Monday, April 30, 2007

Paediatric Grand Rounds Wants Your Post, Please

Mock-up cover for Standing Baby magazineYes, it is out with the begging bowl, as I shamelessly rattle the post collection bag and ask you for your contributions to Paediatric Grand Rounds. As you can see from the magazine cover, we are open to conventional and more off-beat topics.

The next edition of the PGR will be hosted by Moreena at The Wait and the Wonder. Moreena asks that you send submissions to
moreenaATgmailDOTcom
by May 5th.

Clark Bartram is looking for hosts for future PGRs. You can consult both the hosting schedule and earlier editions in the Paediatric Grand Rounds archive.

For more information about the image used in the illustration (from Tedsblog), click on it or visit the detail on Flickr.

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Friday, April 27, 2007

GP Referrals: You Shouldn't Need a Secret Decoder Ring

Decoder mosaic
I was chatting to a parent this morning so I will warn you up-front that some of these disguised, transposed and fictionalised details may not make up a coherent piece but the essence of the story remains.

At the heart of the story is a very young child with respiratory problems. The child is still pre-school but apart from the recurrent illnesses, sleepless nights etc., the parents are (naturally) worried about possible future progression of the problems and their impact on school work, social life, general wellbeing and the myriad things that occupy parents's thoughts.

The child has had many courses of antibiotics but the parents are concerned that there is no improvement. They enquired about a referral to a paediatric respiratory consultant and were dismayed by the 'real life' lead times involved: they asked their GP for a private referral.

The GP in question obliged and presented the parents with a list of names; when pressed to pick one, the GP demurred on the grounds of neutrality and apparently refused to say why he had listed the consultants that he had. The parents picked the most geographically convenient consultant with the shortest waiting-list.

The consultant involved has an excellent reputation. He presented 3 options to the parents:
  • wait and see
  • immediate surgery
  • a protracted course of low-dose antibiotics.
None of these options appeal to the parents. They consulted their GP who declined to comment. At their wits end, the parents will take the child for a second opinion, even if it means waiting for some time.

Interestingly, the GP's list includes a couple of clinical allergists with a particular expertise in respiratory matters. The child has not been assessed for allergy on the NHS. The child has some patterns of illness and symptoms that raise questions as to whether the respiratory problems are indicative of underlying allergies. It is plausible that the GP suspects that the child needs an investigation of the allergic status but has felt unable to declare this for a number of reasons. I have met GPs who are reluctant to raise the prospect of allergy because they know that they have no reasonable expectation of making a referral to an appropriate expert on the NHS.

The parents have opted for a second opinion. They shall consult one of the clinical allergists: they will review their child's options after that time as they will have spent some months 'waiting and seeing'.

Dr. Crippen is familiar with the difficulties that patients have in choosing which consultant is appropriate. He is prepared to help his patients make appropriate choices because he has access to information that patients do not and because:
Dr Crippen is a discriminating and educated consumer of specialist medical care.
There really are times when patients need guidance. I feel that the GP may have been giving some implict advice when he compiled a list that contained some allergists. However, the parents did not know this. They did their research based on what they did know and will now have the inconvenience and expense of consulting a second opinion.

I have no way of knowing what the outcome will be and if the second opinion will endorse the first. It may well be the consultant decides that no further investigation is necessary. People consult their GP for medical treatment or guidance. This is a Good Thing. The GP in this case needed to provide direction and guidance to the parents. If the GP was giving a subtle indication that the child's respiratory problems should be assessed for an underlying allergic mechanism, then he forgot to give the parents the secret decoder ring.

Click on the image for further information on Flickr or look at the following. 1. decoder tshirts, 2. Early Enigma Decoder Machine, 3. decoder, 4. DE CODER

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Thursday, April 26, 2007

Holford Recommends a Nutritional Approach to Hayfever: What's the Quality of the Evidence?

A young boy and his dog in a position of prayer
And please let Shinga read some decent research papers before she explodes.

Several valued correspondents have brought Patrick Holford's nutritional recommendations for people with hayfever to my attention. Holford's PR people are to be congratulated because the same press release appears in many places in the form of articles about dealing with hayfever: one of the most recent of these is in the Manchester Evening News, Supplements to Solve Hayfever Sniffles. There is a more detailed account of Holford's claims regarding particular supplements and hayfever on his own site.

I'm going to state right here that there is negligible evidence to support Holford's claim that among these supplements:
MSM has so many benefits for allergy sufferers that it’s hard to know where to start.
I will enlarge upon why I reject this claim, but for now, I would like to digress onto a pet peeve. It is a recurrent irritation that articles such as the above tend to contain several questionable statements and claim a degree of scientific support that does not exist. However, disagreeing with them takes considerably more effort and time than saying, "That's not wholly accurate". Jon of Holford Watch decided to look into Holford's recommendations about obtaining your Omega 3 from "unfried and unbreaded fish": after a diligent look through the relevant literature, he doesn't find any evidence to support that recommendation. Jon spent several hours on this task.

