The biggest problem B12 deficient patients face once they’ve achieved a diagnosis is desperate under treatment. Our maintenance dose is listed in the NICE Guidelines ‘with neurological involvement’ at two monthly intervals and without at three monthly intervals. Unfortunately many doctors do not take into account neurological symptoms and the patient is automatically placed onto a three monthly maintenance dose of B12 injections after loading doses.

Vitamin B12 is water soluble. The rate of excretion is fast, there is no internal cupboard where we can pop a bit by for a rainy day. If we are lucky and our mother had a good supply of B12, we would be born with a store, but this eventually runs out or stops being accessible for many reasons.

Our maintenance dosage is based upon cost saving exercises and absolutely no care for the patient. Isn’t it time for a change in this old way of thinking?

The fact is that GP audits (and no clinical evidence or patient involvement of any kind) eventually made three monthly injections the ‘optimal’ maintenance dose of B12. These were purely designed to save money and had nothing to do with patient care, this situation needs an urgent overhaul.

It appears that without correct analysis, observation or consultation with patients many of our doctors truly believe we only need four injections a year because this is what has been repeatedly presented to them.

The content of these audits which I detail below, have become an intractable belief and have been cited by later research which then further eroded any good common sense. Worse still, other countries cite UK GP audits in order to back up rationed treatment for their patients too!

There would rightly, be an almighty uproar if every anaemic patient were told that they needed exactly the same amount of iron only 4 times per year, and all diabetic patients were told they need the same dose of insulin quarterly? Surely we’d think it crazy if it was suddenly decided that just 4 doses of vitamin C a year cured scurvy?

This post tries to detail how our three monthly injection regime was arrived at from  the first study and the following three GP audits.

Thank you for your email to BNF Publications. 

Unfortunately we are unable to access our archives to check what evidence base was used to determine the 3 monthly dosage of hydroxocobalamin. 

BNF content will be reviewed in line with the SPCs for future updates of the BNF.

• The first paper you see is from 1971 this discusses excessive prescription of B12 and seeks to ‘standardise B12 treatment’.  Like that would ever be appropriate!

• The next report in 1983 carried out in by a Leicester GP training practice. This decides that monthly B12 injections should move to ‘optimal’ 2 monthly frequency. It sets narrow and flawed diagnostic criteria and unfortunately set the tone for the following GP audits and it still largely influences diagnosis today.

• In 1985 a further study from Coventry was published titled ‘B12 injections: considerable source of work the district nurse’ this report tries to address the change from cyanocobalamin to hydroxocobalamin and just 2 years later decided that optimal B12 treatment is three monthly.

• The final audit took place in 1995 again in Leicestershire and this report used the same flawed diagnostic criteria and further reinforced the mad idea that humans only need vital B12 four times a year.

These repeated audits did not allow for GP’s to treat patients as individuals.

None of it is based on science or any clinical evidence – it’s based on pounds. The patients were dictated to, never consulted and neither were the nurses who administered B12 injections.

I have split this post into the four different reports and have highlighted extracts to demonstrate just how ridiculous and harmful they are;

First you will see a report from 1971 that in a study on excessive prescribing, B12 treatment was singled out, possibly due to the idea that GP’s were giving patients B12 injections, willy nilly as a ‘tonic’.

To see the full text follow this link – http://www.ncbi.nlm.nih.gov/pmc/articles/PMC478645/pdf/brjprevsmed00003-0029.pdf

I have chosen some parts to highlight below;

1971 Expected and Observed Values for the Prescription of vitamin B12 in England and Wales

A.L. Cochrane and F Moore M.R.C. Epidemiological Research Unit

(For your info – Epidemiology is the study of how often diseases occur in different groups of people and why. Epidemiological information is used to plan and evaluate strategies to prevent illness and as a guide to the management of patients in whom disease has already developed. – I add this meaning since the study below and the following audits, had the very opposite effect on preventing illness in B12 deficient patients.)

This report states;

There is considerable literature about the oddities of the prescribing habits of British doctors, the factors influencing them, and the attitudes of doctors to prescription, but there have been as far as we know, no attempts to compare quantitatively the expected amount prescribed, on the basis of good clinical practice, with that actually prescribed. There are in general three reasons for this ignorance of the prevalence of common diseases, the lack of specificity of particular drugs for particular diseases, and the lack of standardisation of therapy. Such a study requires a drug which is practically specific for one condition whose prevalence is known, and the one which approximates most closely to this appears to be vitamin B12. We should like to stress that B12 was selected for these purely epidemiological considerations and with no malice aforethought. This paper describes an attempt to measure the expected and observed values for the prescription of B12 in England and Wales for the year 1966.

