Category Archives: NICE

NICE ‘considering’ evidence to cut treatment threshold for hypertension

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NICE is considering new evidence which led to drastically lowered hypertension thresholds in the US.

The clinical advisory body, which is currently reviewing UK hypertension guidelines with a view to updating them in August 2019, told Pulse the reviews were ‘asking the same questions’.

The new US guidelines, published by the American Heart Association, decreased the threshold for stage one hypertension from an average systolic blood pressure of 140 to 130 mmHg, and from ≥160 to ≥140 mmHg for stage two.

Researchers said the changes could mean an extra 14% of people were diagnosed with hypertension, which would bring the total number to 46% of the country’s population.

The change was prompted by the 2015 SPRINT study, which showed that by treating patients with a target blood pressure of 120 mmHg, rather than the 140 mmHg target, mortality and cardiovascular events were significantly reduced.

When asked whether the changes brought in the US would be considered in the updated UK guidelines, a NICE spokesperson said: ‘Yes, we are asking some of the same questions being considered in the US and in doing so will be considering some of the same evidence.’

Current NICE guidelines define stage one hypertension as an average blood pressure of 135/85 mmHg or higher, and stage two as 150/95 mmHg or higher. It states that doctors should ‘offer antihypertensive drug treatment to people of any age with stage two hypertension’.

If the UK were to follow the US example, many patients currently defined as having stage one and treated with lifestyle changes could be pushed into stage two and medicated.

But this comes as last year, a meta analysis of 24 studies found that the evidence for reducing blood pressure targets to below 140 mmHg in over-60s was inconsistent.

The paper said that although lowering the targets could be beneficial, they could also be linked with a higher medication burden and an increased risk of short-term issues, such as hypotension.

Cardiology expert Dr Chris Aden, a GP in Southampton, said: ‘It’s going to be challenging in terms of the numbers they’re suggesting.

‘I think it’s down to good clinical common sense in how we apply it, particularly in the elderly or more frail groups’.

RCGP chair Professor Helen Stokes-Lampard said: ‘Lowering the threshold for making the diagnosis of any condition is a significant decision, that will affect thousands, if not millions of patients, and must not be taken lightly.’

‘One concern GPs already have is overdiagnosis – where we are giving a label to a situation thereby medicalising it, and prescribing medications when the benefits to the individual patient may be very limited.

‘This can be harmful for patients both in terms of causing unnecessary anxiety, and in terms of taking medication that they might not need.’

Pulse revealed in 2016 that new evidence including the SPRINT trial had prompted NICE advisors to consider updating hypertension guidelinesfor the first time since they were published in 2011.

Hypertension guidelines in full

New US classification

Normal <120/80 mmHg

Elevated 120-129/<80 mmHg

Stage 1 hypertension 130-139/80-89 mmHg

Stage 2 hypertension ≥140/90 mmHg

Current NICE guideline

Stage 1 hypertension – Clinic blood pressure is 140/90 mmHg or higher and subsequent ambulatory blood pressure monitoring (ABPM) daytime average or home blood pressure monitoring (HBPM) average blood pressure is 135/85 mmHg or higher

Stage 2 hypertension – Clinic blood pressure is 160/100 mmHg or higher and subsequent ABPM daytime average or HBPM average blood pressure is 150/95 mmHg or higher

Severe hypertension – Clinic systolic blood pressure is 180 mmHg or higher or clinic diastolic blood pressure is 110 mmHg or higher


Blood test could predict response to breast cancer drug early

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A new study has found that a blood test for cancer DNA could predict if a woman is responding to the new breast cancer drug palbociclib, months earlier than current tests.

Scientists from The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, say the test could detect in two to three weeks whether the drug is working, although they caution that the results need replicating before they are used clinically.

The research, published today in the journal Nature Communications, was largely funded by the Medical Research Council (MRC). The researchers tested women with oestrogen receptor positive breast cancer – the most common kind – who were taking part in a clinical trial of palbociclib for advanced breast cancer.

In November 2017, palbociclib was approved for use on the NHS by NICE for women with previously untreated advanced breast cancer.

Currently, women must wait two to three months to find out if palbociclib is working, via a scan.

