Do hydrolysed infant formulas reduce the risk of allergic disease?
BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i1143 (Published 08 March 2016) Cite this as: BMJ 2016;352:i1143
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Thanks for your response to my previous comments. [1] You can only replicate a study if it actually took place in the first place. In this case, it is clear that the co-authors were surprised by the publication of studies for patients that they never saw recruited. The affiliated university clearly concluded in a report that was previously not known to the public that scientific misconduct had been committed but due to other complexities around the case they did not put sanctions on the author. [2] The author blamed his own study design for differences in 1 vs 2 formulas when he was challenged about his findings. All 3 of had basically the same constituents. I could go on and on. These reasons are why I approve of the exclusion of those articles because the data is clearly unreliable if not non-existent. Scientific misconduct should be taken seriously because it could have serious health consequences for the public, in this case young infants and children. [3] In fact some people have suggested that it should be crimininalised. [4] By the ‘ghost’ that still haunts hydrolysed formula research, I was referring to the shadow cast by those publications and not the author himself because he is still alive.
You are right, in the majority of cases, the word ‘cautious’ would be appropriate but if a scientist cannot provide datasets when challenged, co-authors allege the research was never performed, let alone the volume of work in the timeframe stated is unreasonable for a single author to have performed, his university suggests scientific fraud and mothers allege their infants were never followed up as stated by the author, I think the safest thing in the public and scientific interest is to disregard his publications in a systematic review. Because misconduct has been detected in other publications unrelated to hydrolysed formulas, [5] even the phrase ‘treat with caution’ is pushing it a bit too far in this case and could mean infant morbidity as a result.
There have been other studies, albeit maybe designed differently and on different products that are available for reviewers to look. Scientists who feel in clinical equipose about hydrolysed formulas' ability to prevent allergies can design newer more robust studies rather than spending millions of pounds trying to perform another study to compare 3 formulas with basically the same product. As of manufacturers, they can easily fund new research, which they might, given the potential financial implications of the finding that there is no consistent evidence that ‘hypoallergenic’ formulas prevent allergies. The problem in this case is that they probably realise the dodginess of the research that they relied upon to boost the market in the first place and the lack of subsequent concrete evidence to support it. If they do, that research clearly needs to be run by independent public research bodies. As for the journals, I think those that have acted should take pride in that they detected irregularities which are now in the public domain and therefore salvaged their reputation which is to maintain scientific integrity and protected the public. I do not think journals should focus on the seemingly 'damaged reputations' when they discover that fraudulent scientists have gone undetected by their existing fraud detection measures. In fact, these are learning opportunities, times for reflection on how best to avoid similar situations in the future to protect scientific integrity.
References
[1] Re: Do hydrolysed infant formulas reduce the risk of allergic disease? A response to Dr Clever Banda. BMJ. URL: http://www.bmj.com/content/352/bmj.i1143/rr-2
[2] Retraction: Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants BMJ 2015; 351:h5682
[3] Sterken E. The impact of scientific misconduct on child health. Public Health Nutr. 2006 Apr; 9 (2):273.
[4] Bhutta ZA, Crane J. Should research fraud be a crime? BMJ 2014; 349:g4532
[5]Payne, D. Nutrition retracts 2001 paper. The Scientist. 2005 Mar 3. Link: www.the-scientist.com/news/20050303/02 (Retrieved 11 March 2016)
Competing interests: No competing interests
Re: Do hydrolysed infant formulas reduce the risk of allergic disease? A response to Dr Clever Banda
Dear Dr Banda
I see that you approve of the exclusion from consideration, the articles published in reputable journals, EVEN IF NOT RETRACTED, where " the ghost of one of the authors " still,stalks us.
That we should be very cautious is only sensible.
It is strange that no one to my knowledge has announced an intention to repeat the studies.
Why not?
Is it not in tne interest of a) infants b) the journals whose name is now somewhat muddied c) the manufacturers who could try to salvage some of their reputation
for the studies to be repeated?
Competing interests: No competing interests
The peak professional body of clinical Australasian immunologists and allergists, the Australasian Society of Clinical Immunology and Allergy (ASCIA) has just published updated 2016 guidelines on the prevention of allergies in infants. [1] They have acknowledged the findings of the recent systematic review and meta-analysis published by Boyle et al. [2] published in the BMJ that there is no consistent convincing evidence to support a protective role for partially hydrolysed formulas or extensively hydrolysed formulas for the prevention of eczema, food allergy, asthma or allergic rhinitis in infants or children. The guidelines now state that “If an infant is not breastfed or is partially breastfed, commercial infant formula should be used until 12 months of age”. The previous 2010 ASCIA guidelines [3] quoted by Boyle et al. recommended partially hydrolysed formulas often with the ‘HA’ or ‘hypoallergenic’ label to be used for the prevention of allergy in children with a strong family history of allergies. This is a welcome development and I would like to congratulate Boyle et al. for carrying out and publishing their review which has had an immediate impact on national guidelines here in Australia. I hope more overseas learned immunology and allergy societies will follow the Australian example soon.
The new change is important as it will potentially reduce costs for families who have been buying the generally more expensive ‘HA’ or ‘hypoallergenic’ brands and again puts breastfeeding rightly back in the limelight. It is important that paediatricians update families on this current available evidence so they can make informed choices for their infants. The big question that will linger on is whether food regulatory agencies such as the Food and Drug Administration (FDA) in the USA or the Food Standards Australia New Zealand (FSANZ) here will take this evidence on board and put new guidance on 'hypoallergenic' labelling of formula milk.
References
[1] Guidelines for allergy prevention in infants. Link: http://www.allergy.org.au/images/pcc/ASCIA_PCC_Guidelines_Allergy_Preven...
