OR WAIT 15 SECS
Leela Barham is a freelance health economist and policy expert. She has published in peer-reviewed journals and presented at national and international conferences. She has provided advice to the Department of Health and Social Care on policy on pricing of branded medicines to inform the negotiation of a successor to the UK’s Pharmaceutical Price Regulation Scheme (PPRS), the Voluntary Scheme for Branded Medicines Pricing and Access (VPAS), as well as worked with patient groups, the NHS, pharmaceutical companies and many others internationally on the economics of healthcare and pharmaceuticals. Contact Leela on firstname.lastname@example.org
NICE's David Haslam discusses the UK drug watchdog's new challenge in meeting expectations around what quantitative calculations of value mean to patient access today.
New leadership is finally settling in at what is arguably the world's most prominent arbiter of pharmaceuticals pricing and access—the UK's National Institute of Health and Care Excellence (NICE). Professor David Haslam, who began his career in academic medicine as a rural general practitioner (GP) in the National Health Service (NHS), assumed the position of NICE Chair in April 2013, succeeding the outspoken Sir Michael Rawlins, who, it can be said, single-handedly institutionalized the use of health technology assessment (HTA) to drive decisions on the use of drugs in medical practice, not just in the UK but in many other nations as well.
The last 18 months have put the modest, soft-spoken "physician's physician" under a great deal of public scrutiny. Haslam has managed controversial changes to the Pharmaceutical Price Regulation Scheme (PPRS), implemented in January, and is playing a prominent role in lengthy ongoing consultations with government, industry, and other stakeholders on a new value-based assessment (VBA) tool designed to clarify NICE guidance on NHS reimbursement for new medicines. Last month, Haslam helped vet the first NICE recommendation on an orphan drug, through a new highly specialized technology (HST) process to speed decision-making on access to patients in areas of high unmet medical need. Then there's the constant dull roar of dissent around NICE's approach to the assessment of cancer medicines, a moving target for standard cost-benefit metrics due to the complexity and undocumented promise of the many novel therapies now emerging from industry labs.
Photo: Gideon Hart
Other notable commitments taken up by Haslam include expansion of NICE's international activities, with new income generated from customized assessments and consultancy advice for other HTA agencies. A project in the Indian state of Kerala on maternal hospital care guidelines, support for HTA capacity building in Vietnam and implementation of clinical practice guidelines in Cyprus are just a few examples of this expanding presence beyond the UK.
In an interview with Pharm Exec, Haslam acknowledged he is often on the hot seat. "My job is to help the NHS get the best bang for the buck. This holds true for all of us who work here. We must recognize that every £ we put in to healthcare can only be spent once. And we want—and should expect—real benefit from that expenditure."
As a physician, Haslam is direct in stating that his overriding concern is the welfare of every patient affected by NICE decisions. His scope in defining that patient interest is broad, ranging from those who advocate through the media or serve as advisory committee experts to individuals with the condition that NICE is looking at—extending even to those who are silent because their particular condition may not benefit directly from access to a new medicine or device. "One of our key roles is to recognize how other health resources might be affected by the outcome of an individual technology appraisal. What else could that money be spent on? Who is going to miss out?"
Haslam laughs when asked if NICE will ever be able to escape the regular headlines in the UK press about "denying sick patients access to life-saving drugs." He says it is up to the media to decide to stop using headlines to provoke and emotionalize the debate, while noting that the media often publishes contradictory information simultaneously, which ends up confusing the public. "We often find that NICE is being criticized on the front page while inside the paper there is another story holding the NHS to account for not following NICE guidance," says Haslam. "I used to think you could not have your cake and eat it too, but apparently this works for some members of the press."
In a more serious tone, he acknowledges the important role of patient advocates who lobby and insist on asking the difficult questions. "There will always be pressure groups that focus on a specific condition and a given drug. They will make a lot of noise, and they are entitled to do that—it's exactly their job. But NICE and I have a responsibility to all those who are not making noise. When the strongest voice wins, the silent majority can lose out and so what we have to do is strike a balance between the two."
