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A change of Health Secretary (not before time) and a fresh set of messages about reducing the pandemic constraints on life should be welcome developments. The fact they aren’t deserves careful examination.

This pandemic has taken many twists and turns, usually with government unprepared (or at best under-prepared) for the development, and often responding far too late to the data which they claimed was driving their decision-making. The unwillingness to empower local action and to centralise efforts failed, a signal which seems to be ignored.

We now have the situation where infections are climbing once again, with a doubling time of around a week, most of those infected are young people, and government decisions seem to be based on the fact that vaccination response is so good among adults, especially in the older generations, that normality can return. Whatever that normality turns out to be.

There are unknowns. What is going to happen to the hospital admission rate as infections rise? That is already testing some NHS Trusts. The issue of deaths is disregarded, it seems they are going to remain low, but no-one can be certain. A rising incidence in Long-Covid among younger people is a threat that is brushed aside. Potential mass-spreader events are now permitted – acceptable risk?  The UK’s border policy seems more robust than it was, but inaction allowed the Delta variant to be introduced from India and to take hold. Could that happen again?

The dominant political stance is that as so few people (as a percentage of the population) now get seriously affected and vaccination has reduced that to a lowest ever position, we can let go of all constraints on life. The economic impact of the first waves must be overcome and our ‘freedoms’ returned, to be sacredly preserved.

I am worried.

First, because the NHS has been destroyed. It is still there in name but you cannot see a GP (you may get a phone call), your highest risk for getting infected is to visit a hospital, NHS staff are exhausted and stressed, the backlog of unmet need is at its highest level ever, and political shenanigans resulting from the pandemic have tainted a valued ethic.

Second, consequent deaths are a growing issue. Cancer death rates will rise because of delayed diagnosis and treatment, similarly for other conditions. Disability rates in the population will rise because of untreated conditions, or conditions which become too difficult to treat.

Third, inaction on social care means that the NHS will become an old people’s home. It is too much like one already. Government promises to address social care have sounded hollow for a long time but now the growth in the elderly population is about to burst as the post-war baby-boom generation approach 80.

These are structural issues which need a combination of leadership, strong values, integrity, political collaboration, imagination and resources – all of which seem to be in short supply.

But consider that the pandemic is not over yet. The impact on young people is a great concern but perhaps the greater issue is the unknown behaviour of the virus as it mutates. All these other issues could be a minor distraction if a variant emerges which escapes the effect of vaccines. I can respect the cautious optimism of the scientists that they can address variants. Their caution is common sense, qualities absent from politics.

At its worst we could be heading into a healthcare crisis beyond imagination. If, somehow, we can grasp the challenges and start to have good luck with the virus, the damage can be addressed.  It’s a set of fine balances but personally I have no confidence that we can be anything other than blown through the storm by winds beyond our control.

I had the privilege and the pleasure earlier this week of chairing a patient group meeting. You might think I have done a lot of that so why should it be so special this time. It is true, I have chaired and been part of patient groups quite frequently over more than 20 years but this one was special for a number of reasons.

First, it was of course a Zoom meeting – a screen full of unfamiliar faces, intriguing backgrounds, challenges with mute buttons, and some variable framing.

Secondly all those attending had been treated for a retroperitoneal sarcoma (RPS). This is where a sarcoma occurs inside the peritoneum. These tumours are rare, accounting for less than 300 cases a year in the UK. They can become extremely large, rarely causing pain until they put pressure on organs, thus often being diagnosed late. The main treatment is surgery which can be extensive, patients can lose organs compromised by the tumour. During the last ten years the surgeons around the world who specialise in this demanding surgery have come together as an international working group (TARPSWG), shared data, and have agreed that radical approaches are needed to deliver the best outcomes for patients.

I have only ever previously met one or two at a time of RPS patients. At this meeting there were 15, some initially treated more than ten years ago, a couple only treated last year and still getting to grips with their recovery.

And third, most of these patients had been treated by one surgeon – a member of the specialist surgical team based at the QEII Hospital in Birmingham. He was in the meeting too, along with members of his team and a research statistician.