[2] Boyle RJ, Ierodiakonou D, Khan T, et al. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. BMJ 2016;351:i974.
[3] ASCIA. Infant Feeding Advice. Secondary Infant Feeding Advice 2008.http://www.allergy.org.au/images/stories/hp/info/ASCIA_Infant_Feeding_Ad...
Competing interests: No competing interests
Prolific and protean, but idiopathic, autoimmune diseases are pandemic and increasing exponentially. Curiously, the exponential increase of autoimmune diseases parallels the exponential increase of vaccines. Since autoimmune diseases and vaccines both relate directly to immunity, it’s reasonable to wonder if vaccines play a causative role in the prevalence and severity of autoimmune diseases. Is autoimmune disease pharmacogenic and iatrogenic? Is autoimmune disease a synonym (euphemism) for vaccinosis?*
*Autoimmune disease, in which our immune system rejects our own body, affects every cell, tissue, organ, and system in our body. Here's a partial list of autoimmune diseases: allergy, anemia, arthritis, asthma, cancer, carditis, celiac, colitis, diabetes, encephalitis, fibromyalgia, hepatitis, ileitis, iritis, nephritis, pancreatitis, thyroiditis, and vasculitis.
Competing interests: No competing interests
Boyle et al. [1] recently published a potentially clinical practice changing systematic review and meta-analysis that showed that there is inconsistent and insufficient evidence to support the use of partially hydrolysed formulas for the prevention of allergies in children as advocated by Western and Australasian immunology learned societies. The authors recommended transparency and prevention of commercial interests from influencing research in this area.
There is literature to show that industrial funding of nutrition-related scientific articles is prone to publication bias with conclusions that favour positive results for the sponsors' products and potentially endangering the public. [2, 3]
In my opinion the only way to sufficiently protect the public from unethical research and publication bias is for the formula industry to sponsor all formula research through national public transparent bodies such as the National Health and Medical Research Council (NHMRC) here in Australia or the Medical Research Council (MRC) in the United Kingdom rather than sponsoring the scientists directly. This is not to say that there aren’t transparent industries out there which could run research studies by themselves ethically, but every measure needs to be taken to protect researchers from finding themselves in a situation of conflict of interest and at risk of unethical practices. The controversial issue of industrial sponsorship and pressure on researchers as clearly exemplified by the suspected fraudulent publications by Dr Chandra whose ‘ghost’ still haunts research on this very topic on hydrolysed formulas. I would like to congratulate Boyle et al. for excluding all of Dr Chandra’s research articles [4, 5, 6] to ensure a valid systematic review and meta-analysis irrespective of whether these have been retracted or not by major journals.
In supermarkets, shelf after shelf is filled with formulas of various brands with a myriad of varying constituents which is a testimony to the extent of commercial competition in the formula industry. With such a competitive environment, wrestling control of the research process from the industrial funders is essential to avoid publication bias. Research in hydrolysed formulas for the prevention of allergies has clearly been ‘contaminated’ by bias as pointed out by Boyle et al. and maybe sadly influenced clinical practice. While medical journals insist on declaration of conflicts of interest, this is clearly not full proof against data fabrication or publication bias of positive results.
There is clearly a need for learned immunology societies worldwide to review their recommendations in this area in light of this review. Whether or not the formula industry can ever be universally capable of truly transparent research will remain a debatable issue.
References
[1] Boyle RJ, Ierodiakonou D, Khan T et al. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis BMJ 2016; 352:i974
[2] Lesser LI, Ebbeling CB, Goozner M, Wypij D, Ludwig DS. Relationship between Funding Source and Conclusion among Nutrition-Related Scientific Articles. Katan M, ed. PLoS Medicine. 2007; 4(1):e5. doi:10.1371/journal.pmed.0040005.
[3] Beasley A, Amir LH. Policy on infant formula industry funding, support or sponsorship of articles submitted for publication. International Breastfeeding Journal. 2007;2:5. doi:10.1186/1746-4358-2-5.
[4] Chandra RK, Hamed A. Cumulative incidence of atopic disorders in high risk infants fed whey hydrolysate, soy, and conventional cow milk formulas. Ann Allergy 1991;67:129-32.1867449.
[5] Chandra RK. Five-year follow-up of high-risk infants with family history of allergy who were exclusively breast-fed or fed partial whey hydrolysate, soy, and conventional cow’s milk formulas. J Pediatr Gastroenterol Nutr 1997;24:380-8. doi:10.1097/00005176-199704000-00005. 9144119.
[6] Chandra RK, Puri S, Hamed A. Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants [correction in BMJ 1989;299:896] [retraction in BMJ 2015;351:h5682]. BMJ 1989;299:228-30. doi:10.1136/bmj.299.6693.228. 2504375.
Competing interests: No competing interests
Re: Do hydrolysed infant formulas reduce the risk of allergic disease
I am grateful to Dr Clever Banda for replying to my questions.
1. May I first apologise for my ambiguous wording in respect of the main author. I was not aware that he is still in the Land of the Living. The word " ghost" used by Dr Banda led me astray.
2. Of course I agree that dishonesty in research is sinful. If dishonesty is proved, those who funded the research AND those who published it, would be expected to seek damages from whosoever was dishonest.
Q. Have the authors been asked for such damages?
3. I agree that it is terrible for incorrect advice to be given to infants. (It is equally bad if grownups are badly advised.)
4. The trial protocols for the research now labelled as suspect must be in the public domain. Unless someone somwehere uses the same protocols and comes to different conclusions, it is unreasonable to ignore the findings published in a REPUTABLE JOURNAL all those years ago.,
Competing interests: No competing interests