Overdiagnosis and industry influence: how cow’s milk protein allergy is extending the reach of infant formula manufacturers
BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k5056 (Published 05 December 2018) Cite this as: BMJ 2018;363:k5056Read all The BMJ's investigations
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
As a GP many of the parents I see with concerns have been sent and 'informed' by their health visitors.
Who educates the health visitors on their knowledge, application and impact potential? They are likely to be acting on 'the national guidance', unaware of its pitfalls and the subsequent compromised position the GP who next sees this parent and child finds themselves in.
As one of the GPs quoted in the article put it, “Virtually every single infant could potentially be diagnosed using these symptoms.” I couldn't agree more.
We need to include the whole of the community care system who deal with infants if we want to make some impact on this new 'health concern for parents', this pharmaceutical epidemic, this unnecessary un-affordable drain on NHS funds.
Competing interests: No competing interests
Chris van Tulleken’s investigation (1) in to the potential overdiagnosis and industry influence of cow’s milk protein allergy (CMPA) in infancy is both overdue and welcome. His paper has already started to share this dirty secret through the reporting in the press at the time of publication (2). It should embarrass the NHS, the Royal College of Paediatrics and Child Health (RCPCH), several other clinical associations and some of the established experts. It should lead to penetrating introspection and deep ethical consideration across the field.
Firstly, non-IgE mediated CMPA is a clinical diagnosis backed up by an empirical test (does the infant’s symptom profile improve after changing the feed and omitting the presumed allergen?). Regrettably there is no sensitive, specific or reproducible test to objectively confirm the diagnosis and as this paper neatly clarifies the symptoms are often vague and common.
Maternal dietary change can help a genuine case of CMPA in an exclusively breastfed infant. However, the situation is more complex in the already formula fed child. Given that a hydrolysed or amino acid based milk substitute is prescribed by a doctor, it is free of charge to parents from the UK NHS. Rapidly, a situation evolves where it pays the parent to continue using the specially prescribed milk substitute. Unless the infant either refuses the feed, or is somehow worse on this alternative feed, the parent may, quite understandably, be persuaded to continue an unnecessary treatment which is expensive to the NHS. This saves much money for the parents whether, or not, there is actually any clinical benefit at all.
We urgently require independent, properly designed randomized control trials to help clarify the value of this intervention particularly when the symptom profile is vague and less obvious. This has already been recognized by NICE (3). We also need a concerted effort to establish diagnostic tests that do not rely on the treatment itself.
Secondly, in respect of conflicting interests the paper makes important observations and reports defensive quotations from experts in the field. Interestingly, while there is silence from the current President of the RCPCH (1), the December 2018 issue of the Archives of Disease in Childhood has a prominent advert for an amino acid based feed used in the treatment of CMPA. As is the norm, this particular promotional advert (4) has a picture of a perfectly content, handsome baby next to apparently scientifically sound headlines aimed at offering a degree of clinical and research credibility. This hidden persuader is cleverly placed on the page adjacent to the journal index, which every reader is likely to read and then receive a subconscious reminder of the advert’s message.
The industries that manufacture these products largely fund paediatric CPD, significantly fund the RCPCH and also fund our specialist societies. They pay handsome speaker fees to colleagues who regularly publish on the topic and to those who prescribe or influence prescription of these expensive milk substitutes. They pay the conference fees, arrange the travel and cover luxury hospitality for colleagues to attend scientific meetings around the world. This contribution represents very large sums of money and saves busy clinicians the hassle of booking flights, coordinating transport, searching hotels and even finding food while away. I know this having benefited in the early part of my consultant career from such generous hospitality.
I feel that financial declarations of interest must be; mandatory, honest, published, widely available to the public and completely transparent. This process should include all health professionals. It should cover all close family members and must also refer to the indirect hidden benefits we continue to enjoy even when, like me, you have been apparently clean for several years.
Finally, these are all my current declarations; no sponsorship or direct benefit to me since 2011, my wife (pharmacist) has been paid for consultancy by Jazz, Janssen and Takeda within the last 3 years, I am a member of the RCPCH, I Chaired the BSPGHAN Endoscopy Working Group 2012-2015 and was Chair of the GDG for NICE NG1 2015. I still benefit through attending and receiving hospitality (as a speaker) at events organized by associations that are supported by multiple industry sponsors including the manufacturers discussed in the paper.