Can we really expect that any B12 therapy can be totally standardised? Aren’t all humans different? Aren’t the severity and the variety of symptoms different in each patient? The length of time the ‘illness’ has progressed undetected surely would be taken into account if logic were applied?

Isn’t the statement ….’with no malice aforethought’ akin to saying I don’t wish to be rude, but….’

Why make a point of such a statement when the irony is that the whole study is designed to cut down on perceived (and not scientifically backed up) ‘excess’ treatment which served to harm patients and did not, by any stretch of the imagination – ‘prevent illness’?

Estimates for observed Prescriptions for parenteral B12

……It is clear that there is a considerable excess of observed over expected.

Reasons for Excessive prescription

a survey of the prescribing habits of a 2000 random sample of general practitioners in England and Wales in 1967 showed that 33% of all prescriptions for cyanocobalamin and hydroxocobalamin in 1967  were for conditions other than ‘pernicious anaemia and other hypochromic anaemias… 

Discussion

We are very conscious of the imperfections of our data……..We are also aware in retrospect that 1966 was not a good year to choose as it was a period of change in ideas about the correct dosage of B12 for pernicious anaemia……
………we still however believe our exercise to have been worthwhile as it has shown how substantial financial saving could be made at no cost to health and a considerable saving of inconvenience to patients, doctors, and nurses.

Is it really an inconvenience to the patient to have a life-saving injection at the correct frequency for them? We don’t think so. But of course by not giving injections money was indeed saved.

No B12 deficient patient wants to have more injections than they need, they simply want a frequency that keeps them well and completely able to function. It has always been a very small price to pay in the grand scheme of things. It would be an even smaller price to pay if;
a – patients were taught to self inject
b – we could buy injectable B12 OTC

This paper from 1983 focuses on pernicious anaemia rather than the many other causes of B12 deficiency, much like today, patients who do not have a definitive diagnosis of PA are considered to be in need of less treatment (or none at all) despite the severity of symptoms being exactly the same.

1983 BMJ Practice Observed Volume 287 –
Audit of the use of Vitamin B12 in general practice.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1549043/pdf/bmjcred00570-0031a.pdf

.……It has been shown that the observed use of vitamin B12 in general practice in England and Wales greatly exceeds its expected use and that it is widely prescribed by general practitioners for non-specific indications. Further evidence suggests the need to rationalise the use of vitamin be 12 in general practice.

…… The aims of the study were (1) To examine the present use of vitamin B12 in our practice and (2) To achieve a more appropriate and efficient use of it.

Method
……..The medical records (FP5,6) of all the patients were then reviewed to identify reasons for the use of B12 and the extent to which diagnostic criteria were established and appropriate management and follow up undertaken. ….. The results of the initial data collection were then presented to all the partners at a practice meeting. All the doctors agreed to change to the criteria identified by the authors, the practice nurses were advised accordingly, and a follow-up collection of data was undertaken.
In all cases where changes in treatment or management or both were introduced the patients received both written and verbal explanations from the practice doctors or nurses or both.

Note that the patients are not consulted they are just dictated to. I wouldn’t mind betting that some of the GP’s and nurses were concerned at this change in treatment being imposed upon them. Note that the nurses ‘were advised accordingly’ rather than being asked their professional opinion as the frontline workers.

Setting standards

In setting standards we decided that our criteria should be explicit – that is, identified before collecting evidence of performance – and that our criteria should be appropriate for British general practice, safe, realistic, and achievable.  In arriving at our criteria we consulted three standard textbooks of medicine (Alstead, Davidson and Price), a consultant haematologist, the librarian at the Royal College of General Practitioners, and the Monthly Index of Medical Specialities.

The following standards were set;

(1) Criteria for the use of vitamin B12–
(a) approved value in the treatment of pernicious anaemia only (other conditions are very rare in British general practice).
(b) May be necessary prophylacticly after surgery – four example gastrectomy, resection of the terminal ileum.

For all the good their method of ‘arriving at our criteria’ did for patients, they might just as well have consulted the butcher the baker and the candlestick maker. Note they didn’t consult a psychiatrist despite the link between low B12 and poor mental health being discovered over a hundred years ago.