The new blood test instead looks for circulating tumour DNA – fragments of DNA shed by the cancer that have entered the bloodstream. The DNA mutations associated with the cancer can be detected in these samples.

The researchers found that they could predict if the palbociclib treatment would work by comparing the amount of a gene PIK3CA detected in a blood test before treatment and 15 days after starting treatment. In the study, 73 women had the PIK3CA mutation and were given blood tests before and after starting palbociclib treatment.

In these women, the researchers found that those who had a small decrease in PIK3CA circulating DNA at 15 days had a median progression-free survival (the length of time the patient survived and the cancer did not get worse) of only 4.1 months, compared to women with a large decrease in PIK3CA, who had a median progression-free survival of 11.2 months.

The test could allow the women in the first group for whom the treatment is not as effective to be identified early, so that they could consider altering their treatment.

Professor Nicholas Turner, senior author and Professor of Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said: “Palbociclib is one of a new class of drugs that delays cancer progression for patients with advanced breast cancer, but it’s not effective for everybody. The problem is we have to wait for two to three months before doing a scan to see if the therapy is working.

“Our new study found that a blood test for cancer DNA in the first two weeks of treatment indicated whether the drug was likely to be effective. Having an early indication of how likely a treatment is to work might allow us to adapt treatment – switching some patients to an alternative drug that is more likely to benefit them.”

Dr Nathan Richardson, Head of Molecular and Cellular Medicine at the MRC, said: “This study provides early evidence that might help us understand sooner when a drug is successfully treating breast cancer, and if not, it can be discontinued and better approaches pursued.”

The research also received funding from the charity Breast Cancer Now and the pharmaceutical company Pfizer.


How can pharma navigate the complex marketing landscape?

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The first chapter of pharma’s commercial evolution takes us from the insatiable sales-drive of the 1980s to the present, highly complex marketing landscape.

It is easy to forget that our competitive industry still has 80-90% gross margins and, as a consequence, its traditional commercial model is driven by sales growth, rather than worrying about costs.

Under most circumstances, incremental sales drive incremental profit. Within the affiliates this is obvious, and country managers have often resisted attempts by corporate counterparts to take a centralised approach to sales and marketing, claiming their country’s commercial ecosystem is unique and not amenable to meddling.

Of course, the modern pharma company will also have to conduct market access, medical education and phase IV studies within its affiliates, but the reality is that most affiliate activity is focused on sales. For large pharma companies the sales and marketing budget usually beats R&D budgets by 1.7 times, and this is becoming increasingly difficult to justify.

Rise of primary care dominance

Throughout the 1980s and 90s the focus on sales-driven growth led to the evolution of some very different ways of working within primary care, from co-promotion and co-marketing with embedded local players, to the ‘petal’ system of multiple salesforces detailing overlapping product ranges.

The purpose of these techniques, together with employment of contract sales teams, was a sort of ‘shock and awe’ strategy which swamped the physician with frequent visits about particular products. The competitive response was usually swift and commensurate, resulting in a commercial arms race between players within a hotly contested therapeutic area.

This was known as the ‘share of voice’ model, and when applied to large primary care categories, it drove top line growth so successfully that governments and institutional payers were forced to find a response to escalating drug bills around the world.

Backlash from health technology

This response varied from country to country, but has taken two main forms; the Health Technology Assessment response and the consolidated payer response. Throughout the 1990s and 2000s, in the UK (NICE), much of Europe, Australia and parts of Asia, there has been systematic developing of a process that assesses whether a product represents value for society.

Much of the health economics work is shared among countries, and pricing comparisons made between the same product in different countries are routine. The benchmarks for the monetary value of a healthy human being are the subject of debate, but are necessary to make budgetary choices in a system without unlimited resources.

The consolidated payer model, operating in the US through pharmacy benefit managers such as Express Scripts, relies on large payers exerting pressure on manufacturers for rebates, with some undifferentiated product portfolios having to rebate as much as 50% of their gross price.

The impact of health technology assessments can be seen today, manifesting itself in pricing pressure, therapeutic substitution, a diminution of decision-making by physicians and a conscious shift towards products with a confirmed medical need. A decline in R&D productivity, however, has not made this process easy.