References
1. van Tulleken. Overdiagnosis and industry influence: how cow’s milk protein allergy is extending the reach of infant formula manufacturers. BMJ 2018;363:k5056
2. Infant milk allergy rate soars as investigation finds senior child doctors have extensive industry links https://www.telegraph.co.uk/news/2018/12/05/infant-milk-allergy-rate-soa...
3. NICE NG1 2015 https://www.nice.org.uk/guidance/ng1/chapter/2-Research-recommendations
4. New Neocate Syneo. Arch Dis Child Dec 2018 Vol 103 No 12 (inside the front cover)
Competing interests: These are all my current declarations; no sponsorship or direct benefit to me since 2011, my wife (pharmacist) has been paid for consultancy by Jazz, Janssen and Takeda, I am a member of the RCPCH, I Chaired the BSPGHAN Endoscopy Working Group 2012-2015 and was Chair of the GDG for NICE NG1 2015. I still benefit through attending and receiving hospitality (as a speaker) at events organized by associations that are supported by multiple industry sponsors including the manufacturers discussed in the paper.
I agree with many of Dr van Tulleken's highlighted concerns, but they merit some qualification. Colleagues have commented to me that many academic meetings are dependent on industry support; and paediatrics doesn't have the diversity of different pharmaceutical companies creating a balanced 'pharma-biome' in which to culture healthy relationships. That being said, I'd qualify the article to say that removing CMP from the diet is highly effective in certain situations (e.g. blood in the stool). I think it highlights the importance of integrating guidelines so they say the same message e.g. NICE food allergy, and GORD in children (NG1) and constipation (CG99 - neither are mentioned in the article) and having a corpus of guidance, rather than free-standing guidelines which may be more prone to being influenced.
I note the absence of voices (either patient or clinician) taken from outside the M25. In the absence of a definitive test, and a burden of disease, the importance of maintaining parental confidence in breastfeeding even if on a CMP free diet, walking that difficult journey with parents, and supporting their choices with information is key: within the multidisciplinary team (including health visitors and dieticians). These families rarely have 1 symptom in isolation, (e.g. reflux+family history of CMP+eczema) for clinicians to start off with an exclusion diet and you'll be able to give families an idea of how likely an exclusion diet will work (e.g. only 10% patients benefit from an exclusion diet in isolated constipation).
I hope that reflects the pragmatic approach taken outside certain specialist centres, and the efforts we take in improving parental confidence.
Competing interests: NICE fellow and contributor to NG1: NIGE guidelines for GORD in children
This article and accompanying editorial on the overdiagnosis of CMPA rightly identifies a growing issue. One factor not mentioned is that the extensively-hydrolysed or amino-acid based formula milk often used in the management of CMPA are only available via prescription, which is course makes them free to infants in the UK.
CMPA can be difficult to diagnose with symptoms overlapping other conditions such as gastro-oesophageal reflux disease and infantile colic, and therefore a change in milk can be trialed with subsequent assessment of response based in part on parental feedback. Given a diagnosis of CMPA will save parents of formula-fed babies the expense of buying milk, estimated between £28 and £97 per month (1), there is a significant conflict of interest which could well be contributing to the increasing diagnoses.
1 – Costs of infant milks marketed in the UK, Published February 2017 by First Steps Nutrition Trust. Accessed online on 10/12/18 https://nhsforthvalley.com/wp-content/uploads/2014/03/Costs_of_Infant_Mi...
Competing interests: No competing interests
This article describes massive conflicting interests at the heart of our scientific evidence base. Early NICE guidance used to grade each statement according to the strength of evidence supporting it. Perhaps this explicit grading could be brought back, with a new grade added to emphasise statements potentially based on corrupted opinion.
Competing interests: No competing interests
Speaking as a mum and a GP with a cows milk intolerant baby I was shocked to find the vast majority of information on cows milk protein intolerence on the web is industry sponsored . That also has a lot to do with financial with Influences over optimisation on a google search .
I would have loved to breastfeed but had to bottle feed . I found it was difficult to convince a gp to give me extensively hydrolysed formula for my 8 week old baby who had colic and such frequent stools he was taking double the normal amount of formula to maintain his growth . I stood my ground as he was starting to get flushing and facial swelling at feed time. Within 48 hrs he was a happy thriving colic free baby taking 5 bottles a day instead of 10 . As a bonus his very mild eczema vanished , his mild reflux stopped and his cot sheets were no longer drenched in the morning.