Haslam is conscious that Rawlins, who served as the founding chair of NICE for 14 years, from April 1999 to March 2013, is a tough act to follow. He doesn't shy away from the comparison, but points out that "trying to be another Mike Rawlins would just be impossible. He's unique. He's a world authority on many aspects of the issues relating to drugs and the use of drugs. I'd never ever pretend to fill his shoes. In fact, my job today is different because the organization itself has evolved, which is to be expected."
Haslam explains that NICE now has a very diverse mandate, which plays to his early strength as a GP, where he was used to treating every condition imaginable. NICE was originally set up in 1999 to tackle "postcode prescribing" of medicines, where there were geographic variations in use of medicines within the NHS. Today, the organization's tasks range from appraising new medicines to drafting clinical guidelines or formulating quality standards in social care.
Haslam says that when the NICE position came up, it became clear to him that NICE's job is much more than just technology appraisals. "NICE is an organization with an extraordinarily broad charter; we deal with orphan drugs at one end to palliative care in the home setting at the other. That breadth is where I thought my background as a GP generalist could help." Haslam explains that, "As a GP, you just have no idea what is coming next. The next person through the door could press you on any topic of medicine. The skill of being a GP is listening and working with patients to understand their concerns and expectations; what is going on in their lives that are causing problems. That applies to my role as NICE Chair, whether I am meeting government ministers, company executives, patient groups, journalists or anyone else. The first thing I have to do is to understand where they are coming from."
The biggest challenge Haslam knew he was going to face after starting in April 2013 was developing guidance for patients with multiple morbidities, which he notes covers most of the patient population. "Trying to work out the best way to address quality for individual patients is a tough task," but one he thinks NICE is up for. Tailoring evidence and analysis to the differences seen in real-life patients has been a long standing concern for the medical community, as there is really no such thing as an "average" patient. NICE has some leeway to cope with these differences, not only through extra numbers crunching that it might request from companies to explore how cost effectiveness differs according to patient characteristics, but also by developing "optimized" recommendations. These tend to recommend use for a subgroup of patients deemed most likely to benefit. Close to one in five of NICE's 532 technology appraisal recommendations completed through July 2014 have taken this "optimized" format.
Haslam’s Career Highlights
Haslam tells Pharm Exec that the review of statin drugs raised some unforeseen issues. NICE looking at statins isn't new. Its latest guidance, confirmed in July this year, changed the risk threshold from 20% to 10% for prescribing statins. The adjustment in clinical guidance has resulted in millions more NHS patients being eligible for statin treatment. It earned NICE another wringing in the headlines, this time on grounds of not saying no—the argument is that the NICE recommendation would promote increased access, perhaps too much. An open letter posted in June to Haslam from a group of senior physicians urged NICE to withdraw the guidance. Their concerns included hidden data, industry bias and conflicts of interest. The case has also led to questions as to who can, or should, provide expertise to NICE, especially when the parties are pharmaceutical companies producing the drugs.
Haslam is sticking by the statin guidance, though he admits it raises some "interesting questions" for the organization. Not least is who would provide expert views on real-world use of these products, at the desired point at or close to launch, if you can't include those involved in the trials that established the basis for product approval? He notes that NICE has updated its conflict of interest policy, with revisions tabled for review by the NICE Board at its September meeting. Not much has been changed: the focus is still on requirements to declare outside financial interests with few automatic exclusions. Expert advisors with the backgrounds that prompted concern in the statin guidance will still be invited to take part as long as they fully disclose their interests. NICE officials affirm that it has the discretion to invite an expert even where there is evidence of a potential conflict in those cases where he or she is the only source of advice available." Still, Haslam insists that NICE's conflict of interest policy will remain stringent and it is a priority for him to ensure it is fully enforced.
Haslam is also candid is admitting that the geographic discrepancies in access exemplified by postcode prescribing remains an issue, 15 years after it became a justification for the creation of his agency. "We're in a lot better place than we were, but there remains an issue of inconsistent implementation of NICE guidance across the system."