This reduced regime did not make anything ‘safe’ for patients. In fact it served to  make the situation dire.

This intervention took away the GP’s chance to use deductive reasoning, to draw on experience of the past, to treat the person and not the ‘numbers’. It completely and firmly made treatment of B12 deficiency ‘one size fits all’ and woe betide anyone who does not toe the line. This is why the situation for patients still remains in a sorry state today.

As I said before PA is still thought to be the primary culprit here, other causes of B12 deficiency such as malabsorption caused by metformin, H2 blockers, PPI’s, parasites, etc. are completely ignored due to lack of knowledge.

The prevalence of PA against other causes of B12 deficiency these days is diminished. The genetic problems associated with B12 deficiency are not widely understood amongst health professionals despite their effect on a huge percentage of the population.

(2) Diagnostic criteria for pernicious anaemia–there must be
laboratory evidence of
(a) macrocytic anaemia;
(b) a low serum concentration of vitamin B12 with a normal folate concentration;
(c) a reticulocyte response to B12 treatment.

• All the criteria is based on blood values. We know that macrocytosis is a very, very late stage of B12 deficiency and that severely deficient patients may not present with this sign, the administration of folic acid also masks macrocytosis by normalising the size of the blood cells. Some GP’s still adhere to this criteria and NICE Guidelines bizarrely reinforce it for patients diagnosed with CFS and ME too. Quite ridiculous.

• Why on earth would any one with half a brain think that a high or a low folate concentration negates the need for B12 when the serum B12 level is low?

• We also know that the serum B12 test is inaccurate and cannot tell us what is happening at a cellular level. Using a serum B12 test in a patient on B12 injections to confirm ‘B12 levels are replete’ is incorrect, but it happens. Too many patients have their injections stopped because the doctor thinks they are cured once serum levels are above the low reference range. Unless the cause of B12 deficiency is temporary i.e. parasitic infestation which has been eradicated then treatment will be for life.

(3) Treatment and management Criteria – The optimum dosage is 1000 µg at intervals of eight weeks.

We need frequent B12 in order to keep brain and body healthy. For many patients today this frequency however, would be a miracle.

Results – (Be warned this is a tiny study!)
• 31 patients were in the study, 21 were women, 19 of them were over 65 years old.
• 22 patients (73%) were being treated for PA
• 5 were being treated post surgery.
• 1 for multiple sclerosis
• 2 for diabetes mellitus
• 1 for ‘no discernible reason’

In the interval between the two data collection dates 11 patients had died or left the practice, this included both patients with diabetes.

I wonder what these patients had recorded as cause of death? Of course we can’t know if this imposed reduced frequency had any impact however the word ‘pernicious’ springs to mind.

Vitamin B12 injections had been stopped for the patient with no discernible indications but the person with MS continued to have injections as she had become dependant on them.

Oh dear. Many severely deficient patients today would have ‘no discernible indications’ based on the sketchy criteria used in this survey and absolutely no comprehension of the ‘need’ of the MS patient, rather that she is ‘dependant on them’!

‘In all, in 17 patients injection frequency changed between the two surveys. 

Discussion

We make no claim to have identified definitive an immutable criteria for the use of vitamin B12 in general practice. We believe, however, that the standards that we set for ourselves are not only realistic and achievable but also reasonably reflect the current state of knowledge. We could discover no evidence to suggest that vitamin B12 having effective therapeutic role be on the correction of a specific or potential vitamin B12 deficiency state.

They certainly expected this criteria to be immutable though! The ‘current sate of knowledge‘ has moved on in 30 odd years and yet B12 ‘maintenance dose’ has since worsened.

…. A substantial and necessary reduction in the high number of injections of B12 administered to the patient was also brought about. The average number of injections per patient per year was almost halved 12.7-6.9 by greatly increasing the proportion of patients receiving injections at two monthly intervals 13%-84% the resulting savings in the cost of drugs and syringes, for example, are self evident and enabled nursing staff to devote the time saved to more important activities such as routine monitoring of patients blood pressures.

So this audit achieved its goal, life saving B12 injections were cut, at this point, from monthly to one injection every two months. They saved some cash on syringes and the nurses got to do ‘more important activities‘  – they did routine monitoring of blood pressure. Now I am no medic and although I know that monitoring blood pressure has its merit, but if we were to ask the simple question of ANYONE –‘What’s more important, is it (a) a routine blood pressure check or (b) a life saving injection? I think we can safely say the overwhelming answer would be (b).

