Ask the right questions, get the right evidence

This is the second of my two thoughts about pressures being faced by patient advocacy.

There have been a number of recent articles in journals lamenting the failure of patient advocates to respect the principles of evidence-based medicine (EBM). It is a consistent low grumble from the science community, to which a small group are deeply wedded, while a majority probably have some sympathy with the point but also have some sympathy with the stance being taken by patient advocates.

There has been a change in the attitudes of regulators. Not that long ago they too were wedded to the evidence-base and they would maintain that this principle still underpins their decision-making. But in that decision-making, and therefore in the processes and procedures they employ, they are being more pragmatic. That has been partly driven by patient advocacy.

Some voices in the regulatory community are also identifying the issue which I believe needs to be addressed and which EBM protagonists seem to be studiously ignoring.  It is quite a big question.

Are we gathering the right evidence in clinical trials and in the way we measure and report real-world clinical care?

No-one in medical research seems to be addressing this effectively. A few are tinkering around the edge of the issue and for some, the idea that we are not gathering the right evidence, is like voicing heresy.

Cancer clinical trials are focussed on some measure of survival or tumour response to treatment. The so-called ‘gold standard’ measure of Overall Survival becomes difficult when a treatment is one of a succession of different therapies. A wide range of surrogate measures are used as a substitute. These are often dependent on some degree of investigator interpretation so are inherently unreliable, a factor which it is convenient to forget.  Side effects of treatment are an important issue and these are reported too, usually using an investigator applied judgement of severity against the CTCAE standards.

All this is a focus on objective measurement of the disease and the effect the treatment has on the disease. No-one is denying that this is important but where are the measures focussed on the patients themselves and the effect on them, their subjective reporting.

This is what patient advocates have been pursuing with their regulatory campaigns which the EBM stalwarts claim ignore the evidence-base. The advocates have an evidence-base in patient stories and anecdotes, but it is not one which they are in a position to measure, the professionals are not measuring it and have been ignoring it for more than twenty years.  So the EBM complainants, writing stridently about patient advocates not playing their game, would do well to look at themselves and their colleagues.

Are they asking all the right questions: are they gathering all the right evidence?

There is a side issue here about patient involvement. It is an issue which patient involvement cannot easily address and could be used as an excuse for inaction. Untrained involved patients do not necessarily see this ‘right evidence’ issue, they are often overwhelmed with understanding the planned outcomes and endpoints in a study. This assumes, of course, that they are consulted at a timepoint when they can actually input such ideas.

The second side issue is that we have much better ‘big data’ now than we have ever had. The ability to look at clinical practice across years, aggregating the experience of thousands of patients, means that retrospective analysis can provide valuable information and new insights. The question is, are we asking all the right questions in these analyses if the right questions were not asked when the data was being first gathered?

So the challenge for the data analysts is not to turn EBM into a self-justifying paralysis of ideas which ignores the patient?

Pressures are building on patient advocacy

Two pressures are building on patient advocacy. We do need to draw a line here between patient advocacyand patient involvement. The former are patients or professionals working towards a specific objective such as getting a new treatment approved, or raising awareness of an issue amongst politicians. That can be correctly called advocacy. Patient involvementis the drawing in of patients with ‘lived experience’ to a structure so that their experience based input, whether considered or ad hoc, can be taken into account alongside other views. There is of course no clear boundary line, partly because the same patients can be doing both. The two terms can be confused and issues which apply to one can also be inappropriately applied to the other.

What are these two pressures, and why are they unique to theadvocacyagenda?

The first is the influence of pharma companies, the funding they provide to patient charities and the influence that the funding opens up. There are regular, sometimes well informed, articles in both professional journals and the wider press raising concerns.