This is something that NICE is tackling through the NICE Implementation Collaborative. "We're working with academics, industry, patient groups and the NHS to figure out together why we haven't got the uptake that we want, and why the NHS can be slow to pick up NICE recommendations." This is occurring despite positive technology appraisals being supported by the legal requirement to fund access to these treatments, so that all patients who qualify get them. Haslam suggests that the Appraisals alone don't carry that legal mandate. "However, I would be uncomfortable if we made them mandatory. I want clinicians to use their wisdom and discretion with their patients along with our guidance."
He also points out that variation is, to a degree, inherent when the NHS is organized around clinical commissioning groups (CCGs), which hold budgets to prioritize and allocate care for geographically defined populations across England. He also acknowledges that "these are guidelines, not tramlines. They are intended to support clinicians and patients in their decisions which need to take into account issues like multi-morbidity and patient preferences." Generalists are also so busy that Haslam could not expect them to be on top of all of its guidelines. "That's why we are working to make guidelines as easy to find as possible, including tools that can be used during a consultation." But what he absolutely rejects is when specialists avoid applying any guidance in their specific area of expertise. "This won't wash with me. It is inexcusable not to have at least taken on board key messages that experts in the field have decided is optimal for their patients. NICE doesn't produce world-class research and practice-relevant guidelines for them to just sit on the shelf."
Cancer is the only therapy area to get it's own set of statistics for NICE's technology appraisal recommendations, which are posted for all to see on the NICE website. The cancer statistics updated to July 2014 are slightly at variance to the norm: 57% of recommendations are positive vs 62% for all recommendations (see chart). Of course, it's the "no's" that prove most controversial, and with a rejection rate of 33% of all cancer recommendations, it's a fact that this is more than twice the proportion compared to all other appraisals outside cancer. The numbers exist despite NICE's special consideration of the benefits of new medicines at the end of life, which can secure a "yes" when otherwise it would be "no." NICE's use of end-of- life criteria yielded 14 "yes" decisions on cancer drugs up to July 2014.
Comparing the total cancer technology appraisal decisions by NICE versus the agency’s total overall decisions during the period from March 2000 to July 31, 2014. Four recommendation categories are illustrated.
NICE has sharpened the spotlight on cancer drugs by publicly criticizing company pricing for many cancer medicines, stating that the high price tags give it little choice but to reject any positive guidance. For example, NICE recently delivered a negative assessment on the Roche drug Kadcyla even though it agreed the drug had clinical benefits for certain patients. It asked Roche to lower its price for Kadcyla.
Asked if he worries about the impact of the separately budgeted NHS Cancer Drugs Fund (CDF) on NICE, Haslam is careful to separate the political from the practical. The CDF is a ring fenced fund that pays for cancer medicines that either NICE has said no to, or hasn't yet provided an appraisal. It's a small pot, and only in August this year was it expanded from £200 million to £280 million a year. It only covers England, too, which leaves out NHS patients in Scotland and Wales.
"It's a tricky one. I respect the right of the government and politicians to address access issues that they think are important," says Haslam. "Cancer is an extraordinarily important topic but there are many other areas equally as important. A few months ago, I spoke to a group of patients with motor neuron disease. Someone in the audience, in a wheelchair, with tears running down his face, asked me 'what's so special about cancer?' Now, that's a painfully difficult question to answer. Yet that patient was right to ask it."
Haslam goes on to say "in the longer term, it will be helpful for the health services to find a way to bring together the NICE process and the CDF process. That's something we can accomplish, but it won't come overnight. There is momentum because the CDF is currently slated to end in March 2016."
Throughout the conversation at his London office, Haslam references back to the biopharmaceutical industry and the role it plays in making a difference to people's lives. He exhibits not a trace of smugness in claiming that he is wholly supportive of the innovative drug process. "We all need a vibrant, strong life sciences industry. My own brother died in his 30s from leukemia. But these days he wouldn't have died because of the medicines we now have that weren't available then."
What Does NICE Do?
Haslam doesn't share concerns raised by others about the potential negative impact on innovation from using generic comparators. He claims to be simply pragmatic on this score. "We do and will include generic comparators. We need to consider what is in regular use and the data that is available, and if that's a generic then it would be illogical not to use that in an appraisal." The same he says, applies to unlicensed products.
