Publication of all results from clinical trials

Publish all Clinical Trial Results

Hazel Thornton drew our attention to the correction to the NEWS item published in the issue of the BMJ: Patients are urged to boycott trials that do not guarantee publication.

 

The correction reads:

"This News story states that the Cochrane Collaboration backs the alltrials.net initiative, but the organisation has yet to officially sponsor the campaign (BMJ2013;346:f106, doi:10.1136/bmj.f106). It also says that the Centre for Evidence-Based Medicine is at Bond University, when it is in fact at the University of Oxford."

BMJ Editor's Choice

Timely publication of all trial results may mean less overtreatment

Fiona Godlee, editor, BMJ

fgodlee@bmj.com

Two BMJ campaigns coincide this week: for publication of all results from clinical trials, and against overdiagnosis and overtreatment.

Sentinel node biopsy (removal of the sentinel lymph node) is widely used to stage disease in patients with breast cancer and malignant melanoma. It carries a risk of lymphoedema and other complications, which increases if patients with positive sentinel nodes go on to have further lymph nodes removed in an effort to improve their survival. Evidence from several large trials has saved women with breast cancer from having axillary lymph node dissection if they have no clinical signs of axillary involvement: the trials found no significant difference in overall or disease free survival when axillary dissection was added to sentinel node biopsy.

But as Ingrid Torjesen reports, patients in the United Kingdom, the United States, and elsewhere who have malignant melanoma are routinely undergoing sentinel node biopsy, followed by regional lymphadenectomy if the biopsy is positive (doi:10.1136/bmj.e8645). This is despite guidance from the UK’s National Institute for Health and Clinical Excellence that there is, as yet, no published evidence from randomised controlled trials that sentinel node biopsy improves survival.

What trial evidence there is comes from the Multicenter Selective Lymphadenectomy trial (MSLT-1). Five year follow-up data published in the New England Journal of Medicine in 2006 found no overall survival advantage in patients who had sentinel node biopsy compared with those who didn’t. But controversy has arisen over the authors’ claims of improved disease free survival. These claims are based on a lower rate of nodal recurrence in the biopsy group, but critics say this finding is unsurprising, since the patients in the intervention group who are most at risk—those with a positive sentinel node—have had their regional nodes removed.

The researchers promised further analyses after 10 years of follow-up and at an interim point, and had these been published as expected in 2008 and 2011, the controversy might have been resolved by now. But these data have not yet been published. The authors say they are working on their analysis. Meanwhile, sentinel node biopsy has become the standard of care in many countries. NICE says the procedure is justified only in the context of clinical trials, but Torjesen has learnt that it is carried out in at least 19 trusts in England, only two of which are involved in ongoing trials. Is this another example of harmful overtreatment? Only the trial data will tell.

This is not the only case in which clinical trial data have been published late or not at all. In addition to the well documented suppression of data by drug companies, there are clear examples of delayed or non-publication in non-industry sponsored trials. Last week we reported on the long delay in publication of a trial of deworming and vitamin A that was completed in 2005 (BMJ 2013;346:e8558). This week in an editorial we reference a large trial of adenoidectomy that has only just reported after nearly a decade (doi:10.1136/bmj.f105). The editorial calls for ethics committees, funders, and institutions to take responsibility for ensuring that the trials they approve, support, and host are published in full and in good time. Working with others, we are taking the campaign to patients and the public. If you agree that all clinical trials should be published, sign the petition at alltrials.net.

Cite this as: BMJ 2013;346:f159

Call for release of all drug trial results

The Times – 10.01.2013

The failure of academics and pharmaceutical companies to release the full results of clinical trials is stifling medical discovery and putting lives at risk, doctors say. The British Medical Journal is calling on the public to sign a petition at alltrials.net demanding the results of all trials be published.

Dr Ben Goldacre said that the petition was a response to “years of foot dragging” around what he described as the “biggest systemic flaw in evidence-based medicine”.