Dead end: Primary care hits a wall

Many commentators blame the decline in R&D productivity for the steep fall in product approvals through the 2000s but, in reality, there have been several forces at work.

The rise in genomics, together with high-speed screening techniques, led to a belief that chemical libraries could be screened against unprecedented targets and that optimised drug candidates would flood through the discovery phase into phase I trials.

The sharp product rise in the early clinical phases then came to a shuddering halt during phase II ‘proof of concept’ studies, when large numbers of clinical failures unveiled the reality – there is no short cut to understanding disease biology.

As research cul de sacs were explored, a squeeze on primary care products began in the form of price pressure from above and greater safety demands from below. As a consequence, and aided by the rise in technology, a rapid increase in the proportion of newly-approved, biological in origin drugs commenced.

Monoclonal antibodies, vaccines, enzyme replacement therapy and other therapeutic peptides, aided by insatiable demand for insulin, developed strong sales and completely changed the nature of commercial interfacing with physicians.

Biologicals change the commercial dynamic

The pressure on primary care products, together with the impact of the patent cliff in 2012/13, have combined to drive sales of primary care products into stagnation. Much of industry downsizing, particularly within commercial operations, has been in response to this.

Perhaps most merger and acquisition activity within pharma also has its origins in this relentless pressure on primary care sales and the need to reload the pipeline quickly with biologicals and specialties.

The success of biologicals and other specialties, such as oral cancer drugs, in terms of both approval and sales, has required the industry to change its commercial emphasis. The huge traditional focus on primary care or family doctors has changed to specialists, and their support workers within a secondary care or hospital environment.

The increased complexity of the specialty sell, sometimes involving multiple decision-makers, formulary approval, health economic arguments, companion diagnostics and performance-related reimbursement, has required a much smaller, but more skilled group of people to interface with the healthcare network.

Many companies have yet to find the necessary mix of skills within their workforce and are still working under the old assumptions that spending on promotional activities can remain as high as it used to be under traditional models. They do so at their peril. Check out Part 2in the next issue, as promotional resources and modern data come under intense scrutiny.


Eisai disappointed after NICE rejects earlier use for breast cancer drug

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Eisai has been dealt another disappointment from NICE, which says its breast cancer drug Halaven should not be regularly used on the NHS.

The company noted that the Halaven (eribulin) continues to be available for patients in third line – but more recently NICE had been assessing the drug after one chemotherapy regimen.

In the final guidance NICE said it was unclear whether a 4.6 month overall survival increase compared with capecitabine chemotherapy was down to treatments given after Halaven.

NICE noted that the drug did not increase progression free survival compared with chemotherapy, and that Halaven therapy is usually stopped once the disease progresses.

The uncertainty caused means that the cost per Quality Adjusted Life Year for Halaven in this use is around £69,800, according to NICE’s calculations.

This is too expensive for the NHS, even though NICE has extra leeway above its usual £30,000 threshold.

But Gary Hendler, Chief Commercial Officer Eisai Oncology Business Group, and chairman and CEO Eisai EMEA said he was “disappointed” after another knock-back from NICE.

Although NICE recommended funding for Eisai’s Lenvima (lenvatinib) in thyroid cancer last month, this was after a wait of more than two years primarily because of a change to the way NICE and the Cancer Drugs Fund are organised.

Halaven was also removed from the Cancer Drugs Fund under previous arrangements in 2015 because it was overspent. However this decision was eventually reversed and the drug was eventually rubber-stamped for regular NHS funding in late 2016.

Hendler said in a statement: “Eisai is yet again extremely disappointed with a decision from NICE. Metastatic breast cancer patients can only currently access a limited number of new treatments in England, and as eribulin has been shown to significantly improve overall survival in women with this disease it is an important option that they should have access to as early as possible.”

“Denying earlier access to it for these patients will affect their outcomes and as a company focused on making a positive difference to the lives of patients and their families, NICE’s decision concerns us greatly. Thankfully patients can still access eribulin in the third line.”