Haslam is also keen to point out how companies can work with NICE on the evidence needed to support the adoption of innovative medicines. This, he says, is not just about doing the requisite randomized controlled trial (RCT). "There is no tyranny behind our use of the RCT. We want the most appropriate evidence for what we're looking at. Through earlier scientific advice we can help industry develop the evidence that will support NICE making the best possible judgment about a new product. NICE is proactive in trying to involve industry at the very beginning of this process."
The early scientific advice service covering products at the Phase II stage of development is, Haslam says, "very popular." A quick stat check reveals that 34 companies have taken it up, and 17 of them have done so more than once. Haslam's not sure how many companies actually implement NICE advice: "I'd be intrigued if they didn't." The advice that NICE gives to a company isn't binding, nor is it determinative as to what NICE does itself. It's still early to determine its impact, and industry continues to express concern that NICE is able to change its mind about what it really needs by the time the actual appraisal is underway. The risk involves getting blindsided.
Halsam admits to being worried when companies choose to eschew submitting a new technology. That's happened 18 times to date. "I see this statistic as a lost opportunity. The NHS looks to us at NICE to provide them with guidance based on the best evidence available."
Soliris (eclulizumab) is the first example of NICE looking at an ultra-orphan medicine through its new HST process. Back in March, as the drug was going through the process, NICE asked for a "clarification" of the high cost of treatment. "High cost" in this case means around £340,000 per patient per year—although some experts dispute this price tag, it appears now to be the highest-priced drug ever. That translates to a cost for the NHS of £58 million in the first year, rising to £82 million after five years.
Picking up on this general theme, Haslam is pushing for more price transparency from industry. "Setting prices is a black box—actually, it's a form of art. I simply don't understand it. I'm not naïve, I recognize and understand the commercial sensitivities. But if we just understood a bit more about how pricing happens, that would be helpful to our committees." His concern must not be misinterpreted as advocating a role for NICE in pricing. "Setting prices is not for NICE. We come at price tangentially, i.e., we explore effectiveness and cost effectiveness once the price is set by the company. Everyone here is comfortable with that."
In the case of Soliris, NICE issued draft guidance in September recommending its use. But it hasn't let go of the pricing and affordability concerns, stating in its decision that NHS England and the company should consider what opportunities might exist to reduce the overall cost of Soliris to the NHS.
Haslam also remains unflappable when asked about his response to recent calls by John Emms, President at the Association of the British Pharmaceutical Industry (ABPI), for a "political reform" of the NICE charter and mandate. To the ABPI, reform starts with moving away from the cost per quality adjusted life year (QALY) that serves as the bedrock of NICE's methodological approach to cost effectiveness.
Paul Catchpole, value and access director at ABPI, adds to this by suggesting a new mandate may be needed in order for NICE to raise its "yes" rate for new innovative medicines. That has some resonance with the efforts of NICE's northern neighbor, the Scottish Medicines Consortium (SMC). After a major review on access to new medicines in Scotland during 2013, Alex Neil, Cabinet Secretary of State for Health and Wellbeing set out his expectation that changes to the SMC would result in substantially improved access to medicines for patients in Scotland. Observers and the industry see this as a political missive to have SMC say yes more often.
To that, Haslam just smiles, pointing out that although he'd need to check, he suspects "the same call has been coming in to the NICE postbox every month since the organization got its working papers."
When asked how NICE is changing in light of the 2014 PPRS accord with industry, Haslam emphasizes how the PPRS doesn't change NICE's basic cost-effectiveness threshold. That's contrary to the views of some companies. Roche, for example, has argued in response to the rejection of their £90,000 a year treatment for breast cancer, that the PPRS provides leeway that NICE isn't applying.
The complexity comes in because the 2014 pact includes a payback when the NHS branded medicines bill goes above an agreed rate—a rate that has been purposely kept flat for this year and next. Some £150 million has already gone from companies back to the Department of Health in two payments made under the scheme so far. It is likely that more paybacks will follow and flow back to the Department. Eventually that money will make it to the NHS, although no one quite knows exactly what it will be spent on.