“For 20 years now, people have claimed this is being fixed,” he said. “People have acted as if this is an embarrassing secret, that should only be discussed behind closed doors. But that approach has demonstrably failed, so now we are making it public.”

At present, doctors and researchers do not have access to the full results of clinical studies. With approximately half of all trials conducted on patients never published, this means that doctors prescribe drugs without the full available evidence, or worse, with misleading evidence.

“The best available evidence shows that studies with positive results are twice as likely to get published,” said Dr Goldacre. “Those with negative results are more likely to go missing in action, so doctors see biased evidence. When we are misled about effects of treatments, we cannot make the best decisions for patients.”

Supporters of the petition argue that this means information about the efficacy of drugs — and the relative importance of side effects — is lost, but also that trials are needlessly repeated, by researchers who are unaware they are replicating prior work. They are also asking for the release of all the relevant previous results on all drugs still currently being prescribed.

“Most of all, the current situation is a betrayal of the trust that patients, and trial participants, place in us,” said Dr Goldacre. “Patients participate in trials, sometimes enduring extra discomfort or inconvenience, because they believe the results will inform practice and help others in the future. When the results are buried, those patients have been misled. We need people to participate in trials, but we can’t ethically pretend that this problem doesn’t exist. We should either make sure all the results are published or be honest and say, ‘If the researcher or sponsor company doesn’t like the results we won’t publish’.”

One of the most-cited cases of results being withheld is with Tamiflu, an antiviral drug produced by Roche. Dr Carl Heneghan, Director of the University of Oxford’s Centre of Evidence-Based Medicine, works on the drug, on which the UK government has spent half a billion pounds. He believes that because of a failure by Roche to release full clinical trial reports, despite promising to do so, we still don’t know if that was money well spent.

“We’re still awaiting data from Roche which they have refused to give us for years,” he told The Times. “Eight of the initial ten studies into the drug were never published. When we asked Roche for them they refused to make the full study results available. We’ve spent £500m on Tamiflu and we still don’t know if works.”

“When data is withheld it can look initially that a drug is promising. However when full data is available, we might realise that there are more harms than benefits. Any treatment we use is about the relationship between how much it benefits a patient and how much it harms them. That ratio is incredibly important. The withholding of data skews this. We will look back in 20 or 30 years and think what we do now is ridiculous.”

· Sense About Science’s petition can be signed at alltrials.net

Belfast

Travelling to Belfast for the official opening of the Northern Ireland Molecular Pathology Laboratory and the Northern Ireland Biobank.

Remarkable initiative by Jackie James and Manuel Salto-Tellez that brings together the hospital diagnosis with research and the university.

Excellent work in engaging and working with the Hospital Trust to see research as part of the patient pathway - a standard part of the journey.

As patients this is a major step forward as it places research in the realm of quality standards and patient experience. A right of passage rather than an optional extra.

But it also means that, as patients, we should be asking about research - what studies can I take part in?

And if there isn't research into my illness, condition or disease - why not?

Plus, is full use being made of the biomedical samples that I have given? Are they being used for research and what good is being extracted to help future patients?

WATCH HERE: http://www.u.tv/News/Queens-cancer-lab-could-save-lives/d7090e4d-e744-4df1-826e-5a5a72edb614

http://goo.gl/IyaEt

I gave a talk and facilitated a workshop for researchers and others about effectively involving the public in the work - the advantages and challenges.

The Centre has worked closely with patients and patient groups to help them shape the service and make it a central part of the local NHS. They have given tours, helped raise considerable funds for the IT digital imaging. They see research, the University, the Trust and their patients as an essential and working partnership. Research is core to patient care.

Clinical Trials Data - Commons Select Committee Consultation

Happy new year to everyone. I am pleased to say that I am finally getting over the flu which meant that most of the holiday was obliterated.

I received the following from Sarah Qureshi today. Please respond.

Science and Technical Committee (Commons)

Transparency and disclosure of clinical trial data have been topical recently, in part due to the recently published book 'Bad Pharma', by Dr Ben Goldacre. It highlighted that pharmaceutical companies are entitled to conduct numerous clinical trials on a new drug but publish selectively, thus skewing the evidence base available for doctors and patients seeking to make informed decisions.