These concerns are real because recent history shows us what can happen. One example was a breast cancer charity that accepted funding for a policy post which actively promoted that pharma company’s drug to politicians and created patient activity supporting it. Quite often funding was sheltered through a local PR company.  Matters became more subtle in the mid 2000s and funding related to ‘projects’ rather than core activities. One not unusual ‘project’ was funding charity staff to attend an educational conference at a foreign and very pleasant venue, all costs covered. Regulations which required openness about funding followed and pharma companies now declare who and what they have funded in great detail. Charities have no such regulatory requirement from the Charity Commission although many do declare what they have received and for what purpose. Some healthcare charities will not accept industry funding at all and declare that policy openly. It is not tidy and while this lack of openness remains there will always be critics eager to point fingers at one or the other party.

Where this becomes an issue is with regulatory affairs. Patient groups and charities are often asked to provide an input to regulatory discussion, usually a paper, sometimes representation at meetings. Questions about financial influence are part of the preparation and a declaration of potential conflicting interests is requested. Some regulators are less searching than others.  Charities all have a different approach to completion of these requests and I do not believe that any regulator has a requirement that the CEO must sign the declaration.  Understandably charities which have little or no involvement with industry find these forms tiresome, not always understanding their purpose. The aim is not to eliminate input but to provide a perspective which reflects the real-life of working with and supporting patients. I have spoken with regulatory committee members who tell me they weigh up what is put forward by patient advocates at a meeting, taking into account the declared potential for conflicts of interest, but not discounting the input provided.

It is time matters were tidied up. The Charity Commission could regulate how charities declare commercial grants in their accounts and charities themselves could carry a declarations page on their website, as some already do. The regulators could work together to have a common declaration approach and individual advocates should make declarations (already required by some regulators) so that their personal situation is clear.

If there was this kind of clarity pharma company lawyers might be able to stop twitching so much and make the matter of financial support where it is proper, appropriate and open happen more easily. In addition researchers or journalists who get a ‘bee in their bonnet’ about inappropriate influences could be quietened, although I doubt they will ever be eliminated and, to be fair, the questions need to be asked.

The second advocacy influence is about understanding evidence-based medicine. It overlaps with the first issue above because some pharma companies could be accused of fostering a preparedness to ignore evidence. More about that in my next contribution to the debate.

 

 

Questions, questions … but can we get them answered?

Academic interest in patient involvement has been dominated recently by evaluation. We at last have a growing recognition that involvement is not an intervention, like sticking a needle in, but an influence over process which acts subtly and sometimes covertly to effect change over a period of time. There is rarely a single identifiable point of ‘impact’, the change may be subtle and only evident through reporting by those involved, researchers, managers, funders and patients themselves.

So what is the next challenge for our researchers? There certainly seems to be plenty of  content, the challenge is finding the questions to resolve.  Lets try a list of unanswered questions, not worded yet as proper research questions and to be fair, some might not make it that far:

  • How do we draw the lines between patient and public in involvement?
  • What is “lived experience” for the purpose of defining patient involvement?
  • How do we ensure we get the right people for the right role?
  • How do we report involvement as a key element of research?
  • If we sack an involved patient how do we report that?
  • What questions should we ask researchers to help find the value of involvement?
  • How should we ask researchers those questions?
  • How can we remunerate involved patients without creating conflicts of interest?
  • Are there ethical issues we should address to empower more effective involvement?
  • Is effective involvement pragmatic, or driven by philosophical and cultural change?

That’s ten to start with. I could go on.

One of the challenges is getting these questions, and others like them, aired. In this world of evidence based medicine research proposals are usually supported by a literature search from which the prospective funders can identify that the research question is a valid one. Thus research builds up in an organic manner, with a traceable provenance. In patient involvement there is little evidence, as yet, in the literature with the result that provenance is largely impossible to identify. One of the challenges for researchers who wish to raise questions like these, even as a commentary or discussion point for a journal, is that there is no evidence to point to that the question is important. The editor will not publish. It is a chicken and egg situation.

I am suggesting something which steps outside the usual ‘evidence based medicine’ criteria. As usual, remember that this is a patient making the suggestion, I have only one interest – getting questions answered so that patient involvement improves.

My appeal is that those journals which are happy to report or commentate on patient involvement, few but growing in number, encourage such new questions to be aired and debated relying only on the evidence that there is a question which informed people are discussing. The aim is that researcher groups will pick up on these ideas and have a reference base, however small, to work with when they seek funding for a full research project.