This team are leading the development of a clinical study about follow-up. The TARPSWG group has recognised that there are no standards and it is impossible to identify the most effective approach to follow-up currently used around the world. For some patients it is probably unnecessarily intense, others may benefit from greater intensity – no-one is sure. Some patients have higher grade tumours (more aggressive), others are low-grade, and there are also variations in tumour histology.  Hence the work on the study.

The purpose of the meeting was to explain the background to the study, what is currently being planned, to get patient responses to some specific questions the study team have, and to see what issues the patient group raise and want to discuss.

Even though all of them were RPS patients the individual experiences were extremely varied. One person had had a primary tumour which weighed 35lbs (15.8kg), another described theirs as “large as a mango”. Several had serious organ loss – kidneys, spleen and other organs. A few had had recurrences and were in continuing treatment or active surveillance. It was a genuine cross section of lived patient experience. A couple shared their screen with a partner, both of whom also contributed valuable comments and ideas.

It was a lively meeting and the input from those assembled on screen was truly remarkable. I assured them at the outset that no question was ‘silly’, just give out whatever came to mind. Inevitably there were very individual issues expressed and we had to ensure that some of these were side-lined to become a personal call from the surgeon. But the readiness to understand concepts which are not in general public debate (eg randomisation, timing of questionnaires) and to constructively consider what intensive and less intensive follow-up actually meant for patients, was tremendous. I was especially encouraged by the willingness to grasp what ‘quality of life’ meant and how researchers go about assessing it.

I have always said, never under-estimate what an involved group of patients can bring to a study, and it was as true here as it ever was. The range of responses and issues raised will provide an invaluable input to the study team as they develop the idea further.

A truly special afternoon and I have to thank all those who took part for the privilege of meeting them and also the Birmingham team for the invitation to take part.

If you have read this blog regularly you will know that I am not entirely comfortable with what is going on in cancer clinical research at the moment. I can appreciate innovation and recognise that scientific developments which may benefit patients need to be tested in clinical trials. However, stresses are showing.

When I started learning about cancer research, things were fairly simple. That wonderful teacher Derek Stewart defined patient involvement as learning to balance benefits and burdens. We needed to listen, question, challenge when appropriate, and when we had experience or information which was relevant, to make our voice heard, politely. These are fine principles and experienced patient advocates everywhere recognise them.

Targeted drug therapies have been challenging established models of research. The pinnacle of a drug’s journey to market used to be a Phase 3 Randomised Controlled Trial (RCT). Regulatory approval followed trial success and started the process of getting a new treatment into standard clinical practice. When involved with RCTs the concept of equipoise was an important one for us to understand; learning about endpoints, outcome measures, inclusion and exclusion criteria, side effects and their management was all do-able provided you were prepared to learn. Then you learned about ethics, you got into discussion about placebos, early stopping rules, systematic reviews – the list grew and grew. There were plenty of people happy to help with all the learning.

When you needed to look at research in a more strategic manner, as happens when you work on a programme of research or developing clinical guidance, you find that there are new issues. Questions can be harder to define and not always asked or answered in the systematic reviews. You need to ask questions in order to discover the real questions you need to ask. You find the professionals take certain knowledge for granted and may not see why it should be questioned.

So what is it which worries me about clinical cancer research today?

Results from Phase 2 studies now unlock registration leading to NICE opening up interim approval and funding for NHS use. The Cancer Drugs Fund (CDF), soon to be extended as an Innovative Medicines Fund, enables drugs which have not been tested in an RCT to be evaluated within standard clinical practice. Evidence on that experience can open up full regulatory approval. This journey is replacing the RCT.

Perhaps the most challenging current research is the work on genetically modifying T-cells, the body’s natural immunotherapy. There has been a lot of publicity for the technique, which has benefited a few patients, although the long-term benefits are completely unknown. CAR T-cell, as it is known, is a complex technology, very well explained on the NHS website if you need to know more. It is also very expensive.

The NHS centres conducting the CAR T-cell studies on diffuse large B-cell lymphoma (DLBCL), have been charged by NICE with reporting on their work by March 2021. An initial report was presented at the recent ASH Convention in Florida and the results so far are disappointing. Sadly trials in a lot of targeted drugs and immunotherapies are disappointing.