The Committee is seeking written submissions on the following:

1. Do the European Commission's proposed revisions to the Clinical Trials Directive address the main barriers to conducting clinical trials in the UK and EU?

2. What is the role of the Health Research Authority (HRA) in relation to clinical trials and how effective has it been to date?

3. What evidence is there that pharmaceutical companies withhold clinical data and what impact does this have on public health?

4. How could the occurrence and results of clinical trials be made more open to scrutiny? Who should be responsible?

5. Can lessons about transparency and disclosure of clinical data be learned from other countries?

Deadline is noon Friday 22 February 2013. Please see link below for further details and how to submit written evidence:

http://www.parliament.uk/business/committees/committees-a-z/commons-select/science-and-technology-committee/inquiries/parliament-2010/clinical-trials/

Kind Regards,

Sarah

Sarah Qureshi
Partnership Manager

Please note: New address and phone number

UK Clinical Research Collaboration
C/O Medical Research Council
One Kemble Street
London
WC2B 4TS
T: +44(0)20 7395 2271
E: Sarah.Qureshi@ukcrc.org

Visit our website at: www.ukcrc.org

Research and Commissioning

Please note that I will be adding further questions to ask - if tweeting include #involve2012. Commissioning is fundamentally about spending money so I thought I would throw in a few coins especially after Sir Iain Chalmers' blistering attack on waste in research at #involve2012. So, I have added some questions to ask...

The new Mandate to the NHS Commissioning Board was published earlier this week whilst we were all at INVOLVE

The Mandate sets out the objectives for the NHS and highlights the areas of health and care where the Government expects to see improvement. It focuses on the areas that matter most to people:

- helping people live longer

- managing ongoing physical and mental health conditions

- helping people recover from episodes of ill health or following injury

- making sure people experience better care

- providing safe care

RESEARCH is mentioned as follows...

6.2 The objectives in this mandate can only be realised through local empowerment. The Board’s role in the new system will require it to consider how best to balance different ways of enabling local and national delivery. These may include:

·       its duties to promote research and innovation – the invention, diffusion and adoption of good practice;

7.2 The NHS Commissioning Board’s objective is to ensure that the new commissioning system promotes and supports participation by NHS organisations and NHS patients in research funded by both commercial and non-commercial organisations, most importantly to improve patient outcomes, but also to contribute to economic growth. This includes ensuring payment of treatment costs for NHS patients taking part in research funded by Government and Research Charity partner organisations. 

We need to push the NHS to make sure that research opportunities are explained to patients.

Please check with your local Trust and new Clinical Commissioning Groups to make sure that they are complying with their duties and whether they are reporting activity.

All NHS Trusts have a duty, through the NHS Constitution, to promote opportunities for patients to take part in clinical research studies. 

The National Institute for Health Research provides support for the delivery clinical research trials in the NHS in England, and there are now new measures of how individual Trusts are delivering on that duty across the different therapy areas.

THE KEY REPORTING AREAS are

1. How many clinical research studies the Trust took part in last year 2011/12? And currently?

                                                                                                                                                    

2. How many patients it recruited as a Trust?

3. How much research is being done across a range of medical conditions?

Clinical Commissioning Groups (CCG) are committed to promoting patient recruitment to and participation in research according to section 4.2.2 of the authorisation process.

A statement we might expect to see from CCGs 

“We declare that our CCG understands and will comply with our statutory responsibilities regarding promoting research; and that we are committed to following the policy of ensuring that the NHS needs the treatment costs for patients who are taking part in research funded by Government and research charity partner organisations”

Some Useful Sources of Information

A Clinical Commissioners Guide to the Voluntary Sector

http://www.nhsalliance.org/documents/view-latest/

Resources for Health and Wellbeing Boards http://goo.gl/aCz41

Healthwatch England http://healthwatch.co.uk

NHS National Commissioning Board  http://www.commissioningboard.nhs.uk

Patient & Public Involvement - A Waste of Time?