In the community there is still cynicism that mums only want 'free milk’. Only someone who has not used EHF would say that . Normal formula instructions are inconvenient , EHF Smells bad and does not come ready made , mums that are not convinced of benefit will rarely persist . Those whose babies respond rapidly to a trial of EHF will refuse to re-try normal formula . Prescriptions have gone up as it is easier to prescribe , they needed to to some degree .
What is most sad is the number of mums who have given up breastfeeding to bottle feed by the 6 weeks check through lack of practical support for breastfeeding in the early weeks or never started for social reasons .
Competing interests: No competing interests
The somewhat misleading RCPCH response does not address the key issue.
On-going RCPCH entangelment with formula manufacturers, justified by focussing on the promotion of so-called "specialist formulas", allows the companies to circumvent Unicef UK BFI standards on access to clinicians and enhances the company brand by association. Formula advertisements are placed prominently at conferences (including the annual RCPCH meeting) or on a full page or a back cover of a journal (including the RCPCH journal), and can achieve broad brand recognition and credibility by association with a respected professional organisation.
Competing interests: No competing interests
The RCPCH wishes to correct the below statement, which is inaccurate:
"The RCPCH accepts funding from Danone and Nestlé, two of the largest formula manufacturers, but according to its website it will only accept advertising or conference stands providing information about specialist formulas, not breastmilk substitutes."
The RCPCH due diligence policy states that any sponsorship or presence at our annual conference or events will only involve specialist formulas. Specialist formulas are breast milk substitutes. We acknowledge that this could be better clarified on our website, and we will do so to state that we will not accept advertising or conference stands promoting standard breast milk substitutes.
In relation to education and research projects, our policy states that there will be no involvement by the donor in the selection of topics, choice of speakers, programme content, or actual spend of funds.
In order for the RCPCH to accept funding, organisations must meet relevant Codes of Practice or show demonstrable commitment to working towards meeting them and demonstrate willingness to share information on breaches of the relevant Codes, including violations of the International Code of Marketing of Breastmilk Substitutes. Organisations must also provide a reasonable explanation should any inconsistencies be identified between information provided by them and information obtained by the RCPCH. Specialist formulas are not exempt from the WHO code, but contact with “non-state actors’ (in this case the formula milk industry) is permissible under the 2016 amendment to the Code.
The RCPCH consulted with members about the College’s relationship with Formula Milk Companies (FMCs) in 2016. The vast majority of respondents said they felt the RCPCH should accept funding from FMCs and allow them to advertise at conferences and events – but only with a robust set of safeguards in place.
Over the last year, we’ve been working with the major FMCs, and so far Danone and Nestle have met the due diligence criteria. The procedures and policies of both companies will continued to be reviewed by the RCPCH, as will our work with them to further improve the marketing of their infant formula milk products. Discussions will continue with the other companies who are yet to meet our due diligence criteria.
Competing interests: No competing interests
Re: Overdiagnosis and industry influence: how cow’s milk protein allergy is extending the reach of infant formula manufacturers
N Saghir, J Stallard, R Saghir, U Anwar
Burns and Plastic Surgery Department, Pinderfields Hospital, Wakefield
We commend the recent work by Chris van Tulleken highlighting the impact that formula manufactures have on the medical profession and mothers. We agree with Bob Klaber that they have significant influence over mothers and their children at the most vulnerable time in their lives.
There needs to be a vast change in the way the medical profession interact with these industries. Manufactures spend a large budget on marketing their products. We would like to take the opportunity to express the need for these leading manufacturers to allocate money to burns awareness. As a regional burns centre for children we regularly see patients with significant scald injuries secondary to formula preparation. On average we see two children a month.
We advocate the need for increased awareness on packaging; regarding safe formula preparation. We also feel the leading industries need to assist in increasing first aid knowledge amongst parents, so that if a burn was to occur, swift appropriate first aid is delivered, thus reducing the severity of injury. There is often confusion regarding appropriate first aid in presenting patients, regularly burns are not cooled for twenty minutes or dressed appropriately.
Competing interests: No competing interests