This is where questioning comes in. This is the pinnacle of personalised medicine. These patients have advanced cancer which is untreatable with standard therapies. An assessment of how long patients survive and what other treatments achieve are questions which need an answer, together with a proper appraisal of quality-of-life. There are further questions about biomarkers which could predict response, predict side effect problems, even perhaps predict a cure. All these are questions which the scientists involved know about and will try to answer without an RCT.

But there are bigger questions. Should these therapies be tested at an earlier stage of disease? Would similar sums spent on maintenance therapies which hold relapse at bay deliver better and more patient-centred care? Never mind value-for-money. Are we being dazzled by our own cleverness?

We have seen that with these new treatments a truly prospective RCT may not be feasible. We need a new rigour in our system which can unlock patient benefit. I believe the answer lies in the NHS itself. We have 150 cancer hospitals using the same data standards for recording cancer clinical performance. We must engage the real world of clinical practice more widely in the research challenge. There are many cancer treatments where research in the real clinical world could add value for both patients and the NHS. We can gather data in a structured manner on every new treatment. Consent for treatment allows your data to be used for research.

This is an environment where we can go further. We could construct prospective studies, without relaxing our research consent practices. We should be looking at the sequencing of new drugs where more than one is available for any condition, accruing patients into the studies from any hospital. We should be looking at studies of combination therapy, new-with-new and new-with-old. We should be looking at the ‘minimum effective dose’ of a drug rather than blindly accepting (as we do) the developer’s recommendation based on ‘maximum tolerated dose’. We could be looking at studies using known effective drugs earlier in the course of disease, or as maintenance therapies when there is no disease present. We could look at new indications for approved drugs. We should build studies like these with patient involvement, questions defined by patients should be answered. Patient Reported Outcomes should be at least co-primary endpoints, we might even get ‘patient preference’ accepted as a standard outcome.

Industry has no real interest in running studies of this kind. Their interest is commercially driven despite high-sounding words about better patient outcomes. Their real world studies that lead to converting interim drug approval into full and funded NHS approval are run in their commercial interest. Their studies receive funding through the Cancer Drugs Fund, guaranteeing the manufacturer an income, but there is no automatic funding for real world NHS research with a patient-led focus. That funding has to be found. As therapies are already funded through CDF or NICE approval treatment would not be a study cost. A study will all be about prospectively gathering and analysing data. The NHS is capable of doing it and is in the NHS’s interest to get such results.

A focus on high technology in cancer research is important but it must not be the primary focus. It is great for creating headlines and makes wonderful TV but we have seen that very few patients benefit and costs are phenomenal. I am not saying we should not do it but I am saying that we are failing to do the other things which the NHS is uniquely capable of delivering. Cancer research is doing a dis-service to everyone, not just to cancer patients, if it does not shout about this challenge.

We need routine research within clinical practice, we need real world evidence, we need it to be driven by patient reported outcomes. Given the growing cost of drugs I believe that every penny invested in such research could be returned in value to the NHS.

Five events, two months, some important messages and valuable feedback. It has been a busy autumn this year. Preparing a presentation takes time so these trips have taken out a huge chunk of time, although to be fair two of these events did not involve a presentation. In one case I chaired a panel and another involved a dinner and a Board meeting. Each event also gave opportunities to meet and discuss matters with other patient advocates in both informal and more public settings.

Its worth looking at each of these events and seeing if we can draw some conclusions. Its also worth noting that a patient is often included in a programme a bit reluctantly so ensuring that what we say is well grounded in evidence that cannot be ignored is an important step to take. The character of the organisation running the event is therefore also an important background consideration.

The first of the five meetings was the ECCO Cancer Summit. ECCO has evolved as an organisation developing a clearer focus than hitherto on influencing policy within Europe. Within its structure it has a Patient Advisory Committee which makes significant contribution to the work which ECCO undertakes. The PAC is chaired by Ian Banks, a patient from Northern Ireland, and includes in its membership a varied and experienced group of advocates from all across Europe. The Cancer Summit was created to focus on some key issues and to agree how they should be represented. It also gave the chance to debate some issues at an earlier stage in their development, when clarity about what is involved is necessary. Patient integration in the Summit was excellent.

