Tag Archives: research

Targeting and Trust: QoL in clinical research

Roger Wilson, a patient advocate and Honorary President of Sarcoma Patients Euronet

Roger Wilson, a patient advocate and Honorary President of Sarcoma Patients Euronet

I took a random selection of 20 abstracts from ASCO 2016. None of them mentioned that quality of life had been researched in the study but looking up the detail held in clinicaltrials.gov it turns out that 16 of them did have a quality of life component in them. Whether that will be reported when the study is published is a different question. Experience suggests that it will be mentioned, but that for the most part the detailed QoL data will go unreported.

These are the days of ‘big data’ in healthcare. Increasingly we are seeing databases linked, common standards being adopted to allow similar fields to be aggregated, and increasingly comparisons can be made between key outcomes. The International Cancer Benchmarking Partnership is providing fascinating comparisons on survival outcomes from several different administrations – and it is getting into the detail of differences in the ways that national data is gathered.

The first QoL in cancer study appears to have been in the 1970s. The first paper I could find which looked at developing a methodology dates from the 1980s. We now have a proliferation of methodologies dominated by the EuroQoL EQ-5D which gives the kind of generic background view needed for health technology agencies (HTA) to assess the value of the treatment. Other methodologies relate solely to the study to which they are being applied. Unfortunately for cancer patients, the EQ-5D is too crude report the kind of detail that cancer patients need to know to make informed choices about treatment. For that reason too it can only ever be part of the picture for HTA appraisals.

What do cancer patients need from quality of life information? The full picture of the impact of a proposed treatment in the context of the treatment pathway being followed. We want side effects information, how side effects are treated, and want to know how patients feel when taking the treatment in their own words, not those of some detached academic. We want to know about long-term side effects and what comes after if this treatment fails.

The pathway is the key issue in terms of quality of life – it is not a moment in time, it is life. However there are no data covering the succession of treatments, assessing the interactions that can arise as side effects aggregate, and the challenge of describing treatment and quality of life as end-of-life approaches is avoided.

I looked around to see whether anyone is aggregating quality of life data in a way which could provide this picture. No-one. Why not, after all there is at least 30 years’ worth of data around? The quick answer is the usual big data problem, different methodologies, data fields do not match, each study looks at the treatment being tested not at the patient. The pathway is ignored.

“No-one is aggregating quality of life data in a way which could provide this picture”

We are entering the world of targeted therapies. Targeting is a challenge for randomised studies: they can be unethical, either randomising patients when there is good evidence to indicate one arm is more effective than another, or using cross-overs, which invalidate the randomisation. Phase 2 studies usually do not include quality of life because there is no control group baseline with which to compare the treated patient. A strong response rate (60%+) is enough to ensure entry into clinical practice. One result is that patients are offered new treatments without being able to see a full picture of the step they are taking. Possibly just as important, health technology agencies are denied the whole picture of value which they need to make decisions.

Let us leave aside any questions about whether patients will accept such treatments – these issues disappear when survival itself is your primary challenge. Yet, as trials for targeted treatments reach statistical significance faster and with fewer patients than trials for traditional drugs, patients face increasing uncertainty about the impact of therapies they are taking. We need something to mitigate that uncertainty.

A first step would be aggregating existing QoL data to derive a picture of each cancer pathway, modified as clinical standards evolve. It would provide a baseline for comparing new treatments.

A second step would be using one tool/methodology for all QoL in cancer research. Agreeing that step when there are so many competing methodologies is likely to be difficult.

The third step would be requiring a relevant patient group to be the determinant of the measures to be adopted in each QoL study, small or large. Not easy to arrange but do-able.

A fourth step would be mandating full analysis and reporting of QoL data when it is undertaken in a clinical study. That should not be impossible.

If the cancer research community does not take on this challenge we could affect one of the binding factors of cancer care, trust between patient and doctor. Targeted therapy is an amazing development but we are journeying together into an unknown future built on that trust alone, something we haven’t done for more than thirty years.

