Mesothelioma

Lord Freyberg Excerpts

Thursday 27th October 2016 Grand Committee

[Lord Freyberg (CB)]

My Lords, I thank the noble Lord, Lord Wills, for securing this debate and giving us an opportunity to discuss this subject once again.

I shall focus my remarks today on how we might improve mesothelioma surgery in the NHS. It is a subject that rarely gets discussed, but one that deserves much more attention than it gets at present. I was delighted that the noble Baroness, Lady Couttie, was able today to highlight some of the options available.

When my sister Annabel was diagnosed with mesothelioma a couple of years ago, one of the treatments available to her was radical surgery. This meant removing her pleura, the lining surrounding each of her lungs. Finding a surgeon with the right experience was not a straightforward process and relied entirely upon a Rolodex network of surgeons that her oncologist had built up over many years, often scattered around the country. Eventually, she found someone to evaluate her, but it took a long time to arrange and the procedure proposed was very risky, which was due in part to the fact that her tumour had grown so rapidly since her original diagnosis. On top of that, the surgeon, although very experienced, had not performed the procedure very often and lacked the familiarity of approach that specialisation usually provides. Given its radical nature and the need for complete tumour removal, should not surgical resection be concentrated at one centre of excellence, where patients can receive immediate attention, new techniques can be researched and surgeons can benefit from training and others’ experience? I am sure that patients will be willing to travel as far as needed to be in the hands of super-specialists.

Given the highly specialised procedure of removing pleura, what research is currently being carried out on resection methods? How does the NHS plan to optimise its approach to such surgery? Does it, for example, appear in the National Institutes of Health research plan? If not, why not? Again, there is huge scope for improvement here.

With regard to new drugs, what research is currently taking place on the impact of preoperative non-steroidal anti-inflammatory agents, given their success in other forms of cancer surgery? This should be another research priority for the NIHR, especially given the chronic inflammation component of mesothelioma. The synergies are such that we ought to be applying the benefits of such cancer research wherever possible. This is a cheap intervention, given that the drugs are generic.

All these issues point to the need for a specialist surgical registry and surgical outcome transparency in mesothelioma. Even transparency on the basics of annual volume and 30-day mortality by surgeon, centre and surgical approach would allow the supervising oncologists to find experienced surgeons in a timely manner. It will also allow for continuous surgical method improvement and best-practice dissemination. This holds true not only in mesothelioma but in less common and rare cancers requiring radical high-risk surgery. These cancer surgical registries should be a priority for the NIHR and NHS England. We need clarity about which body is responsible for their funding, given that they span both quality control and research. I hope that the Minister will encourage the bodies responsible to outline how they plan to drive and develop surgical registries and associated research in these cancers.

Access to Medical Treatments (Innovation) Bill

Lord Freyberg Excerpts

Friday 26th February 2016 Lords Chamber

[Lord Freyberg (CB)]

My Lords, I, too, am delighted to support the Bill. I speak today, as many noble Lords do, as one touched by the tragedy of cancer. As some noble Lords may know, my sister died two years of mesothelioma. Recent data from the Office for National Statistics show that 43% of cancers are less common cancers such as mesothelioma. While each is small, collectively they account for well over half of cancer deaths. There is insufficient commercial incentive globally for the current innovation processes to bring new hope to sufferers of these terrible diseases. We can see this in the rate of improvement in annual mortality ratios, which are the number of deaths linked to a cancer divided by the number of incident cancers. In the top five cancers, mortality ratios have improved 12% since 1999, from 49% to 37%. In the less common cancers the improvement was only 4%, and today’s mortality ratio is a shocking 56%, 19% worse than the 37% found in common cancers. That is three times less innovation in less common cancer.

So where have the modern precision drugs been launched? They have been launched for common cancer, of course. What is that? It is economics. At $75,000 per patient, cancer clinical trials are immensely expensive. It can cost billions to bring a drug to market. Where are rational economic agents going to place their research bets? They will do so in the big markets of common cancer, not the small, such as mesothelioma.

What is so unfortunate is that less common cancer has the same underlying genetic causes as common cancer. Modern precision drugs developed for common cancer often, but not always, work in these rarer diseases, but the costs of trials and the challenge of finding patients in rare disease mean that little development happens. That does not matter much in the US, the largest market in the world. There, a physician can prescribe off-label. There is no rationing watchdog like NICE breathing down his or her neck. US insurers will generally pay for the drug, with very limited data, such as a small case series in that cancer. As a result, the largest market in the world has extensive off-label use and does not require costly trials in rarer cancers. By implication, most of the economic incentive for formal label expansion vanishes. Pharma can get revenue without much R&D cost. Sadly, the research potential of this off-label use is not captured in the US, as its balkanised healthcare system does not capture the outcome data needed to close the loop and to discover what works for whom.

