Pernicious Anaemia Society
Eighteen months ago I submitted a re-evaluation request to the BNF asking them to look again at the treatment of Pernicious Anaemia. The frequency of replacement therapy injections remains the single most common cause of complaint to the PA Society. The re-evaluation was carried out, which involved a thorough investigation into any new research that had taken place around the treatment of PA (none was identified because no research had taken place), and the issue was then debated by a committee of the BNF which included my comments relating to the problem with some, though not all patients having problems getting a treatment regimen that is based on their individual needs. Because no new evidence in the form of published papers existed the committee deemed it unnecessary to issue an update on the treatment.
Friday’s meeting was the first opportunity for me to put the case for a review on a face to face basis.
The meeting was amicable and not unproductive. It was put to me that unless I could provide the organisation with evidence that some people need more frequent injections than others then the guidelines (and it was pointed out to me that they were just that – guidelines) would remain as they were. It was made clear to me that, just like other aspects of healthcare, the guidelines for treating patients with whatever disease have to be based on scientific evidence not least because of the risk of any litigation claims. That is why it is so important that we get started on the research that is already planned and financed into why patients’ needs vary.
There was one glimmer of hope, however. I was told that if I can provide evidence that some doctors are prepared to treat the patient according to their individual needs then the wording of the current guidelines could be changed to include something like “the treatment can be varied according to the need of the individual patient”. Again, it’s back to providing the evidence which is what I will now work on.
Here we go again – another sad tale. I took a telephone call on Friday. It was from a member who had joined a few years ago on behalf of her mother who had been diagnosed with Pernicious Anaemia.
“I just thought you’d like to know that my mother is in hospital. She is in her 80s and has been stumbling around for a few months and last week she fell and broke both of her arms.
“I went with her to the hospital and one of the hospital doctors was examining her and asked if she had any medical condition. She replied that she had Pernicious Anaemia. The doctor asked when she had her last injection. She told him it was last given eighteen months ago. I was shocked. I asked my mother why they had stopped her injections and she said she didn’t know why just that when she went for her three-monthly injection the nurse said that the doctor said she didn’t need them any more.
“What can I do”?
I told her that I would write to the medical director of the Clinical Commissioning Group.
Then, ten minutes later I had another call. It was from the lady I had been successful with in getting her injections re-instated after I had written to the Medical Director of her CCG.
“They’ve stopped my injections again” she told me………
It was on my birthday (September 3rd) that a news story broke that especially caught my attention. Scientists from Bristol University had discovered how to ‘switch off’ the gene that causes various auto-immune conditions including Multiple Sclerosis and type A Diabetes.
Now, fully fledged and full-blown Pernicious Anaemia is of course an auto-immune disease and so I immediately contacted the lead scientist of the Bristol project who is Prof. David Wraith. Professor Wraith invited me to visit him which I did on Tuesday of this week (2nd November). It was a very productive meeting. I explained that all that the Pernicious Anaemia Society could do to change the way in which we are diagnosed and treated is to ‘raise awareness’ among medical professionals of the problems we face in getting diagnosed quickly and treated adequately. I explained about the new British Committee for Standards in Haematology (BCSH) Guidelines and that now the society’s focus was to concentrate on getting members of the society treated according to their individual needs.
“Well you are certainly doing a good job in raising awareness” David told me; “I hadn’t even considered Pernicious Anaemia as being part of the study and of course it is much more common than other diseases that we are looking at”.
My trip down the M4 had obviously paid off.
I’ve every reason to believe that Professor Wraith and his team will be successful in their task in what is a very complicated part of medicine. And, for the first time, there is hope that patients with Pernicious Anaemia will not only have their illness treated, but it could also be cured.
The diagram on the right is a heat map of genetic things – whatever that means – as I said, it’s extremely complicated!
Well the busy two weeks is nearly over. This past week I have been to London and back three times on three consecutive days (London Hotels are prohibitively expensive) and overall it has been worth it.