We welcome contributions to this blog. If you have a topic you would like to write about, please send your post to Corinne Hall – chall@eso.net You can find our guidelines here – How to write a blog

 

 

It’s official: Top 10 research priorities revealed for brain & spinal cord tumours

stu farrimond portrait cropped

Guest blogger – Stuart Farrimond, editor of gurumagazine.org, blogs at realdoctorstu.com

What research should be funded and who should get the money? It’s a fifteen billion euro question – and the answer you get depends on who you ask.

When I practiced as a doctor I believed that medical research should always focus on extending life and finding new treatments. After all, saving lives was why I entered the profession. Emotional, psychological and lifestyle factors are of trifling significance by comparison… or so I thought.

Eight years ago my perspective underwent a seismic shift after I was diagnosed with a glioma – a malignant brain tumour. Only then did I start to realise that well-intentioned research efforts can often miss the point. Treating the tumour alone may extend life, but as a cancer patient I know that life is more than added years. All too often, researchers can set their priorities based on what they consider important, what tickles their fancy, or simply based on with what they have experience in.

Two years ago, Dr Robin Grant, Consultant Neurologist, at the Edinburgh Centre for Neuro-Oncology, set out to find a broader answer to the question of what brain and spinal tumour research should be prioritised.

He gathered key leaders in primary central nervous system tumours, each with a wide network of influence in their speciality, to establish a James Lind Alliance ‘Priority Setting Partnership’. Over the next eighteen months, a collaboration formed between representatives of all those affected by brain and spinal cord tumours: patients, carers, major brain and spinal cord tumour charities and multidisciplinary professional organisations.

The ‘Top 10’ list of UK clinical research uncertainties in brain and spinal cord tumours was developed by the partnership, drawing on the expertise and experiences of all those directly affected by the conditions. Last week, the list was officially launched at the British Neuro-Oncological Society annual meeting, with a call for the assembled researchers and clinicians, and crucially research funders, to use it to inform and guide their own actions.

Here it is:


 

Top 10 priority research questions in brain and spinal cord tumours

1. Do lifestyle factors (e.g. sleep, stress, diet) influence tumour growth in people with a brain or spinal cord tumour?
2. What is the effect on prognosis of interval scanning to detect tumour recurrence, compared with scanning on symptomatic recurrence, in people with a brain tumour?
3. Does earlier diagnosis improve outcomes, compared to standard diagnosis times, in people with a brain or spinal cord tumour?
4. In second recurrence glioblastoma, what is the effect of further treatment on survival and quality of life, compared with best supportive care?
5. Does earlier referral to specialist palliative care services at diagnosis improve quality of life and survival in people with a brain or spinal cord tumours?
6. Do molecular subtyping techniques improve treatment selection, prediction and prognostication in people with a brain or spinal cord tumour?
7. What are the long-term physical and cognitive effects of surgery and/or radiotherapy when treating people with a brain or spinal cord tumour?
8. What is the effect of interventions to help carers cope with changes that occur in people with a brain or spinal cord tumour, compared with standard care?
9. What is the effect of additional strategies for managing fatigue, compared with standard care, in people with a brain or spinal cord tumour?
10. What is the effect of extent of resection on survival in people with a suspected glioma of the brain or spinal cord?


 

The lengths that the James Lind Alliance Priority Setting Partnership process goes to in defining ‘Top 10’ lists is staggering. In March 2014, around 200 people (patients, carers and health professionals) submitted more than 600 research questions on the treatment and care of brain and spinal cord tumours they felt needed urgent answers. These were refined, formatted and consolidated, weeding out questions that previous research has already answered. The resulting 44 questions were then put to another sample of over 200 people to rank in order of priority.

Last November, 29 ‘stakeholders’ used these results to hone in on the ‘Top 10’.This is the point at which I became involved. As both doctor and patient, my priorities were conflicted: the “patient” in me wanted research that could help me deal with symptoms; my “doctor head” however told me that physicians desperately need better treatment data.

These tensions were borne out through the diverse mix of professional and lay representatives. The experienced James Lind Alliance facilitators have the diplomacy skills that could broker peace in any conflict situation and, after six hours of carefully organised voting, ranking and discussions, we finally selected our top 10. Looking back now, it is difficult to imagine a fairer, more representative way to set cancer research priorities.