It is in this global context that we must evaluate this Bill. In particular, concerns about the Bill overriding UK due regulatory process ignore these economic realities. This is not the 19th century; there is no sea of pink on the maps. The regulatory and reimbursement process that matters globally for the pharma industry is the US, not the UK. We are a paltry 3% of the global market; it is 40%. Also, the US has a system that allows promiscuous off-label use. We must deal with the consequences of those global incentives and not be distracted by due process, as the noble Lord, Lord Ryder, stated.

Let us explore this global context further. As the noble Lord, Lord Saatchi, mentioned, US Vice-President Joe Biden is leading Obama’s $1 billion moonshot on cancer, after his son died of a rare brain cancer. A key part of that initiative looks set to be a database similar to that proposed by this Bill, implemented in willing but small US integrated care systems such as the Veterans Association. These databases have a name: stratified outcome registries. They are large-scale, real-world clinical databases, but upgraded for the 21st century with molecular diagnostic information, treatment outcomes and electronic consents. They capture not only what works for whom but, as importantly, what does not work. They close the learning loop.

I have consulted the supporters of the Bill and will be looking to see that it is appropriately amended—or not, depending on how we come to it in the time limit—to this effect in Committee. That is in line with the recent input from the Association of the British Pharmaceutical Industry on the importance of capturing both the good and the bad in such a database.

I also commend to the House the work that is being done by a small and innovative US not-for-profit, Cancer Commons, in helping to design such registries. In the US, it pioneers the application of these registries for optimising the use of existing drugs in common cancer and extending their use into less common cancer. It points out that such databases have a number of other benefits. They can discover which patients will not respond to costly treatment, saving those patients side-effects for no gain and saving the system money.

As an example, my sister had a molecular test that showed that cisplatin would not work for her cancer and would be more toxic for her than for most. As it is the NHS’s standard cancer treatment for the disease, she was given it. The toxicity occurred as predicted. She suffered horrendously and became ineligible for trial. The NHS faced significant costs in managing those unnecessary side-effects and complications. My sister might have lived a few months longer but for the side-effects.

Another benefit is that these databases have enough molecular information for scientists to hypothesise why a drug worked or did not work and so pump-prime basic research. Where we cannot explain the response, we can feed those exceptional patients to Genomics England, which will make that superb basic research engine more efficient. Finally, over time, the database would generate the information to derisk formal trials in less common disease. That will make such trials more economically attractive to industry and so change drug availability globally.

What may not be known to the House is that the UK is well placed to lead globally on developing these databases. In particular, we have a secret weapon in the National Cancer Intelligence Network registry in England. This covers 280,000 new cancer patients a year and today captures classical presentation, treatment and outcome data and small amounts of molecular data. The best US outcomes registry today covers fewer than 30,000 patients a year.

That volume of patients with clinical data gives us huge power globally. It is the largest in the world by a factor of 10, housed in the country that led the human genome initiative and with an enviable clinical research tradition. We should aim to use it to recraft the NHS to be the workshop for the world in precision oncology. This would win back a significant share of pharma’s global R&D spend, create a huge number of high-value precision medicine research jobs, and have a positive impact on investment flows into the UK. In particular, if we deployed low-cost generic panel-based cancer molecular diagnostics proactively into the NHS and ahead of approved drugs, pharma would supply late-stage research drugs in less common cancer. It would do this because the clinical data generated would both encourage off-label use in the US and give it future expansion options.

The evidence for this can be seen in France, where the Institut National du Cancer has been driving a national molecular pathology programme for over a decade. It is the preferred European partner for large pharma like Pfizer for late-stage clinical trials in precision oncology. That investment also created equality of access to modern molecular diagnostic technologies and prevented a testing postcode lottery. Today in the UK, we have an appalling postcode lottery in molecular testing, as recently highlighted by the Independent Cancer Taskforce and the NHS Atlas of Variation in Healthcare. We need the political will to change how we fund molecular diagnostics in the NHS to alter this. France drove the adoption of such tests by top-slicing the hospital care activity budgets to create a dedicated pool of money for a national testing programme and taking on entrenched vested interests to drive reform. We need to be similarly brave and creative if we are to achieve this here but it will save money and lives.

If we upgraded NCIN to being a stratified registry through the investment in a national molecular pathology service, I am confident that quickly some, but not all, UK patients would also live longer as a result of the increased access to innovative drugs. Over time we will also close some, but not all, of the yawning gap in mortality burden in the less common cancers, and we would have an intelligence system that could manage the risks of real-world innovation.

If such a system had existed when my sister had been ill, it might have helped her. Half of us will get cancer—it might well help you. In short, we can do well as a nation by doing good for the world. We can make the UK the preferred destination for the US drug companies for their clinical development, but only if we reshape the NHS to be a cradle for the sorts of innovation supported by the Bill, not a barrier. Let us use the global drug development system and its perverse incentives to our national advantage. Let us support the Bill and its database of innovation and work together on the many important details that may need ironing out in Committee.