I would like to report that my meetings with the Royal College of Pathologists, Medical and Healthcare Products Regulations Agency and the Department of Health were a resounding success and that things would now change. Unfortunately I cannot, but I can tell you that I have raised awareness among some serious players in healthcare in the UK of the problems faced by members of the PA Society and not only that, have been pointed in the right direction to get things changed.
I have one meeting left in this present round of campaigning – with the Director of the British National Formulary in November, but following the meetings that have taken place I now realise that unless there is some robust scientific evidence available that proves some patients need more frequent injections than others I will be going around in circles.
All is not lost. We have three research proposals in the pipeline and it is only a matter of time until we do get the evidence that is needed. And so, for the next year I will be encouraging the doctors and scientists who are working with us to carry on with their work. We can do a lot to facilitate this research and we will be applying for further grants to enable this to happen. It will take time but I am now convinced that until we get that evidence that has been peer reviewed and subject to scrutiny any efforts to bring about change will prove futile. Back to the drawing board it is!
Tomorrow is the start of a round of meetings that will centre on getting the way Pernicious Anaemia is treated changed. I am in London meeting with the Royal College of Pathologists and on Thursday I am back in London for a meeting with the Head of Self-medication and one of her colleagues at the Medicines and Healthcare products Regulatory Agency (MHRA). Next month a meeting has been arranged with the Director of the British National Formulary (BNF) and one of her colleagues.
What do I hope to achieve from these meetings? Well I cannot request that the current treatment regimen be changed. That is now what I can do. As a representative of a patient support group (of over 10,000 members) the only thing that I can be justified in doing is raising awareness of the problems encountered by our members. And here’s some statistics from our paper published in April that was the result of an analysis of our survey of nearly 1,500 members:
64% of patients with Pernicious Anaemia are Unhappy with their treatment
Words Used By Patients to Best Describe Their Care:
Very Poor (20%),
Very Good (7%),
I have to be at the meeting tomorrow at 10am and so it’s a 4:30 start for me. I will let you all know the outcomes of the meetings – fingers crossed.
It started off with an all too common telephone call. “I’m nearly 80″ he told me. “I was diagnosed last month with Pernicious Anaemia. I’m so tired all of the time and I have dreadful pins and needles in my hands and feet”.
I asked if he was feeling any improvement from the injections.
“I’m not having any” he told me. I asked why on earth not?
“Well the senior partner told the junior partner at the practice that I was nearly 80 so what could I expect?”
This was a first – a patient with all of the neurological symptoms and a firm diagnosis of Pernicious Anaemia and there was no treatment being given because this was to be expected due to his age. And then the telephone made a series of beeping noises which indicate that there is another incoming call – a ‘call waiting’. I decided to ignore the incoming call and advised the elderly gentleman to make an urgent appointment to see his doctor and tell him that he had spoken to us and that we were extremely concerned about his lack of treatment and that if he doesn’t receive loading doses immediately then I will write to the Clinical Director of the NHS Trust concerned. I also told the patient that if he still doesn’t get any treatment then he must ask his doctor to put in writing why treatment was being withheld.
His reaction was the same as if I had given him a million pounds – he thanked me profusely and told me I should be made a saint. I didn’t disagree.
So then I checked on the ‘missed call’ list on the phone and dialled the number. At the other end a voice spoke. “Hi Martyn, it’s J*****” (I’ll withhold her name for confidentiality reasons). This was one of, if not the most senior adviser to the Dept. of Health in the UK. I had met her once before.
I apologised for not taking her call and related the story of the elderly man. “You can make a formal complaint on his behalf” she said. I told her that if I did that to every call I wouldn’t be able to do anything else. She was quite shocked.
Anyway, the fact is that she wants my help in disseminating the new Guidelines from the BCSH to GPs – something I am delighted to be involved in. I don’t want to go any further but I must say the way in which she plans to do this is very clever and will reward GPs who read and digest the new guidelines with Continuous Professional Development (CPD) credits. So whereas I thought I would be having a quiet weekend I will be burying myself in the new guidelines again.
