that the NHS has stepped up to the challenge with the resources available, but the question of sustainability remains, given the ever-increasing drug pipeline and portfolio.
- NICE. Crizotinib for treating ROS1-positive advanced non-small-cell lung cancer. Technology Appraisal 529. NICE, 2018. www.nice.org.uk/guidance/ta529 (accessed 9 May 2019).
- National Cancer Registration and Analysis Service. Systemic anti-cancer therapy chemotherapy dataset. www.chemodataset.nhs.uk/home (accessed 9 May 2019).
- Carter P. Operational productivity and performance in English NHS acute hospitals: unwarranted variations. London: DH, 2016. assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/434202/carter-interim-report.pdf (accessed 19 March 2019).
- NHS Improvement. Pharmacy aseptic services review: summary of key findings. NHS improvement, 2018. www.sps.nhs.uk/wp-content/uploads/2018/04/NHSI-Aseptic-Summary-and-Findings_280318.pdf (accessed 19 March 2019).