In changing the frequency of the patient’s treatment regimens and we were conscious that we were disturbing what for many had become a regular part of their lives, often over many years. We had previously agreed that if any patient show distress at the prospect their current regimen should be continued. In the event no problems were encountered and no increase in consultation rates and ensued. This may have been due to the detailed explanations given to the patients, who were also reassured that no recorded instances of relapse had occurred in a two monthly schedule of injections.

‘No problems were encountered’ – ‘detailed explanations given to the patient’  I’d love to know what these detailed explanations involved. The problem is that patients don’t want to argue with doctors, they don’t want to challenge what they have been advised, they think ‘doctor knows best’.  The majority of patients may well have suffered in silence. REMEMBER there were only 20 patients alive at this point, probably barely alive and unable to cause problems!

Conclusion

… By collecting objective evidence of our use of vitamin B12 the differences between the medical care that we assumed we were providing and the care that we were actually providing we are made of this. This stimulated changes in Doctor behaviour and lead to improvements in our standards of clinical practice and patient care. Furthermore, all doctors agreed to follow the criteria identified in our future use of vitamin B12.

So the conclusion meant that the 2 monthly regime was solidified, the doctors who were previously prescribing to patient need, probably had their wrists slapped for not putting cost first. It also ‘fixed’ the terribly narrow diagnostic criteria.

Tragically this next audit published in 1985 only two years later, makes things a whole lot worse ; –

Putting money before health is a complete disgrace especially when, with a little lateral thinking, there was a perfect alternative solution to ‘the considerable source of work for the district nurse’ detailed below. Instead of teaching the patient/a family member to self treat they decided to just cut  the injection frequency and to hell with the consequences!

https://core.ac.uk/display/3914934

Vitamin B12 injections: considerable source of work for the district nurse 

It’s title should really be ‘arbitrary rationing of B12 injections’.

Abstract

Between June and September 1984, district nurses who worked in Coventry were asked to submit returns giving details of the patients for whom they administered vitamin B12 injections. Of 492 patients identified, 382 (78%) were receiving injections more frequently than the recommended three monthly dose of hydroxocobalamin. And extra 3751 injections were being administered a year. Four hundred and thirty (88%) of these patients have conditions for which the drug is a proven benefit, so the increased frequency of injections accounts for most of the observed excess. A total of 200o hours a year district nurse time is spent with these patients. The nursing services under increasing strain. Changes in vitamin B12 prescribing alone could make between 600 and 1470 hours available for other patient needs.

In the main this audit is trying to address the move from administration of monthly cyanocobalamin to three monthly hydroxocobalamin. Again there appears to be no clinical evidence for such bold statements.

This audit also uses the same flawed diagnostic criteria used in the Leicester study.

Introduction

…..Only a three monthly dose is needed.” It is therefore more convenient for the patient and cheaper by dosage regimen and in the time required of nursing staff to administer injections.

So now, just two years later we have moved to 3 monthly injections – WHY?!

In order to arrive at these treatment regimes you’d think they would have asked and recorded how hundreds of patients felt on this frankly, woefully inadequate level of B12 supplementation, but they didn’t.

Where exactly is the patient centred, solid, qualitative, peer-reviewed research from back when this ridiculously illogical idea originated? NOWHERE.

There is no proof that ‘optimal treatment’ for all UK patient’s is four B12 injections per year and there never will be. FACT.

This study below, published in 1967 carried out trials to determine how long cyanocobalamin and hydroxocobalamin B12 injections lasted before excretion in urine but you can see from their summary that it would be unreliable to assume that one size fits all.

Patient Variation in Pernicious Anaemia, as Shown in a Clinical Trial of Cyanocobalamin, Hydroxocobalamin and Cyanocobalamin–Zinc Tannate
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.1967.tb08734.x/abstract

 Variation between patients makes it impossible to anticipate the duration of effect of a single injection of one of these drugs in any patient.

B12 is a complex vitamin, it does amazing work in the body, but it can’t miraculously eek itself out over 3 months, it is excreted quickly as is the nature of all water soluble vitamins. This fact doesn’t change just because someone, somewhere wrote down that we only need four injections a year in an attempt to try to balance the books.

Psychological dependence is often mentioned as a reason for more frequent dosage. Fraser et al, however, reported no resistance by patients to reducing the frequency of their injections. Careful explanation was sufficient reassurance that there would be no untoward effects.