Health: Cancer

Lord Freyberg Excerpts

Wednesday 20th January 2016 Lords Chamber

[Lord Freyberg (CB)]

My Lords, I begin my speech with a startling fact: rare cancers accounted for 43% of cases in 2010, but 59% of cancer deaths. Let me repeat that: these less common cancers affect roughly four in 10 of new patients, but make up six in 10 of deaths. If we want to improve survival overall we have to improve our performance in these cancers, and our performance in caring for them is poor relative to international peers. Broadly speaking, in every case there is a 5% to 15% gap in the UK’s one year performance. In stark numbers, we kill one patient more for every 10 we treat. This cannot go on.

So what can we do to improve care in these cancers? First, we should publish risk-adjusted hospital survival by cancer so that patients have informed choice. These do not need to be put into the NHS dashboard if that will delay things. Patient advocacy groups can pick up the data and take them to their constituents.

Secondly, we should measure other important care quality outcomes, such as incontinence in prostate cancer. To give noble Lords a sense of the power of measurement, Germany recently introduced metrics in incontinence and impotence after prostatectomy. On average, about 50% of German patients are left incontinent, except in Hamburg, where the Martini-Klinik has been tracking its outcomes to drive internal performance improvements. Its rates are 6.5%—in other words, a national average of one in two men in diapers for the rest of their lives, versus one in 20.

Thirdly, we should streamline diagnosis and better connect primary and secondary care. The Government should be commended for putting one-year survival rates and emergency presentation data into the CCG dashboards, and these will drive local behaviours in this area.

Fourthly, we should centralise more services, especially specialist surgery. As an example, my sister’s cancer was in the chest cavity. Getting access for such thoracic surgery is highly complex and risky. General surgeons doing these sorts of procedures get worse outcomes than those who do them more often. It is like playing the piano; the more you practise, the better you get, yet we run shy of the necessary service reconfigurations to achieve this; and, without the data on hospital performance, one can see why. Patients can judge only convenience.

Fifthly, we should introduce national molecular testing for those cancers where there is no service incumbency, such as cancers of the upper digestive system or of the female reproductive system. We should use that patient volume to catalyse precision medicine trials in these diseases. They share the same genetic mutations as common cancer, and so, if pharma can recruit to trial, they will prove whether their drugs for common cancers work for these less common ones.

Sixthly, we must continue to collect rich clinical data on all patients with cancer out of routine care. This is essential in the emerging era of personalised molecular medicine. England has at the moment the largest and best cancer registration data collection service anywhere in the world. It is this rich clinical data linked to the molecular and genomic analysis that will allow us to understand both rare and common types of cancer. However, if we allow large numbers of individuals to opt out of the registries, then our hopes for improving care quality and finding treatments and cures for rare cancers will be lost for ever.

While some of these measures will cost money, some are cost-free. Public Health England, in the form of the National Cancer Intelligence Network, has hospital survival data, but we just do not publish them on. The Government have made a commitment to open data. This is an area where data can save lives. We must unlock Public Health England’s vaults and give the information to patients and doctors.

National Health Service

Lord Freyberg Excerpts

Thursday 14th January 2016 Lords Chamber

[Lord Freyberg (CB)]

My Lords, this debate is about present and future demand and how we best manage it. In doing so, we need to include all rare disease, not just the big killers. Individual rare diseases may not kill many, but collectively they are a significant part of the disease burden.

Mesothelioma is such a disease. In the recent mesothelioma debate, the Government confirmed that 60,000 are expected to die from that terrible disease over the next 10 years. An international comparison by the Eurocare group shows that the UK survival rate at one year is 36%. Sweden’s is 46%. In other words, one in 10 patients more dies here than in Sweden, or 6,000 lives over the next 10 years. The disease is identical and the treatments identical. This is therefore a matter of care quality management.

We see this pattern across cancer. The British Journal of Cancer published the latest international performance assessment. Here is a sample of the one-year survival rates for 2005 to 2009. In lung: Sweden 41%, England 31%. In colon: Sweden 82%, England 73%. In ovarian, Sweden 79%, England 64%. This sounds remarkably like the England football team’s latest performance against Sweden. Perhaps, as in football, we should turn to Sweden for management advice.

Sweden has driven improvements in its service not by chucking more money at the problem but in the way it manages the service. Hospital quality is published at a granular level, not some meaningless general level. Patients with a specific disease know which hospitals to avoid. Some of your Lordships will recall the Colchester cancer scandal. What did not come out in the media at the time is that the East of England Cancer Registry foresaw such an issue many years before in research showing that smaller centres had worse outcomes than larger ones. They may still do, but who is to know without the data?