Hence, the debate over the PPRS will likely continue. What is clear is that NICE will undertake responsibility for all elements of the assessment around a broader definition of value—what is now called value-based assessment (VBA), instead of value-based pricing (VBP). These changes entail introducing a burden of illness (BOI) and wider societal impact (WSI) metric, both still using the QALY but with some tweaks. NICE consulted with its stakeholders on these proposals from March through to June of this year.
Haslam won't be drawn into speculation about what VBA will actually mean; that's understandable when there are already concerns about ageism or sexism, and even both, in the proposed NICE approach to the concept. He cautions that NICE really did listen to the consultation responses on VBA it received through June, including comments from industry. "We had a lot of responses. There are many people interested in VBA. We're going to consider them all."
NICE published a Board paper updating its work on VBA and discussed it during its regular Board meeting last month. The paper does make clear that hardly anyone liked the proposals that NICE worked up, which drew on an expert working group involving experts from NICE, industry, academia and patient groups. Some 50 patient organizations, including cancer treatment advocates like Cancer52, also signed up to a public statement on VBA that expressed both disappointment and an ever optimistic perspective for a productive result.
What it seems likely to boil down to is this: no changes to the technology appraisal methodology, at least for the short term. Instead, NICE is suggesting "further consideration" not only of VBA and its technical details, but a "broader consideration of the way in which new treatments are developed, evaluated and supported for adoption in the NHS." The Board, when it met in September, suggested a "wider review of innovation," and is interested to hear what people make of three major suggestions:
» Creating an office for innovation within NICE to help companies navigate the path from development to adoption by the NHS.
» Formalizing agreement between NICE, NHS England (which distributes the money allocated to the NHS to CCGs as well as paying itself for specialized services, including some orphan and ultra-orphan medicines), and the Department of Health, on the NHS's willingness to pay for new medicines.
» More productive sharing of development issues and other associated risks between companies and the NHS.
With the backdrop of a general election looming for May 2015, progress will not be swift.
Haslam says that the European Medicines Agency (EMA) pilot on adaptive licensing has real potential. "It will help us sub-divide patient populations, exactly where real-world ways of generating evidence will matter." NICE, he says, "is involved in the discussions and will play our part" as the pilot progresses. It is early days for the program, though: the pilot was only announced in March this year, and so far EMA is only taking forward a handful of products that have been submitted for the pilot by companies.
Haslam is proud of NICE's evolving international engagement. When asked if NICE is trying to export the NICE model abroad, he responds "we're not evangelical, we simply act on the requests that come to us. We talk to the countries and we stress it's critical that they work out what their healthcare system is trying to achieve. That might be introducing universal healthcare or tackling inequalities. After that we can help them consider how best to achieve that, and to achieve the most bang for the buck." To do this, he says NICE promotes only its philosophy. "That means working with patients and the public, to be transparent and open whenever possible, and to establish ourselves as experts."
Haslam takes the same view when asked about NICE's relationship with EUnetHTA. EUnetHTA is a network of experts involved in doing HTA from the 28 member states of the European Union, supported by European Commission funds. He points out that "anything that ultimately reduces duplication could be beneficial. But I'm not sure we could or ever should aspire to a European-wide NICE. After all, there are differences among us that really matter, such as contrasting social values, medical practices and priorities."
Haslam is predictably positive about NICE's future. His demeanor remains upbeat even when asked about how NICE is prepared to deal with the difficulties of appraising stratified medicines, given the complex interplay of the diagnostics tools that accompany them. He admits the challenge, but offers the assurance that NICE will not stand still.
"Do we have it all worked out on how we can appraise innovations that come from discoveries in genomics? No, but we are working hard on getting the right fix," Haslam says. "What is in our favor is our objectives as an organization are very clear: help the NHS get the maximum benefit from the billions of pounds it spends, whatever the options are for treatment."
At the end of the interview, it is reminded again that Haslam was a GP—and he still thinks the same way as a country doctor might. His responses always reveal some of the curiosity he learned from experience about how vulnerable people approach the NHS for care and treatment. As the NICE remit grows broader, you can see how those generalist "people skills" are coming to the fore—and will be sorely in need.
Leela Barham is an independent health economist based in the UK. She can be reached at email@example.com.