Category: Clinical trials

How did we get into this mess?

Earlier in the year I commented on the achievement of an important academic clinical trial, STAMPEDE, which showed that docetaxel given as soon as a prostate cancer patient relapses can give up to 22 months extra life (even more for some patients). NICE says that the drug should only be given after hormone therapy has stopped working. It will take NICE a year or more to re-visit its guidance but NHS England can make a decision to issue guidance which changes practice immediately.

It is three months since the study was presented, although the inevitable delay until it is published means that the scientific paper is not yet available. However that “immediate” decision is not forthcoming.

The delay in getting docetaxel into earlier use in relapsed prostate cancer is unbelievable bureaucracy. The data are not in doubt. The study was funded by Cancer Research UK and the Medical Research Council – blue-chip funders. The investigators were our top research clinicians in prostate cancer, led by Professor Nick James from Birmingham. What is more, it is likely that the relatively small costs of the change will be at least balanced by savings in care costs.

This is a gross betrayal of the goodwill of patients who enter clinical studies.  

For those of us who enter studies the altruistic component in our decision-making is significant. We want our contribution to be better treatment for later patients, assuming that better treatment is proven, and we are happy to take that risk. This study is a superb tribute to the patients who entered STAMPEDE. The NHS England delay is an appalling abuse of power.

For a bureaucrat, whatever pompous title he may carry, even if it is Secretary of State, to delay a change in treatment practice betrays all patients entering clinical studies.

Let no-one in Government be in any doubt that this delay also damages cancer research, contradicts everything it says about having targets for cancer survival, and shows that what it says about increasing efficiency is boloney when it comes to actual treatment.

Patient Involvement in Cancer Research – a cause for concern

We are seeing a real shift in patient involvement in healthcare research. It is very encouraging to those of us that have been involved for a decade or more to see how the word is spreading. This is despite the relative disinterest in it shown by the current UK government. Its predecessor was an encourager and ensured that small pots of cash and other resources were made available at crucial moments. The disinterest is perhaps most noticeable in cancer research, for long a leader in the field of patient involvement – not the only leader it must be said but probably the most prominent.

The main organisation in clinical cancer research and the management of late stage trials was the National Cancer Research Network (NCRN). It is the organisation that raised patient accrual into cancer studies from 3.5% of incidence to well over 20% of incidence, a world leader. It is now no more – subsumed into the National Institute for Health Research Clinical Research Network structure.

(For acronym watchers this abbreviates to NIHR CRN. It has a Co-ordinating Centre for which you add CC. I believe it is the current leader in the NHS’s secret competition to adopt the longest acronym.)

There are now 30 speciality areas in healthcare research under the wing of the NIHR CRN. Looking at the list of specialities it is impossible to find one where advances in care informed by high quality research is not desirable. Most have a disease focus, a few such as Critical Care and Public Health have a broad remit across a wide range of diseases. None is as large as cancer in terms of the number of studies underway, or the amount of cash invested, or the range of research funders, or the number of industry funded studies which are accredited for NHS support. However all are shoe-horned into the one over-riding structure.

There are now 15 geographical networks. Cancer research used to have 30 local networks each with a patient ‘partnership’ group. Other diseases had differing numbers of networks, with lots of overlaps and some of them did not have national coverage. This government’s approach to simplifying things has forced everything into one structure, ditching lots of expertise and muddling priorities along the way. Each of these plump ‘no longer local’ networks has a patient involvement strand but because of costs the recruiting tends to be around the geographical centre where the network has its headquarters. There is, of course, no guarantee of any involved patient having the specific disease experience that a researcher might like to call upon.

At a national level patient involvement in cancer research has shifted from NCRN to NCRI. The ‘consumer’ group was always called an NCRI group, even though it was run by NCRN. It has also changed its name to the NCRI Consumer Forum. Membership is largely the same but retirements and the need for continuing recruitment to CSGs means that a high proportion of members have been recruited in the last year. The big problem is that funding from the government has been lost. All credit to NCRI members who have agreed a budget and to NIHR CRN CC, which has contributed. The NCRI has also become incorporated as a charitable organisation, with a board of Trustees which includes a patient and is chaired by the CEO of a patient charity. Its members are its funders, not directly represented by the Trustees.

This is a story of the steady wearing down of patient involvement resources hidden through structural changes and shifting budgets. Getting clinical research into one amorphous structure to the disbenefit of cancer research may appeal to NHS control freaks and the envious. Cancer research is disliked by many in other research areas because it is so large and consumes such large budgets. I have heard the argument that it has been a favoured child for too long. Creating a bland giant in which it has to fight for every bit of territory appeals to some. Allowing nationally funded patient involvement in cancer research to wither away probably pleases those people.

The importance of patient involvement in the development of new studies is now undeniable. Researchers are required by many funders to demonstrate how the user community has influenced their study and patients sit on the award panels of all kinds of research funders. In cancer the peer review process through the NCRI Clinical Studies Groups includes patients and carers, a ready resource immediately available to researchers following that route. However there is no certainty that funding for that immensely important resource will continue.