Why did she ask me to be involved? Because we know better than anyone else what problems need to be addressed. And if I start to get frustrated and tired in this next little project I will simply remember the telephone conversation with an 80 year old man who is being left untreated; and we all know what happens when PA is left untreated – it becomes pernicious.
So far this week I have received three responses to the letters that I sent two weeks ago (see my post – Campaign for Better Treatment Begins).
I received a letter on Tuesday from the Chairman of the British Medical Association’s Council that stated that my concerns had been forwarded to the specialist committee that deals with all matters linked to the British National Formulary.
Yesterday I received an email that contained a letter from the Minister for Health for Wales – Mark Drakeford AM who stated:
“the management of pernicious anaemia would be a matter for the patient’s clinician to decide, in consultation with the patient. Together, they should discuss and agree what treatment would be most appropriate to meet the patient’s individual needs and agree an individual treatment plan” – going quite well isn’t it? But the end of the sentence speaks louder than the rest:
“that best reflect latest clinical evidence”. And, you see, there isn’t that evidence or rather there is, but it’s not codified in one single document.
Another response was from the chairman of the Medicines and Healthcare products Regulatory Agency – MHRA stating that he is arranging a meeting between me and the Head of Patient Self Care.
So, things are moving, but very slowly. And then there was that amazing telephone call – see the post above!
As I have said previously, for the past six years there have been two main objectives of the Pernicious Anaemia Society: the first was to get the way PA is diagnosed thoroughly reviewed and, though it wasn’t as thorough as some people would have wanted, the Updated Guidelines by the British Committee for Standards in Haematology that was published earlier this year goes a long way to achieving this. Now we are concentrating on the second objective which is to “allow patients a choice of replacement therapy treatment including delivery method and
frequency of delivery”.
There are, however, a number of major problems to overcome in order to achieve this objective. And the first one relates back to the new guidelines mentioned above. The Guidelines for Cobalamin and Folate Deficiency does not address the most common cause of complaint by members of the Pernicious Anaemia Society if not all patients which is that many of our members are unable to receive replacement therapy injections based on their need but are given what is probably the lowest denominator ( The most basic, least sophisticated level of taste, sensibility, or opinion among a group of people – The Free Dictionary) for treatment. The guidelines do nothing to address this problem other than referring the way in which treatment is prescribed to the British National Formulary (BNF) which publishes twice a year the handbook for doctors telling them how to treat and prescribe diseases and illnesses. The BNF states that treatment for Pernicious Anaemia is a 1mg/ml injection of Hydroxocobalamin every twelve weeks except where there is neurological involvement where the treatment is an injection every other day until there is no further improvement (the new guidelines state that it is difficult to justify allowing this treatment to go on further than three weeks and so the next edition of the BNF will probably take this into account). So, in order that patients can get treated according to their own individual requirement and by using a delivery method of their choice it is easy to see that all that is needed is for the society to contact the BNF and tell them that the current treatment method is often inadequate and causes unnecessary suffering that impacts on the patients work commitments and family life etc etc. Oh! that it would be that simple. Almost immediately it became apparent that this was not going to be an easy task. The BNF you see, is not a single enterprise but a joint publication by the British Medical Association and the Royal Society of Pharmacists – and it doesn’t stop there.
It begins with a review of developments in the past six months (the publication is updated twice a year) and that review begins with taking a look at recent developments. As the BNF website puts it “Information on drugs is drawn from the manufacturers’ product literature, medical and pharmaceutical literature, UK health departments, regulatory authorities, and professional bodies.”
And there is some cause for optimism because – “Information in BNF publications has been validated against emerging evidence, best-practice guidelines, and advice from a network of clinical experts”. I like the bit about ‘emerging evidence’ which provides a gateway for the society to provide the editors about the growing use of Methylcobalamin as replacement therapy (10% of those who completed our survey used this unlicensed form of B12).