Eisai, which has built a multi-million pound manufacturing base in Hertfordshire, has threatened to stop investing in the UK because of difficulties getting drugs reimbursed.

This is despite pharma-friendly initiatives such as tax breaks on drugs that are developed and manufactured in the UK.


NICE bars NHS access to Lenvima, Nexavar for thyroid cancer

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NHS treatment cost regulators have published draft guidelines rejecting funding for Eisai’s Lenvima and Bayer’s Nexavar for treating certain patients with thyroid cancer.

The decision relates to advanced differentiated thyroid cancer that has spread to other parts of the body and cannot be operated on, in adults whose disease does not respond to radioactive iodine.

The committee heard that thyroid cancer is rare, and that the only option for patients unable to receive treatment with  Lenvima (lenvatinib) or Nexavar (sorafenib) is best supportive care.

In the draft guidelines, NICE notes that both drugs are effective in delaying disease progression compared to best supportive care, but says there is some uncertainty in establishing longer term survival.

The committee concluded that the incremental cost effectiveness ratios (ICERs) were “considerably higher” than what is normally considered to be cost effective to recommend for routine NHS use, but could not provide more specific details as the exact figures are commercially sensitive.

Also, as there are no ongoing clinical trials which might provide more evidence on overall survival benefit, the drugs could not be considered for inclusion in the Cancer Drugs Fund (CDF) either.

Approximately 3,400 people are diagnosed with thyroid cancer each year.


NICE nod for GSK’s ‘bubble baby syndrome’ gene therapy

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The National Institute for Health and Care Excellence has published draft guidance recommending GlaxoSmithKline’s gene therapy Strimvelis as an option for treating an ultra-rare immune deficiency condition commonly referred to as bubble baby syndrome.

Severe combined immunodeficiency due to adenosine deaminase deficiency, or ADA-SCID, is an inherited genetic condition affecting the body’s white blood cells that renders the body’s immune system unable to function properly, leaving patients at high risk of developing life-threatening, recurrent infections.

Around three babies a year in England are born with ADA-SCID. If left untreated, quality of life is affected by developmental delay, chronic diarrhoea, failure to thrive and recurrent infections, and infants die before school age.

The current treatment for the condition is a stem cell transplant, which can restore the immune system if successful but carry a risk of mortality and graft versus host disease. Also closely matched stem cell donors are hard to find.

Strimvelis is a gene therapy in which a patient’s bone marrow cells are removed and modified outside the body to produce working ADA enzyme, and then reintroduced via an infusion drip into a vein. The draft guidelines recommends Strimvelis when no suitable matched related stem cell donor is available.

Costing 594,000 Euros, the treatment is usually given once only and the effects are thought to be life-long, NICE said. Also, as Strimvelis has to be administered at a hospital in Milan, people will travel to Italy to have the treatment, as part of their care provided by the NHS, it noted.

“Strimvelis represents an important development in the treatment of ADA-SCID, offering the potential to cure the immune aspects of the condition and avoid some of the disadvantages of current treatments,” said professor Carole Longson, director of the centre for health technology assessment at NICE.

“This means that children born with ADA-SCID will now have a better chance of being able to lead as near normal a life as possible, going to school, mixing with friends, free from the constant threat of getting a potentially life-threatening infection.”


NICE no for Opdivo in urothelial carcinoma

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The National Institute for Health and Care Excellence has published draft guidelines rejecting NHS funding for Bristol-Myers Squibb’s Opdivo as a treatment for locally advanced unresectable or metastatic urothelial carcinoma (mUC).

Patients with the condition have limited treatment options and are currently offered docetaxel, paclitaxel and best supportive care.

Opdivo (nivolumab) was approved by the European Commission in to treat adults with locally advanced unresectable or mUC after failure of prior platinum-containing therapy in June, making it the only immuno-oncology agent available in the region for this type of bladder cancer.

The decision came on the back of data from the Phase II CheckMate -275 trial, in which 20 percent of patients responded to treatment with Opdivo, a PD-1 immune checkpoint inhibitor, including 3 percent who experienced a complete response.

However, NICE argues that based on the available evidence, it is difficult to establish the magnitude of the clinical benefit for Opdivo compared with current clinical practice, given that the drug has not been compared with existing therapies in studies.