Thanks to Dr Grant and other volunteers and workers involved in the process, these priorities can now help ensure that future research efforts will improve the lives of cancer patients. After all, improving lives is why we enter our profession.

 

We welcome contributions to this blog. If you have a topic you would like to write about, please send your post to Corinne Hall – chall@eso.net You can find our guidelines here – How to write a blog

War Against Cancer: the audited accounts

 


The truth in samll doses
Efforts to cure cancer are being hobbled by a culture that obliges researchers to think small and cautious while systematically overstating how much is being achieved.

Journalist and lymphoma survivor Clifton Leaf argues this case in his book The Truth in Small Doses: Why We’re Losing the War on Cancer and How to Win It.

His book is the culmination of almost 10 years of research, which generated a number of articles in Fortune, the New York Times and other publications along the way.

It is a call for a change in the cancer research culture, written by someone who knows what it is like to have their life hang in the balance, who believes in medical research, and who has devoted many years to trying to understand why progress is so slow and how we can do better.

In recognition of his achievement in opening up a lively and informed discussion within and beyond the cancer research community,  ESO awarded Leaf the first ever Best Cancer Reporter Lifetime Achievement Award, commending in particular his meticulous research and his ability to make sense of his material and tell the story in a way that is both compelling and constructive.

Resonance
The Truth in Small Doses is a joy to read, with a wealth of anecdotes that on their own justify the cover price. Like the one about the one-eyed surgeon, Denis Burkitt, who – in a goal-oriented collaboration with pathologists, virologists and an entomologist – solved the riddle of the aggressive tumours of the jaw that were killing so many children at his mission hospital in Kampala, with support from a £250 research grant, a 1953 Ford Jubilee station wagon, and a neighbouring hospital director who had a way with cars.

But Leaf also describes a world that cancer researchers are all too familiar with: endless applications for research grants; keen young scientists, full of ideas, obliged to focus on ‘safe’ well-explored topics, with enough a priori evidence to convince grant panels there is a good chance of a positive outcome.

Some points in the book are certainly open to challenge. When it comes to playing it safe, it could be argued that industry is more of a problem than academia. And while there are good reasons to argue, as Leaf does, for more research to be directed at tackling the disease at its earliest or precancerous stages, there are other innovative approaches with an equally strong scientific rationale that suffer the same neglect.

His core message, however, clearly resonates with a widespread sense of frustration within the cancer research community. Leaf speaks the truth, which explains why this book has been widely welcomed.

Going over the accounts
A financial journalist by background, Leaf makes good use of numbers to illustrate his points.

Numbers like these:

691 – the number of times “cancer breakthrough” was mentioned in the media between January 1990 and November 2003
71 – the number of new cancer drug approvals over the same period
45 – the number of approvals for new drugs (rather than new uses for existing drugs)
12 – the number of those new drugs that could show they actually helped keep people alive

Or these:

65,000 – the number of papers published by 2013 on p53
24,000 – the number of papers published by 2013 on c-Myc
$100,000 – estimated cost per study
0 – the number of cancer therapies based on these targets

Or on the process of applying for an R01 grant, the bedrock of medical research funding in the US:

260 – the number of pages in the Application Guide
23 – the number of steps in the application procedure
1 year – the average duration of an application process
1 in 10 – the chance of success

Or these, on the chances of becoming a principal investigator before your 36th birthday:

1 in 20 – the figure for 2013
1 in 4 – the same figure back in 1980

What the figures reveal, argues Leaf, is a culture centred on generating data that can be published rather than generating knowledge that could lead to a cure.

Everyone who wants to see faster progress in curing cancer, and young scientists who don’t want to waste their most creative years, have an interest in reading this book.

Clifton Leaf is deputy managing editor at Fortune. He will be formally presented with the Best Cancer Reporter Lifetime Achievement Award by Franco Cavalli, chair of ESO’s scientific committee, at the International Conference on Malignant Lymphoma in Lugano, June 2015.