Independent Cancer Patient Voice (ICPV), a small charity supporting patient involvement in research, responds to a steady stream of researchers wanting different kinds of involvement in research, from looking at initial ideas, reviewing patient information leaflets and providing membership of trial steering groups. Presumably these researchers can no longer find that expertise in the patient groups in their big bland otherwise distracted local research networks – surprise surprise!

The growth in pharmaceutical company interest in having the views of patients is also noticeable. Novartis has undertaken a pan-European project EPALCO to make the company more patient-focussed, although because many of its studies are designed in the USA where patient involvement is almost non-existent, there are still some barriers to overcome. Astra Zeneca and Amgen are two other European pharmaceutical giants with relatively advanced ideas being actively explored. The lesson here is that the pharma companies usually fund this work.

So patient involvement in cancer research is increasing but the resources available are disappearing. ICPV bears a growing burden, at no cost to the research community and its members give their time free of charge. There is a strong core NCRI group which government has stopped funding after twelve years and seems ready to allow to wither away.

This must be a concern for the NCRI Trustees. What a depressing contrast with all the high sounding words from ministers about healthcare being centred on the patient, about sensitivity to patient needs and the importance of research delivering what is of value clinically.

Richmond Pharmacology and the HRA – what was it about ?

Something quite extraordinary has happened in the last couple of weeks which has barely attracted any attention in the media.

I am sure that many of you, like me, were very confused by the High Court action taken by Richmond Pharmacology Ltd against the Health Research Authority (HRA).

It seemed to go on for months (it did), the issues in contention were not clear (they kept changing), and the outcome appeared to be that Richmond won, although the Judge has yet to decide on what actions to recommend.

What was at stake was the transparency of clinical trials. The openness of everything from registration to results. Richmond appeared to have set itself up as a voice for the pharmaceutical industry. However the industry effectively disowned it and made it quite clear that Richmond was on its own.

The Judge made a declaration that the HRA has acted unlawfully because material on its website is “ambiguous and potentially misleading.”

The Judge was heavily critical of Richmond Pharmacology for not being clear about what they were arguing for until their very final submission to Court. He criticized them for introducing new arguments at a very late stage.  There were many broad points that were dismissed in 5 months of intense legal argument, in a process that cost hundreds of thousands of pounds. There were continual challenges to the standards which have been developed to create clinical trial transparency.

The main argument Richmond (at the last minute) had asked the Court to rule on was that the HRA is acting unlawfully by asserting that there is an overarching legal requirement for everyone running every clinical trial to register it. The Judge is clear that the HRA never claimed there was such an overarching legal requirement. Phase 1 trials, which is the area where Richmond Pharmacology works, are exempted at present, although EU law may change.

Richmond has ended up with an order which says that the HRA’s website had some ambiguous wording.

Richmond had claimed during the five months of argument that high regulatory standards on trials are making the UK a less competitive place to do research. There are growing concerns about unreliable data from clinical trials, especially when trials are run at low cost in countries with weaker standards. The one thing the UK can compete on is quality and integrity. The Judge’s decision supports that position. We are not in a race to see how far we can compromise standards.

The HRA’s position has been made stronger by the judgement. The Judge says it has a clear legal right to check researchers’ compliance with ethical and legal requirements to register and publish clinical trials. It has a mandate to continue its work raising awareness of researcher’s requirements to register trials and to check researchers’ compliance with those requirements.

Similarly the judge made it clear that people conducting trials have ethical obligations, as well as legal ones. He said the HRA is entitled to apply sanctions where ethical requirements have been breached, as long as it is clear about what those requirements are and what the sanction would be.

Richmond Pharmacology has said little about this case themselves, although their lawyers have inevitably crowed over winning the case on their website. So where were they coming from ? Who are they ?

Richmond Pharmacology Ltd is one of the largest clinical research organizations (CRO) in the UK. They are a commercial provider of the facilities and expertise for Phase 1 clinical trials. They have no investigator led research, their clients are largely pharmaceutical companies. Their facilities are in south London at St George’s University Hospital (Tooting) and Croydon University Hospital. They are therefore a tenant of the NHS and pay substantial fees for the facilities they use.

The Directors of the company own the company and are the doctors who lead the clinical teams, so it is a hands on operation. They turnover about £10m a year and like any small privately owned company have been through ups and downs and have learned how to survive. So what brought about this extraordinary legal case ?

I have never before seen a small company set itself up as the champion for a multi-billion dollar industry, only to find itself dis-owned by that industry. Richmond Pharmacology had nothing to gain from winning any part of the case at all. Misguided altruism? Surely not. What they have won is so easily sorted that it could be called trivial.

Until they actually say something it will remain a mystery. No openness at all, perhaps that’s no surprise. What is no mystery though is that the HRA has massively drawn on public funds to defend itself. An explanation for why that was necessary is the least the public deserves.

Can we, the public, exert any pressure to ensure that happens? Perhaps we should discourage people thinking of joining a Richmond clinical trial.