Patient and public involvement - a waste of time? Have we squandered opportunities? Have we drained hope from many of those who became involved?

Well, to be quite honest, I still attend too many meetings, review too many research proposals, see and hear examples of tokenism, inappropriate behaviours and quite frankly dreadful involvement. Pleasingly, there are more and more examples of good practice but they are far from universal.

I have been involved for over ten years and I believe that many things have got better. The culture is much improved, the climate is more friendly and we are increasingly gathering evidence of impact, BUT, we have to find a way of...

Improving Research - Together

If we are going to transform research we need to work together. We should start this dialogue by turning the page from the separate worlds of the patients/carers/public on one side and those people employed in research on the other. We need to avoid labelling ourselves with our illnesses and work together for all those who currently need care and treatment.

Quite simply, we should all want to make a difference, whether by working in research, raising funds through various activities, being actively involved in shaping studies or taking part as a participant in relevant clinical trial. We ought to hope that our actions lead to the developments in research and do not want to be part of any tick box, duplication or unnecessary activity.

The world of research is far from perfect.

Ben Goldacre's excellent book Bad Pharma catalogues major issues around missing data, bias in publication and lack of openness that are an indictment of outrageous and unacceptable behaviour akin to many other recent public scandals. These must be taken up, challenged and addressed. 

There are, even now, a few people who seem uninterested in dealing with these problems, some are more interested in working on their own, gaining kudos from published papers, acquiring funding for their institutions or organisations rather than seeing the greater good and potential of collaboration. 

Similarly, I feel that charities that do not fully involve people in helping to identify the priorities for research are morally wrong. The charity rules of 'public good' should not be interpreted as just doing things for or to people but 'with' the public. 

These instances, however, should not stop us from working together especially with those who want to see improvements. In fact they should actually force us to work more closely to tackle these issues, correct the wrongs and move forward. This does not mean that we have to necessarily agree all the time yet we can learn from each other.

The direction for this transformational approach ought to be a statement of on the overall importance of honesty and transparency in research, about the need for high quality studies and the value of systematic reviews.

It is then crucial to identify those challenges that we have in common and work in partnership to create, a movement for change leading to improvement in the experiences of treatment and care for future patients, their carers and families.

Without a clear purpose to working together we are likely to waste the chance to make a difference.

The focus needs to be a dialogue where we can all be informed by the insights and knowledge that we each bring from our differing perspectives. This can no longer be a one-way process where patients, carers and members of the public are invited in to help inform research. We have squandered opportunities to change things whilst promoting public presence on committees.

Too often we have brought patients, carers and the public into the discussion after the event – to learn in hindsight. There is value in this and lessons to be learnt. Sometimes we involve the people to gain insight – e.g from patient experience. But wouldn’t it be better if by working together we could consider foresight – e.g. “Let’s ask patients what research they want, whether this trial is practical, etc.”

If we want to get to foresight then we must become more specific about...

What it is we want to improve?

·      Is it policy and direction, the organisational structures and/or aspects of the research process and individual projects?

(These require different approaches and we have to be clearer about each context, and purpose, impact and benefit we seek to achieve)

How the public voice can be heard?

·      How should to inform, form and influence research and where should it be listened to for best effect?

(These approaches need separate planning and we need to be clearer about our role and responsibilities)

What is required to enable those voices?

·      What learning and development opportunities are needed/wanted?

(These must state a common understanding of learning and move away from training people to be ‘like researchers’)

In each and all of these we must ask how we implement equality legislation and address health inequalities.

Of course, I want to shout the phrase 'no decision about me without me' and yet I also want resources spent on treatments and not on unnecessary consultation or inappropriate involvement.

Although I support the demographic entitlement of involvement we have to spend money and time more wisely. It has to be about what can be gained and achieved by involving different individuals, groups and communities in developing healthcare research to improve service delivery. This should make us question paying people to attend meetings unless there are clear outcomes.