In my more jaundiced moments, I imagine that it took possibly 4 or 5 minutes for Holford or one of his researchers to find and flick through a paper that seemed to support their point of view. It possibly took another about another 5 minutes to put together the text that extols the virtues of MSM for hayfever/allergies. It took me a couple of hours to identify which study Holford was referring to, to locate it and order it from the British Library, and ditto for the follow-up comments and related literature. I spent more time reading the literature so that I could be confident when I write, "There is a dearth of quality scientific evidence to support the claim that MSM has "many benefits for allergy sufferers": such claims rely on anecdote at best".

Holford appears to be excited about MSM as a supplement to reduce allergic symptoms:
MSM has so many benefits for allergy sufferers that it’s hard to know where to start. In one study, 55 volunteers diagnosed with seasonal allergies were given 1,300mg of MSM twice daily for 30 days. A significant reduction in symptoms of both the upper respiratory tract (including nasal congestion) and lower respiratory tract (including cough) was seen. As long as you’re still suffering from any allergic symptoms, or are in pain, it’s well worth supplementing MSM on a daily basis. While therapeutic intakes go up to 6,000mg a day, I recommend you start with 1,000mg, or half this if in combination with the other anti-allergy nutrients.
The study in question is A multicentered, open-label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis. It is a little surprising that a study with 55 volunteers, 50 of whom actually completed it, was multi-centered. However, the authors readily acknowledged that their study was open-label which is helpful because it allows the reader to form an impression of the probable clinical value of the study before proceeding to read the abstract and contents.
50 subjects completed the study. Those subjects completing the study consumed 2,600 mg of MSM orally per day for 30 days. Clinical respiratory symptoms and energy levels were evaluated by a Seasonal Allergy Symptom Questionnaire (SASQ) at baseline and on days 7, 14, 21, and 30. Immune and inflammatory reactions were measured by plasma immunoglobulin E (IgE) and C-reactive protein at baseline and on day 30. An additional inflammatory biomarker, plasma histamine, was measured in a subset of subjects (n = 5).
The authors of the paper acknowledge that their results demonstrated no improvement in the objective measurements of biomarkers: "No significant changes were observed in plasma IgE or histamine levels". Despite Holford's enthusiasm for the "significant reduction in symptoms" this paper can really not be interpreted that way because there are considerable confounding factors involved in the interpretation of the results.

A follow-up letter to the paper flagged some of the obvious problems about the reporting of the results: Methylsulfonylmethane as a treatment for seasonal allergic rhinitis: more data needed on pollen counts and questionnaire.

Among the many reasons that this paper does not meet standard criteria for a high quality of scientific or clinical evidence is:
  • seasonal allergic rhinitis fluctuates with the pollen count; on low pollen days and towards the end of the season, symptoms tend to improve
  • the authors monitored the daily pollen counts throughout the study but did not include that data in their analysis
  • participants subjectively rated allergy symptoms on a weekly questionnaire, retrospectively recalling the changes
  • the symptom questionnaire is not clinically validated in the way that (say) the asthma quality of life questionnaires are
  • it was an open-label study which means that there was no placebo intervention group but there was also no control group against whom to compare variations in symptoms scores
It should also be mentioned that the study was funded by a company that sells MSM. Of course, sensibly enough, Holford does happen to have formulated a anti-allergy supplement that contains all of the supplements that he recommends (including MSM), and in the quantities that he recommends.

As for some of the remainder of Holford's advice, I have expressed myself at some length on the inappropriateness of IgG testing in the diagnosis of food intolerance. I am not aware of any high quality research that supports Holford's notion that meat and dairy are "mucus-forming [and] pro-inflammatory": however, Jon has some useful observations on this topic. Holford has recommendations about the fruit and vegetable intake:
Choose local, organic produce. Local because there will be less depletion of antioxidant nutrients and organic to avoid pesticide residue which itself is an allergen. Eat plenty of these foods raw.
I'm not a nutritionist, but if "local" is a proxy for recently harvested and less likely to have lost nutrients then it might be helpful to advise people to look at frozen fruit and vegetables. I'm not convinced that there is scientific evidence that would support the claim that pesticide residue is, of necessity, an allergen. Again, if pesticide residue is a concern, it might be helpful to say that some superficial pesticides and fungicides may be removed by washing or peeling. As for raw foods-cooking improves the bioavailability of vitamins in some vegetables. Cooking can make it practical for people with poor teeth to eat some otherwise difficult fruit and vegetables. Lastly, and with some sense of awkwardness, given Holford's frequent emphasis on testing for food allergies and intolerances, I feel that I should mention that some people with oral allergy syndrome are able to eat the cooked version of fruits and vegetables that they are unable to eat when raw.