SOME THOUGHTS ABOUT THE NHS LONG TERM PLAN

I do not suppose that I am alone in finding that as far as cancer is concerned the NHS Long Term Plan, published on Monday, is admirable if somewhat underwhelming and, to be fair, cancer is only a small element in the whole. Its primary focus is on diagnosis.  There is no mention of the loss of valuable skills caused by Andrew Lansley as Secretary of State for Health in 2010-12, although work on Cancer Alliances to mend the damage proceeds.

The paragraphs on cancer in the Long Term Plan start with the following:

3.51. Cancer survival is the highest it’s ever been and thousands more people now survive cancer every year. For patients diagnosed in 2015, one year survival was 72% – over 11 percentage points higher than in 2000.

As a general point that should be borne in mind, even if NHS idiosyncrasy was not taken into consideration, evolution in clinical practice would account for much of that improvement. Indeed it can be argued that if progress on the 2007 Cancer Reform Strategy had not been politically diverted we would be showing even further improvement.  Things have obviously moved on and while not all of the 2007 ambitions were achieved the NAEDI National Awareness and Early Diagnosis Initiative, led by Cancer Research UK for the last 10 years, has been critically important. It identified many of the factors which result from the behaviour of patients, GPs or the wider NHS, in the diagnostic process and it underpins what is now planned.

The NHS Long Term Plan has these promises.

Assuming that full funding for these developments is forthcoming in practice and that staffing issues for radiographers, radiologists, pathologists, laboratory staff, nurses and oncologists of all kinds are addressed (given the effects of the B word) this will be a very welcome development and will go a long way towards meeting the cancer survival ambitions.

There is however a shadow, identified in the Health Foundation report Unfinished Businesspublished shortly before Christmas. This is the role of GPs as ‘gatekeepers’. Those with undiagnosed cancer rely on a GP having suspicion and initiating tests (the right tests) or making a referral. That will not alter although the frustrated will be able to self-refer to a Rapid Diagnostic Centre. These will certainly pick up some of the otherwise undiagnosed but not all. Indeed there will be some who attend a Rapid Diagnostic Centre who may not be diagnosed early – a small percentage of false negatives come from almost any test, there are always interpretation issues and some rare cancers have barely discernible characteristics at their early stage.  So from a patient viewpoint this is a welcome step forward but quantifying its potential is massively uncertain and success will rely on the skills levels available in the Diagnostic Centres, especially those located at a distance from a major cancer centre.

3.52. This Long Term Plan sets a new ambition that, by 2028, the proportion of cancers diagnosed at stages 1 and 2 will rise from around half now to three-quarters of cancer patients.

In 2007 we could not have stated an ambition in those terms. This target comes from the work that has been done on data, initiated in 2007. The National Cancer Registration & Analysis Services is a world leader in cancer data. In each tumour type the push to record staging data at diagnosis in the initial cancer registration is resulting in a much more accurate picture of prognosis at diagnosis. This can be compared with the eventual treatment outcome and also provides for targets such as this one.

The NHS remains excellent at creating ambitions while overlooking some of the issues. There are two things evident in the NHS Long Term Plan. First, it is not a plain English document.  Second it did not involve independently minded patients in its development but we have now come to expect that. Patient involvement has been reduced to tokenism in NHS cancer service provision. It cannot be described as patient-centred any more and a key weakness of the whole structure is that the voice of end-users is missing. The charities, good as many of them are, are not a substitute.

On the matter of creating ambitions while overlooking some of the issues I find it hard to believe that a faster diagnosis standard for sarcoma will emerge without resourcing specialist sarcoma units to handle it. Pathology skills, one example, are already at a premium. Over 50 primary diagnoses, with many variants by location, histology and surgical feasibility, suggest that words like “all” and “full”, which appear throughout the new plan, could be unrealistic. The case for genetic profiling to take over the challenge has no evidence base and apart from profiling the whole population I cannot see it working for sarcoma. I should like to be proved wrong.