Most people want to know that their voice is heard; that their experiences are used to effect change; that feedback is provided about what happened as a result. The degree of their involvement may be quite small and make a huge difference whereas other may want to play a larger part and change things slowly over time.

I do not get the sense that mass numbers of the public want to be actively 'involved' by sitting on committees. I would go further and say that committee representation attracts too many people like me who like to understand organisational structures and processes, are able to express their views with some clarity yet are mainly white, middle class and retired from a professional background.

There is nothing fundamentally wrong with these characteristics. Well, I would say that wouldn't I? We do have a part to play but a richer, more culturally diverse, robust dialogue is required about the value, aim and practicality.

Social media offers as much potential as real active local community action. It is not a question of either / or but with new regional structures there are opportunities to do both in a coherent and joined up manner.

We, who are involved, must be advocates for the many different effective forms of involvement and engagement. We need to invite those we interact with to get inside local communities, to use a variety of methods for involving people and to make better use of social media.  We have spent time learning about research and now it is time we helped the researchers learn about people. We should help ensure that the involvement is appropriate and proportionate.

Public lay members of research meetings must shift away from 'being the lay representative' to being an advocate for involving people in the whole process, advising on different types of engaging and involving as well as helping groups to make those connections.

We who are involved have to ask better questions of ourselves, our involvement, the groups on which we sit and the attitude, behaviour and actions of the NHS. It needs to become about leadership rather than representatives. It is a shift towards advocating for the patient voice and becoming activists for change.

This means we need to give greater consideration as to how we help others to use their voices, develop their skills and build their confidence rather than necessarily being the voice. In this way we might make the very best use of our time and efforts.

I shall stop here as I think the next part of this blog mini-series will be about learning and development. Thank you for all the very positive emails about the Obituary for PPI.

I'm_patient

The INVOLVE Conference in Nottingham next week offers an opportunity to take the practice of working together to improve research through transformational change. 

I am supporting a poster about Building Research Partnerships, the work being led jointly by the National Institute for Health Research - Clinical Research Network and Macmillan Cancer Support. Great leadership from Karen Inns and Jack Nunn from the respective organisations.

I am also supporting, at a distance,  Lessons for the Future - Roger Steel and Zena Jones - Session 6.1 - in looking at the risks and benefits of a more business like approach to organising our work.

But I am also hosting a discussion session 6.7  From Acronyms to Actions. My recent Blog - An Obituary for PPI has prompted this discussion so I thought I ought to say again in a poem....



Involve to Influence

I was a patient
Cancer, throat, long time ago
Speaking roughly
What would I know?

I'm a patient
Threatening, conditions, life
Important values
That's what I know!

I'm Patient
Involved, engaged, advocating
Listening closely
To know what I know.

Impatient
Action, improvement, change
Transformation time
Speak what 'you' know

An Obituary for PPI - A Challenge for Change

"Who killed PPI?" I ask.

"Was it I?" enquired the tetchy tweeter @ppisqueek.

"Is it time to say farewell to PPI? Has it had its day? Deceased, gone before? Have we come to Polly Parrot Internment or is it Pointless Pigeon Inhumation?

"A kindness", some say. 

"How dare you!" say others.

Well, that may just have got your attention and hopefully encourage you to read, consider and comment on the current state of affairs described in this article.

When I say PPI, I actually mean the sole use of those three damned letters. 

It is an acronym that prevents progress. The ever present and indiscriminate use of this shorthand means that we lose sight of the real purpose of being a movement for change and making actual differences to NHS research, treatment and care. 

"Oh, we are doing PPI, we have a PPI strategy, we have PPI representatives on our committees, we have a PPI reference group and PPI is on every meeting agenda." I am sure that you can add some more! In fact, please let me know more examples of this dreadful misuse of our time, maceration of purpose and maligning of effort.

The statements suggest that 'doing PPI' is sufficient. This allows a number of people to believe that the involvement of the public, carers and patients is somehow different and separate from improving healthcare. It creates a PPI machine producing more of the same PPI. A factory of futility.

