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

Calendar Watching

Calendar Watching

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?