The Editorial Team is made up of a number of Clinical Writers and each Clinical Writer is responsible for editing and updating specific chapters of the BNF and the BNF for Children (I’m just going to concentrate on the BNF for the time being though in time we will have to get involved with the Children’s edition). The Clinical Writers have to be convinced that any new information comes from a trustworthy source and is “reliable and relevant”. And so I will now assemble what evidence there is from reliable and relevant sources that some patients respond better to one form of B12 than another. The critical issue on any evidence that I might submit is that it has to be reliable and relevant which cannot be anecdotal evidence. This is going to be an issue but one that I will work on.
Any newly drafted section is then sent to the Joint Formulary Committee (JFC) and it is the JFC that decides on “matters of policy and reviews amendments to the BNF in the light of new evidence and expert advice” – my italics. So what “new evidence” do we have? Well, we have our survey results which were published earlier this year, and we also have other papers showing that some people show marked improvements in symptoms when Methylcobalamin is administered. As to the “expert advice” – well, over the years we have established relationships with a team of highly respected doctors and scientists who I’m sure will be pleased to be involved in our campaign. You may be wondering how this evidence and advice can be submitted to the BNF and I suppose it all points to a Review or Report. However, I’m still unsure which is why I have written 18 letters this week to the Presidents and Chairs of all those associated with the BNF – see below.
According to the BNF website the composition of the JFC “includes doctors appointed by the BMJ Group, pharmacists appointed by the Royal Pharmaceutical Society, and representatives from the Medicines and Healthcare products Regulatory Agency (MHRA), the UK Health Departments, and a national guideline producer”. And it is to the heads of all of these agencies and organisations that the letters mentioned above have been sent simply to get the ball rolling so to speak.
So once debated by the JFC the proposals are then sent to a team of “expert advisers” – and there are over a hundred of them made up of doctors, nurses, pharmacists and dentists. The role of these expert advisers is to:
“ensure that BNF publications remain reliable by:
- commenting on the relevance of the text in the context of best clinical practice in the UK;
- checking draft amendments for appropriate interpretation of any new evidence;
- providing expert opinion in areas of controversy or when reliable evidence is lacking;
- advising on areas where BNF publications diverge from summaries of product characteristics;
- providing independent advice on drug interactions, prescribing in hepatic impairment, renal impairment, pregnancy, breast-feeding, children, the elderly, palliative care, and the emergency treatment of poisoning.
Just how many of these advisers will be aware of the alternative B12 treatments available is not known but I take heart in the following:
“In addition to consulting with regular advisers, BNF publications call on other clinical specialists for specific developments when particular expertise is required”. So if our suggestions are taken seriously and get to this stage hopefully we will be asked to identify an expert who will be able to comment – and we do know some reliable experts who would gladly get involved.
There are other Sources of Information that feeds into the BNF as well as Expert Advisers. These include:
Summaries of Product Characteristics (SPC). These are what their name says – summaries of the characteristics of all new or revised products – or as the website puts it the BNF “receive summaries of product characteristics (SPCs) of all new products as well as revised SPCs for existing products” Now, ask yourself if you consider Methylcobalamin to be a ‘new’ or ‘revised’ product? Are nasal sprays, sub-lingual drops, skin patches ‘new’ or ‘revised’ forms of B12? And you should ask this because what the JFC people will specifically doing is “comparing the indications, cautions, contra-indications, and side-effects with similar existing drugs. Where these are different from the expected pattern, justification is sought for their inclusion or exclusion”; in other words will the Methylcobalamin compare favourably with the already prescribed hydroxocobalamin and cyanocobalamin? They will also be “identifying potential clinical problems or omissions and seeking further information from manufacturers or from expert advisers; “and constructing, with the help of expert advisers, a comment on the role of the drug in the context of similar drugs”.
As well as the Experts and SPCs other sources of information used by the BNF include:
Literature. Clinical writers monitor core medical and pharmaceutical journals.