The interpretation of 'doing PPI' is as frustrating to many health professionals as it is to members of the public (choose your own subset of service user, patient, etc, etc.) who want to Make a Difference.

I had cancer 17 years ago. It seriously affected my health, my work and my family. I wanted to help in any way to improve cancer services and began some 13 years ago by being a member of a local health forum.  I wanted to see improvements made in health treatment and care. I had no desire to 'do PPI'! 

I want improvement.

I have come to understand that high quality research has the greatest potential to result in people receiving the best care. It means that the care, advice on prevention, treatment is based on evidenced. 'Doing PPI' for the sake of PPI just doesn't do it for me.  

I want to see research that has the needs of patients at its heart. I want to know that researchers have actively sought the advice of patients and carers to consider relevance and practicality of the study. I want study participants to be told about the results. I would like the subsequent application of that research used effectively across the NHS.

The irresponsible misuse of 'doing PPI' makes it almost impossible to create and develop a climate of change. It has become an end-product rather than the process of focussing on improving research or delivering better services.

The danger of this, still too prevalent, product based approach is that the reporting on such 'activity' records the input rather than any output. Xx number of meetings, Yy people attended, Zz committee members - rather than the actual purpose, the impact and the benefit.

The threat is that the horizon is limited to people attending meetings or being a representative on committees. The challenge is to provide those people with a clearer definition of role. Simon Denegri is demonstrating on his Lay Review how people are making a difference and providing information and comment that is about the purpose of change. 

The greatest risk is that it wastes the time that could produce change.

I have contributed to the fight to achieve 'presence' at meetings, in committees and on boards. The purpose was never just to be present - it was to foster change in culture, climate and commitment to placing the patient at the heart of change.

Policies, strategies, plans and toolkits about involving the public, carers and patients abound in profusion on shelves, in filing cabinets and even in my loft but too many of these focus on the product of involvement. The guidance in almost all of these documents is about how to do PPI. It is more of the same 'doing PPI'. 

It is not and never should be about PPI. 

It is about change, development and improvement. It is as much about people as it is about reforming systems and structures. It is a continual process of learning rather than an end-product. As a learning process it needs to identify areas of need/concern, clarify the requirement for involvement and then properly assess whether there has been any  impact, benefit and change. It is too easy to have very good PPI where nothing changes.

My advice is quite simple - SPELL IT OUT! Let's get rid of the accursed letters and...

SPELL it Out! Spell the whole statement and start with "Involving..." or "By involving..." 
Do NOT use the letters on their own.

Spell IT Out! Focus on the IT. What is involvement of people doing, about to do or has done. "By involving patients in this we did Xxxxx", "by talking to people who care for patients with Xxxxxx we learned ...." "In a short survey carried out in a local supermarket, members of the public clearly stated that they had ..... "
Do NOT write we are doing PPI.

Spell it OUT - Call what you are doing 'Changing Services, Improving Care or A Focus for Development' with a separate strap line - citizens in research or by participation, involvement and engagement. 
Do NOT call it a PPI Strategy, Policy, Plan, etc

So, when you next see those letters, use a red pen. When you hear them ask "What is the purpose? Try not to touch them with a......BP (Barge Pole).

My particular interest is about the value of research as a means of improving healthcare. This interest has become a passion driven by those who like myself have been touched by a life threatening illness and also by the huge numbers of dedicated and committed research professionals who share the same purpose.

I believe that the time is right to begin a new dialogue about our health services, about working together in ways that gain from each other's knowledge, skills and experiences. This is partnership working and not involvement.

And if you are still not convinced than type PPI into an Internet search engine and you will get Payment Protection Insurance (PPI) or Polly Peck International (PPI). Need I say more?


The time seems right for an honest and robust discussion about whether placing two people on a committee is necessarily the most appropriate tactic. How do we best gain insight from experience? Has some involvement been too much about 'us' becoming 'them'? How do we create change?

I will soon be tweeting about Improving Research by 'Moving Beyond Presence' through the creation of dialogues, working together, shared decision making and co-production.