The committee concluded that the incremental cost effectiveness ratio for the drug would be between £67,205 and £86,030 per QALY gained (when compared with paclitaxel and docetaxel, respectively), and therefore agreed that the most plausible estimate of the ICER was £76,000 per QALY gained, far above what normally considers acceptable for end-of-life treatments.

Also, it said that Opdivo “does not appear to have the potential to be cost effective and is therefore not suitable for use within the Cancer Drugs Fund” in this setting.

Urothelial cancer occurs in the bladder or the ureter. It is the seventh most common cancer in the UK, with around 10,000 new diagnoses every year.


Drugs taking too long to be prescribed after NICE approval, pharma firms warn

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NHS managers and clinicians slow to begin process of ensuring newly approved drugs and medical devices are prescribed to patients, costing the NHS more in the long run, pharma companies allege.

Medicines approved for use in the NHS are taking too long to be prescribed to patients, major pharmaceutical firms have told a House of Lords committee.

Speaking at the House of Lords science and technology committee hearing into the government’s life sciences industrial strategy, Menelas Pangalos, executive vice-president of the Innovative Medicines and Early Development Biotech Unit at Astra Zeneca, said the UK was the most productive country in the world in scientific terms, but that this was not being translated into a commercial return.

The life sciences industrial strategy aims to ensure the long-term success of the UK’s life sciences industry, and it includes a chapter on improving collaboration between the industry and the NHS.

Pangalos told the committee that one of the biggest problems for pharmaceutical firms operating in the UK was getting drugs and medical devices adopted into practice in this country after they had been approved by the National Institute for Clinical and Healthcare Excellence (NICE).

“We need to find a way of working out how, when a drug is approved by NICE, it is used the next day,” he said.

“For a high-income country, we are one of the worst in the world at adopting approved drugs.”

Pangalos accepted that NHS budgets were tight, but warned that short-term decision-making was costing the NHS money in the long run.

“We need to create the room to see how we can save money over the next three years [by prescribing new drugs], as much as we need to save money over the next quarter,” he said.

Mark Campbell, senior manager of Randox Laboratories, which develops in vitro diagnostics, told the committee that his firm had experienced similar problems.

“Ninety-five per cent of our products are exported, but it is difficult when you are selling abroad and you stumble over the question of how your products are adopted in the UK,” he said.

Bryn Sage, chief executive of Inhealthcare, which makes digital home-monitoring products, told the committee that one of the problems was adoption decisions being made by such a wide range of people within the NHS.

“If we can get down to 44 or so accountable care organisations or STPs [sustainability and transformation partnerships] they may be much like the old strategic health authorities, but there should be someone in charge of the local health budget and someone in charge of the social care budget and it would mean we could sell [collectively] to 50 people rather than 500 people,” he said.

Andrew Dillon, NICE chief executive, told the committee he accepted that there could be delays in adoption of drugs and devices after they had received NICE approval.

He said NICE had already committed to providing guidance on cancer drugs within 90 days of their approval, and NHS England had agreed to fund all cancer drugs from the first day of approval.

NICE was consulting on extending its 90-day commitment to all medicines, he said.

Dillon also told the committee that NHS trusts had a statutory duty to fund medicines approved by NICE, although there was no statutory duty to fund approved medical devices or diagnostic agents.

This statutory duty did send a “powerful signal” to clinicians, but Dillon warned that it was no guarantee of implementation across the NHS.

“Then you need to rely on tens of thousands of decision-makers being aware of the guidance and then making those clinical decisions,” he said.


Cancer drug could cost NHS £4.7m per year of patient life, says NICE

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NICE wants to axe funding for Roche’s daily skin cancer pill, Erivedge (vismodegib), saying in final draft guidance that the NHS could spend almost £4.7 million on the drug to restore a year of good quality life to patients.

Erivedge is among the last in a backlog of 24 drugs that used to be reimbursed by the old Cancer Drugs Fund (CDF) – originally a ring-fenced scheme that paid for oncologymedicines rejected by NICE.