How patronising to dictate such a thing to patients. ‘Placebo’ or ‘somataform‘ are words often used when trying to persuade a patient that they have no need for B12 injections despite the fact they can’t walk or think or breathe without them.

Pressure on district nursing services in Coventry means that there is rationing by decreasing the time available to each patient and by longer patient waiting times. Optimising treatment should be a more acceptable means of rationing.

The word rationing tells us what is really going on here

Even if treatment for such conditions was given “ideally” the saving would be roughly only 18 hours per nurse a year. This is a small absolute amount for an initially understaffed group who cope with an expanding elderly population as well as the consequences of changes in hospital practice. Allied to other improvements in the use of the district nurse’s time it might contribute to appreciable savings.

Money Money Money.

This last paragraph was clearly not kept in mind when decisions on cost saving were made;

District nurses are respected and trusted members of the community health services. Their role in supporting elderly people in their own homes and in preventing handicap is largely undervalued -and unmeasured. Overall, costs for the population of patients in this study are about £18,000 a year. For patients with proven indications for vitamin B12 supplements this represents roughly £42 a year each. In times of high technology medicine and economic appraisal of health care this is a small cost indeed “to save a life.”

Remember – they state ‘proven indications’- based on flawed criteria used but the authors here know that B12 injections save lives. The fact is that the frequency of one injection every three months means that the quality of life for many patients is considerably compromised by gross under treatment.

These audits and no doubt countless associated studies, have encouraged GP’s to reduce the number of B12 injections and in some cases stop them altogether. This is harmful, but they think IT SAVES MONEY. Only it doesn’t really does it?

These patients who do not fit the criteria but who remain undiagnosed B12 deficient patients become very expensive for the NHS to look after. Without B12 supplementation, their deterioration may have meant and still means that they would be subjected to countless pricey investigations, scans and procedures, visits to psychiatrists, neurologists, gastroenterologists, and other ologists.

These audits NEVER advise that they will monitor and record the effect on the patient by asking how they feel – only that they may look at blood levels annually, odd isn’t it?

There may well be some patients who feel they do fine on 4 injections per year (or don’t want to say otherwise) – however those patients don’t write to me or join support groups. The point is we are all different. ONE SIZE FITS ALL cannot ever be possible in this situation?

A further nail in the coffin came in another later audit carried out in Leicestershire in 1995.

The message is clear – ‘you are giving too many patients B12 too often. Stop the patients who you don’t think need B12 from having it and those that may need it make them wait a few more weeks. If they whine give them some but tell them they don’t need it, it’s just that they have become dependent upon it’. In a nutshell this is how all the audits worked. They have successfully saved money and harmed patients with no basis of clinical evidence.

http://www.bmj.com/content/311/6996/28

General Practice
Use of vitamin B-12 in Leicestershire practices: a single topic audit led by a medical audit advisory group

I have highlighted key points below but to read full text please use the link above.

The specific aims were, firstly, to examine the use of vitamin B12 injections in all the Leicestershire practices; and, secondly, to achieve more appropriate and efficient use.

Criteria for treatment and management

• Optimum maintenance dose is 1000 µg at intervals of 12 weeks

• Follow-up annual blood count is required to avoid relapse

You see the obsession with blood values and yet no instruction to listen to patients, some of whom relapse only a matter of days post injection.

Results

…..There was a 32% reduction in the number of patients receiving B12 for non-valid reasons (from 521 to 352). 

….. This study is the most extensive assessment of the use of vitamin B12 in general practice yet reported. It has confirmed the findings are previously that B12 is still used inappropriately.

Nevertheless involvement in the audit stimulate a considerable change in behaviour among participating doctors, leading to subsequent improvement in their use of vitamin B12. For example the use of vitamin B12 for correct reasons improved by 10% (62% in phase 1 to 72% In phase 2) resulting in a 32% reduction in the number of patients inappropriately receiving it (521 to 352). Indeed some practices achieve dramatic change: One practice reduced the number of patients on B12 injections from 53 to just two…..

The proportion of patients receiving B12 injections at the correct frequency also increased by 14% (58% to 72%), which resulted in fewer patients receiving unnecessary injections.

Conclusion

……….It also provides further evidence that participation in audit can bring about change in clinical behaviour leading to improvements in standards of care

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230464/pdf/cmaj_161_2_146.pdf