I co-chaired one of these debates with Dr Denis Lacombe of EORTC. The issue is the growth of short-term clinical studies resulting in regulatory approval and the loss of the scientific rigour which comes from Phase 3 Randomised Controlled Trials and long-term studies post-regulatory approval. The demand for evidence of value from Health Technology Appraisal (HTA) agencies which approve funding for national healthcare systems, and from patients wanting better quality information, creates a need for evidence from routine clinical practice (Real World Evidence – RWE) in the absence of prospective evidence. There are, as yet, no structures of any kind to support such studies, which take place ad hoc, have no consistent standards, are open to bias and dis-information.

What did our debate conclude? There is a need for industry, academic and regulatory organisations to work together to set RWE standards and create a route for accountability. EORTC’s Manifesto on Treatment Optimisation provides a strong foundation for a such collaboration. The ball is now in ECCO’s court to move this forward.

Then came ESMO, an event of such scale that describing it is almost impossible. Close to 30,000 delegates, up to 12 parallel conference streams, the largest cancer focussed exhibition in Europe, altogether astonishing. I followed streams on sarcoma, quality of life and PROs, patient involvement in clinical care and research, survivorship and trials methodology. Quite difficult prioritisng because there were many schedule clashes.

I spoke in a session on ‘Surviving a Cancer Diagnosis with a Good QoL’. Its a very open topic and the speakers covered a wide range of issues. A highlight was the work of Isabelle Lebrocquy from the Netherlands on cancer and employment. She has created a charity, oPuce, which helps get people with cancer being refused employment because of a cancer diagnosis, into jobs that they want.

The sessions on sarcoma had many important revelations – treatment of GIST, mifamurtide 10 years on, sorafenib for Desmoid tumours, radiation sarcomas and developments in precision medicine for sarcoma. The Patient Involvement session in the Nursing stream was very disappointing, poor quality information, nothing new or exciting, although there was an excellent case study from the Royal Marsden. The Patient Track in the programme included an excellent debate, in memory of Hans Keulen, about going the extra distance to extend life when terminal. Kathy Oliver chaired this superbly. Other standouts included a talk on Survivorship from Australia, and discussion on Fatigue – which revealed just how little we actually understand about this long-term side effect.

Then it was off to Rotterdam and the annual meeting of the European Society of Surgical Oncology (ESSO). The session I was speaking in here was led by Prof Gerard van Oortmerssen, my colleague on the board of Sarcoma Patients Euronet. I looked at Patient Involvement in the context of an emerging partnership with professionals, taking the most strategic view I could think of. For me the conference highlights were hearing sarcoma surgeons describing and debating key issues which impact on them. They are very different from the oncology issues which tend to get a wider exposure. Although I must say that when Andrew Hayes (Royal Marsden) asked me to (effectively) summarise from a patient viewpoint an excellent debate he had with Marco Fiore (Milan), with no notice, I really had to think on my feet.

A week later and it was off to Madrid for SPAEN’s tenth anniversary. SPAEN hosted a dinner for the meeting of the EORTC Soft Tissue & Bone Sarcoma Group (STBSG) to thank them for the support members have given us over those ten years, for presentations and discussions at meetings, round table consensus consultations, and many one-to-one advice and information calls. We also had a board meeting and set out some of the challenges we have for the coming years.

The Dinner was held at the Madrid Casino, a beautifully decorative building. It featured the presentation of Lifetime Achievement Awards to four of our leading specialist doctors, Ian Judson (London), Peter Hohenberger (Mannheim/Heidelberg), Jean-Yves Blay (Lyon) and Paolo Casali (Milan). They have been unstinting with their support and advice during our ten years and this was a powerful way of saying thank you. They also embarrassed me with a similar award so I have included a picture of it.

Then came the NCRI Conference in Glasgow. The National Cancer Research Institute is the UK’s partnership of major cancer research funders and provides a forum for collaboration on strategies and developments which over nearly 20 years has proved very successful. An important element of its structures is the part played by patients and carers with ‘lived experience’ who come together in the NCRI Consumer Forum.