Yesterday I tabled a number of Written Questions for the Minister on the data that the Minister already has in the National Cancer Intelligence Network in Public Health England, which could help patients to get better care if it was published, such as cancer-specific hospital performance data. I am sure that the Minister would agree that these are important issues, and that the reasons they are not being published should be investigated. Once these investigations have happened, will the Minister agree to meet me—I would be grateful if the Minister could reply on this point in his wind-up—to see how these results could be put into the public domain? I believe that these figures are an important component in seeing improvements in cancer care.

Mesothelioma (Amendment) Bill [HL]

Lord Freyberg Excerpts

Friday 20th November 2015 Lords Chamber

[Lord Freyberg (CB)]

My Lords, I support the Bill and I, too, congratulate the noble Lord, Lord Alton, on bringing this issue back to Parliament following its narrow defeat in this House in 2013.

Like the noble Lord, Lord McNally, my interest in this subject is personal. Just over three years ago, in June 2012, my sister, Annabel Freyberg, a journalist, was diagnosed with mesothelioma. Her diagnosis followed one month after the death of her nine year-old daughter, Blossom, from a particularly virulent cancer, neuroblastoma. The process of her diagnosis was long delayed as the symptoms of her severe lung problems were initially put down to pneumonia and stress. Over the next 18 months there followed a succession of treatments: a course of chemotherapy; attempts to join various drugs trials; and introductions to different specialists who might have been able to operate on the tumour, but, sadly, by then it had progressed too far for this to be possible. On 8 December 2013 she died, aged 52, leaving behind her husband, Andrew, and her 13 year-old son, Otto.

Statistically, Annabel is an anomaly—one of only 415 women out of 2,538 people who died of the disease in 2013. Most people with mesothelioma are men in their late 70s who worked in areas such as the building industry and were exposed to asbestos. It is rare for a woman in her early 50s to have the disease. To this day we still have no idea where and when she came into contact with asbestos. However, for many women and their children, the link is all too clear and especially cruel. As the noble Lord, Lord McNally, and others have said, they are the wives exposed to deadly asbestos fibres while washing their husband’s clothes, or children exposed to asbestos after greeting their fathers from work.

One of the troubling aspects of Annabel’s illness, which was highlighted by successive visits to oncologists, was how little research there was into mesothelioma, as with most of the rarer cancers. It is surprising that although the UK has the highest rate of the disease in the world, relatively little is spent on research in the UK, measured against other cancers of comparable mortality. As the noble Lord, Lord Alton, and others have already mentioned, the British Lung Foundation estimates that in 2014 only £860,000 was invested in mesothelioma research by its partners, compared with £9.9 million for skin cancer. The consequence of this was that many of the trials available to Annabel took place outside the UK.

However, the story of consultant anaesthetist Andrew Lawson, who survived seven years with mesothelioma, shows that it does not have to be this way. Given a year to live, he investigated the evidence and took advice from colleagues from all round the world. There followed three operations and six different chemotherapy courses. He signed up for clinical trial gene therapy treatments in Philadelphia and dendritic cell vaccine treatment in Holland. At his own instigation, he was the first mesothelioma patient in the country to have regular treatment with intravenous bisphosphonate after promising results on mice in Western Australia. Of course, none of these is readily available on the NHS and, indeed, most patients are simply not told about such trials or know of such basic research.

However, it demonstrates the need to rethink how we carry out our research. The present system of trials is far too slow, too expensive and unsuited for rarer cancers such as mesothelioma. The fastest way to save lives is to see if the drugs for common cancers work on the rarer ones as well, given the shared mechanism of disease across cancer. This is off-label research and until we fix the issue of liability, as advocated by the noble Lord, Lord Saatchi, we will continue to send thousands, like my sister, to an early grave.

One promising aspect of my sister’s treatment, however, was an early use of broad-panel molecular diagnostics. There was no facility in the UK at the time to do this and so her tumour sample was sent to America, where her DNA was genotyped. The results were very revealing but, in her case, proved too late for her to benefit. She had started a course of cisplatin, the standard cancer treatment for the disease, to which she had an adverse reaction. The test results, which we received five months later, suggested that that would happen as she was not suited to the drug and should not have been given it.

I was pleased to read that in Cancer Research’s strategy paper for 2015-20, Achieving World-Class Cancer Outcomes, a key recommendation is the use of such diagnostics to improve cancer treatment. I hope this will be facilitated, for without it we will give many more patients like my sister expensive, toxic and ultimately futile therapies. More importantly, I hope that the data from such national molecular tests can be gathered into SACT, the national database in Oxford which tracks cancer outcomes. This will only improve survival rates and provide, if properly managed, a powerful resource for clinical research.

I warmly support the Bill and hope that it will have an opportunity to be enacted.