NICE was assessing Erivedge, which first became available via the CDF in 2013, as a treatment for adults with symptomatic basal cell carcinoma, or locally advanced basal cell carcinoma inappropriate for surgery or radiotherapy.

In a worst-case scenario where no survival benefit was assumed, Erivedge’s cost per Quality Adjusted Life Year (QALY) was a massive £4,694,943, NICE calculated.

Assuming that Erivedge gives a survival benefit, according to NICE it would cost the NHS just under £97,000 per QALY gained – well above its usual £30,000 threshold and likely too expensive even if end-of-life criteria had applied.

Cost per QALY gives an indication of the amount of NHS resources that would have to be diverted from other services to give patients an extra year of quality life.

At these costs, NICE was unable to recommend regular NHS funding for Erivedge, even though the manufacturer has offered a confidential discount.

NICE was unconvinced by the dossier of clinical evidence presented by Roche, and as the drug was not considered as meeting end-of-life criteria, the body did not have extra leeway when assessing cost-effectiveness.

There were also uncertainties about Erivedge’s impact on patients’ quality of life in the evidence submitted by Roche.

The CDF was last year reformed following huge overspends and pays for cancer drugs on an interim basis until NICE gathers further evidence to support their cost-effectiveness.

Meanwhile, all the drugs funded by the old scheme were reassessed, and in many cases, NICE has since recommended regular NHS funding after manufacturers agreed to cut prices.

Professor Carole Longson, director of the health technology evaluation centre at NICE, said: “Whilst it is disappointing to recommended that vismodegib be removed from the CDF, NICE must ensure that only medicines that are shown to be good value for money and clinically effective are approved for use on the NHS. As this drug was not cost effective it cannot be considered for use in the CDF.

“We acknowledge this will be disappointing for some patients.”

Roche said it is “extremely disappointed” in the decision but will not appeal because it said the current process will not change NICE’s mind, as its assessments are unsuited to rare and complex diseases as in the case.

The drug could be available to patients on a case-by-case basis should their doctors make special applications for funding, and NICE said it will work with health bodies across the UK to ensure all options are considered.

Richard Erwin, general manager at Roche Products Limited said:  “Roche is keen to work with NICE to find ways of developing its processes to ensure that they are suitable for medicines used in small patient populations where comparative clinical trials are not always possible and may in some cases be ethically challenging.”

Patients currently being treated with Erivedge can continue their treatment.

In a separate decision published today, NICE said it had in final draft guidance recommended regular NHS funding for Bayer’s Stivarga (regorafenib) for gastrointestinal stromal tumours. Stivarga will therefore come off the CDF.

While most drugs from the old CDF have been given regular NHS funding, NICE this summer rejected Ipsen’s Cometriq and Sanofi’s Caprelsa in first draft guidance.


NICE gives final draft guidance on two key cancer drugs

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NICE has announced it has published its final draft guidance for two cancer treatments, covering Bayer’s Stivarga (regorafenib) in the treatment of gastrointestinal stromal tumours (GIST), and Roche’s Erivedge (vismodegib) in the treatment of advanced basal cell carcinoma (BCC) that cannot be treated with surgery or radiotherapy.

Reorafenib is currently available on the Cancer Drugs Fund (CDF), but NICE’s latest recommendation advises that it should now be taken off the fund and made routinely available to select patients on the NHS as a therapy to treat GIST in situations where it has metastasized, cannot be addressed with surgery, or where no alternative treatments are appropriate.

The decision was based on data suggesting that the drug has the ability to extend life by over nine months compared to ‘best supportive care’, which manages symptoms but does not actively treat the disease. The price to be paid by the NHS for treatment has been negotiated as part of a confidential patient access scheme, and will be lower than the £3,744 per three-week treatment cycle noted on the drug’s list price.

Secondly, the appraisal committee at NICE has deemed that clinical benefits provided by vismodegib were unclear. This, combined with its high cost, has led NICE to the decision to recommend the removal the drug from the CDF due to its ineligibility, with final publication expected on 22 November. In this situation, treatments removed from the fund will be heralded by two month’s notice.

Both pieces of final guidance have been given to the relevant consultees, who are now free to appeal the decisions within.