It is a conference dominated by science and advances in research, with crucial forays into advanced clinical issues where research and patients come together. The strong patient/carer presence is felt most as speakers address questions raised by their audience. Some of the toughest questions seem to come from patients and the challenges this can raise make this one of the most rigorous conferences there is. I had been asked to offer a patient view on developments in clinical trials and I faced the opposite of this situation with questions from two of the conferences earlier speakers with endless experience, Professor Mark Ratain (Chicago) and Professor Ian Tannock (Toronto) – very flattering.

The NCRI Consumer Forum held one of its three annual meetings at the conference and heard a exemplary joint presentation from Dr Helen Matthews (research biologist) and Max Williamson (a medical student) both of whom are cancer patients, about work they had done together. We also heard about plans to expand the role of the Consumer Forum from chair Emma Kinloch.

For the first time the Conference looked at a topical issue. Rather than a debate it was a discussion with presentations from four viewpoints to start it off. The topic was Assisted Dying and Cancer Care, chaired by Professor Sam Ahmedzai. I had the role of presenting a patient viewpoint, with the brief to be personal not detached or theoretical. It was an interesting challenge to take on and a privilege to be asked. The input from the audience was exceptional, with additional personal experiences from patients and doctors, a medical student explaining his reservations, and palliative care expertise from experienced nursing and medical professionals. This was a first for NCRI and indicates a way in which the conference might evolve valuable new approaches.

So, after seven weeks of seeming endless travelling and exploring the depths of airport terminals, conference centres and large hotels, how do I sum up what I experienced?

As a speaker I enjoyed the challenge of getting some very different messages across and I think my efforts were appreciated. As an attendee and delegate I learned a lot, especially about some of the advanced research now coming into clinical use – CAR-T cell being the obvious example. The evolution of clinical trials and adoption of RWE research is an issue which is becoming critical and needs greater attention. It was valuable to listen to other patients make presentations, and to hear presentations about patient issues, although I wish that presentations about patient involvement were given by patients, maybe together with a relevant professional, rather than by professionals alone. I was pleased with the advances being made in treating sarcoma, although this is slower than in most other cancers, something which may reflect the different underlying biology. And I was humbled to receive an award although I have to say it is nice to be ‘stroked’.

This was initially written to advise trainee oncologists on a training workshop.

Patient Consent Information

There is good guidance available on how to construct a Patient Consent Information leaflet. This includes templates you can follow.  Have a look at the following:

• http://www.hra-decisiontools.org.uk/consent/
• http://www.ctu.mrc.ac.uk/resources/patient_involvement/
• Downloading the template and guidance requires registration which is free.

This guidance from the UK has been developed through involvement of patients, ethical committee members and researchers.

Some advice about style (as opposed to content):

• Use simple language – guidance would be to aim for age 12 capability
• Use short sentences and short paragraphs
• Do not join different concepts – abolish “and” if you can
• Use short words – no more than three syllables in English, if you possibly can
• Avoid technical jargon – if you have to use them, acronyms MUST be spelled out
• Do not assume that the reader knows anything about research
• Do not make reference to other documents unless they are freely available

Within the structure and the constraints of content:

• Try and tell it a bit like a story – invite the patient to read along with you
• Start from something the patient understands
• Remember that all patients are different – you can repeat the story a different way
• Explain what the study is aiming to demonstrate and why
• Explain what will happen to them in the study – show empathy
• Answer the obvious “what if” questions in your text (eg. what if it doesn’t work?)

You take your pick on formatting advice, however:

• Use diagrams and tables to show issues clearly eg. schedule of hospital visits
• Use side-boxes to explain issues separately from the main flow of the story if necessary
• When formatting the sheet make it look inviting and easy to read
• Put a line space between paragraphs, don’t crowd text tight to the page edge

In the back of your mind:

Remember that the patient will only take one pathway through the study so complex issues like cross-over between arms in an RCT, or choice of successive therapies driven by response, need careful handling. A diagram can often help.