Systematic reviews. BNF Publications has access to various databases of systematic reviews (including the Cochrane Library and various web-based resources).
Consensus guidelines. The advice in BNF publications is checked against consensus guidelines produced by expert bodies including NICE.
Reference sources. Textbooks and reference sources are used to provide background information for the review of existing text or for the construction of new text including Martindale the complete drug reference.
Statutory information. The BNF routinely processes relevant information from various Government bodies including the British Pharmacopoeia Commission, the Commission on Human Medicines (CHM) and UK Health Departments. I’ve written to the CHM and all UK Health Ministers. And we’ve got the petition on the Government’s website to raise awareness.
Pricing information from the NHS Business Services Authority.
Comments from readers. Readers of BNF publications are invited to send in comments. Numerous letters and emails are received by the BNF team. Now, I’ve never read the BNF though I have studied on or two individual pages so I’m not a “reader” but I have sent a letter in to them. And I’ve sent them two emails.
Comments from industry.
Virtual user groups made up of doctors, nurses and pharmacists
Market research. Market research is conducted at regular intervals to gather feedback on specific areas of development – and I hope they ask us!
Is all of this scrutiny necessary? Is it vital that all of these different organisations and individuals need to be involved?
Of course it is – these people sanction some pretty dangerous preparations that are quite rightly subject to such thorough investigation. Whether these same rigorous standards should be applied to a harmless vitamin is a matter for you to decide – as far as I’m concerned I’m quite pleased that these people do what they do. If I am going to inject something into me I want to know it is safe. There is no alternative to the process – there are easier alternatives but I prefer to be safe rather than sorry.
So, that is the mountain we will have to climb in order to achieve our next objective – that patients be given a choice of treatment and that treatment is based on the individual’s requirement.
Who’s up for it?
A few weeks back I wrote about a large conference on Folic Acid and B12 taking place in Steamboat Springs, Colorado, USA.
Yesterday I met with one of the British attendees for an update on the outcome of the conference.
I was expecting some positive results – the triumph of optimism over experience.
The conference was hugely successful, not for solving any of the problems with B12 and Folic Acid, but for new, previously unknown
discoveries being presented for the first time.
Central to the whole problem in determining healthy levels of B12 is the issues of analogues. Analogues are a mystery and although they are known to interfere with producing an accurate picture of the B12 status in people. Analogues ‘mimic’ or ‘impersonate’ B12. This is known. What isn’t known is really fundamental to understanding their effect on determining B12 status – nobody knows what they are.
Take Seaweed, Dulce or Tangle as it’s known (because it tangles around everything – cute eh?) is known to contain not only large amounts of iodine (it smells like some nurses) but also high levels of Vitamin B12. So, all you vegetarians out there need only eat some seaweed in some form – dried, boiled or raw- and you’ll get all the B12 you need correct? Wrong- the B12 in seaweed is an analogue of B12 and won’t do you any good.
It’s so reassuring that there are international conferences being held that are being attended by some very clever people all dedicating their working lives to trying to understand the nature of B12 (and folic acid), but it seems there is still a very long way to go before this dedicated school of scientists find the answer to the difficult questions they ask. Different people, it appears, have very different analogues of B12.
And the emerging sciences? Keep your eye on developments in Epigenomics and I’ll leave it at that.
It’s often easy to forget the difference we make in the day to day lives of members. I’ve just received this from a member who I telephoned earlier on in the week.
Just a quick thank you note to Martyn. You phoned me two days ago when I said I was on cyanocobalamin instead of hydroxocobalamin. I took your advice and visited my GPs practice. A different doctor said immediately I was on the wrong cobalamin, apologised, and said she would talk to the other doctor. She injected me there and then, and set up another series of injections.
Interestingly, she also said that the new guidelines In Scotland are for an injection every 10-12 weeks, so things are moving away from the inflexible 12 week period and in the right direction!
We’ll keep on doing what we do!