Ethics reviewers will want to see that you:

• Be clear about side effects – not just short term but any possible long term issues
• Be clear about reporting and managing side effects, including self-management

Dont rush:

• Give yourself time.  Draft, read and re-draft. Read it back 24 hours later
• Get others to read it, especially patients
• Have you been balanced in your explanation? Maintain equipoise
• It does not matter if key issues are repeated
• Remember that anything which appears to incentivise patients to enter the study will be unethical

Other issues:

• Does the study have a website? Give the URL
• Explain how to contact the research team – both email and telephone
• Explain how to act in an emergency, with at least two telephone numbers
• Have a card or sheet with contact details on it which patients can put on the kitchen noticeboard

Document management:

• Use document management to control versions until ethics approval is finalised
• Number the pages

 Passing ethical review:

Every ethical board has its own view of what makes a good patient consent information sheet. Almost everyone is agreed that page after page of legal statements should be at the back and that the first two or three pages is all that a patient will actually take in. Much of the rest will be read by family or friends. These first few pages are where the heart of the story must be told, this is where to place the diagrams they may need to refer to, this is where contact details should be (probably repeated right at the end). My personal view is that the first 2/3 pages should be like an executive summary, this is followed by the full story, then the statutory material. At the very end is a repeat of the contact details so that they can be easily separated from the main document as an aide memoire.

Roger Wilson                                                                                 

One of the challenges of patient advocacy is developing a balance between addressing immediate patient needs and creating a future which addresses the issues which patients see as important but which take time to change.

A good current example of the latter is the demand for earlier diagnosis. We have been voicing the need for twenty years to my knowledge and now it is government policy, cancer charities support sit, Public Health England has taken note, and the NHS is starting to consider how it can be done. It will take another five years before technologies, manpower and systems are fully in tune with the concept. One of the bigger changes involved is shifting the behaviour of some GPs.

When we discuss patient involvement we do not draw any distinctions between patient advocacy for the short term and the longer term.  The opportunities for involvement in research range from reviewing patient information for a simple research study to providing patient perspectives on multi-million pound strategic projects, with just about anything in between.

Lets be clear, the review of information about a ‘simple’ research study is important and valuable, just as informing those making multi-million pound decisions is valuable. Similarly the support for a patient having problems accessing a new treatment is valuable. These are all roles in the whole context of patient advocacy.

There is no scale of value in this but we do need to understand the differences and the implications that these differences bring with them. The main ones are the ability of the advocate, the training they have had and perhaps most importantly, their life experience prior to being involved in work as a patient. We do not assess these when we embark on involvement, and perhaps we should not do so as many people will grow into roles which are initially unfamiliar and their skills will rapidly develop given the chance to do so.

So I can hear you ask, why are you raising this issue?

There is one area where we are approaching a crunch. The dichotomy between patient advocacy viewpoints of short term issues of access to new treatments and the long term issues of the value of new treatments. We want a patient who believes there is value in a new treatment and whose doctor agrees, to have access to that treatment. At the same time we want to see the evidence of value in that treatment so that it can be appropriately used in the clinic in the future. Regulation is moving fast to accept data from short term Phase 2 trials with ‘surrogate’ endpoints, rather than favouring randomised Phase 3 trials (RCTs) offering statistical significance of effect based on an Overall Survival endpoint (OS). A short versus long term conflicting view.

Seeing new treatments come faster into clinical use meets the demand of most patient advocates. However most of them also fail to consider the cost in terms of long term understanding, the increase in risk which is implied, and the inability to control the cost of treatment through a meaningful understanding of value. Many advocates also welcome the reduction in the numbers of RCTs with placebo comparators; the placebo is generally disliked and there are questions about using data from such trials in the wider treatment context, something which information technology is increasingly enabling.

How do we move forward through this dichotomy? Quick and easy access versus long term validity and value.

The route being proposed by professional bodies, supported it must be said by many patient groups, is to develop means and methods to gather ‘real world evidence’. The idea is that a treatment can be given early access to clinical use. Data gathered from that use is analysed and used to review value, changing authorisations, pricing etc as seems fit. Many patients are stunned when told that does not already happen, so making it happen could be best described as ‘common sense’.

The means and methods do not currently exist. Let us see whether policy makers and regulators can make it happen. Maybe there will be subtle resistance from the pharmaceutical industry which currently gets it own way in such decision-making. I believe it is in patient interests to make it happen. 

That is a long-term advocacy project.