It was more work than I wanted to dedicate to the topic to discuss why I do not believe that there is evidence of sufficient quality to recommend MSM supplementation to people with allergies. I leave it as an exercise to the reader to consider/discover whether the evidence for the other suggested supplements is any better or the claims any more reliable. But then again, doesn't the journalist who reproduces this material have any responsibility for uncritically regurgitating these claims? Is the misreporting of science and medicine part of the reason why the public is losing faith in the credibility of research?

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Wednesday, April 25, 2007

What Does Allergy UK's Consumer Award for Products Mean?

Art illusions, anaphora etc.
When Muriel Simmons joined Allergy UK she reorganised its finances and introduced a successful endorsement scheme.
The charity realised that an endorsement scheme would benefit three different groups. Firstly, it would provide a vital service to the public; secondly, it would revitalise their own turnover; and thirdly, with one in three members of the population suffering an allergy, an endorsement would supply an obvious marketing tool for manufacturers.

"I felt it would be a service to the public with allergies to say that we had tested the product and found that the criteria laid down by the experts (which were incredibly high) had been met." - Muriel Simmons

The idea evolved from the fact that sufferers were frequently contacting Allergy UK for advice on consumer decisions. They wanted to know which vacuum cleaners, cleaning products etc were most suitable, and Allergy UK realised they could turn this to their advantage...

Some companies had approached Allergy UK about endorsements in the past, without seeing why they should have to pay. But the charity could not risk endorsing a product without scientific evidence, and they could not ask specialists to give their time free of charge to review commercial products. The process had to be treated in a commercial way.
It is difficult for consumers to research appropriate accreditations etc. for testing services or the technical specification and efficacy of various products, so this is a useful service. Manufacturers who have purchased endorsements use them to support their marketing activities. Consumers are confident in their purchases because the products are endorsed by an appropriate body of experts.

YorkTest is endorsed by a number of YorkTest-styled experts; it also holds an Allergy UK Consumer Award that is frequently mentioned in publicity about the foodSCAN tests and MAST panel (multi allergen screening test). Understandably, the nature of the endorsement tends to be blurred when journalists or others discuss the tests and it tends to be shorthanded as a recommendation:
Only antibody tests that use blood like the YORK(tm) test are recommended by Allergy UK.
The Allergy UK (AUK) Seal of Approval has particular criteria; it is awarded to products that:
specifically restrict or remove high levels of named allergens from the environment of allergy sufferers and can be scientifically tested with measurable results.
Those criteria are established in a known research laboratory or are validated from published studies. What criteria need to be met for the Consumer Award?
The Consumer Award is intended for products that will generally benefit allergy sufferers and improve their state of health and wellbeing. The award is given entirely on the basis of consumer opinion, and evidence of this must be supplied from a minimum of 25 consumers. Their opinions can cover anything from durability and ease of use right through to value for money and perceived benefit. This evidence and a product sample will also be carefully assessed by a panel of experts from Allergy UK to verify the consumer's opinions. [Emphasis added.]
Elsewhere, I've seen explanations that the Consumer Award is what manufacturers purchase when they can't afford the testing for the Seal of Approval or they are too small to be able to afford clinical trials. The Consumer Award is for:
products that are of benefit to the public but which do not actually reduce or remove allergens in the environment and cannot be tested scientifically. Alternatively, the company concerned may not be able to afford clinical trials. In these cases Allergy UK can confer the Consumer Award which relies on anecdotal rather than clinical evidence.
I find this a little surprising given the frequency with which remarks that claim clinical validation are attributed to people associated with Allergy UK. E.g., in a Daily Mail item about allergy and intolerance tests, when discussing the foodSCAN intolerance tests:
Maureen Jenkins from Allergy UK says: 'This is a clinically proven test which means it has gone through scientific trials to show that it achieves the same result everytime and can be useful in diagnosing certain food intolerances'.
However, that story is from 2002, before even the publication of the much-cited GUT paper from 2004. If the reference is to unpublished scientific trials that had not been submitted to peer review, then this should have been made clear in the article. I am not aware of any published trial that shows that the foodSCAN tests achieve "the same result everytime and can be useful in diagnosing cetain food intolerances": and, as the reference is to "trials" I would have to have missed several or at least two.

I have examined the published literature, and I think that it is premature (at best) and possibily misleading to advocate IgG testing for the diagnosis of food intolerances. I don't believe that IgG for food intolerances has been clinically proven and I don't believe that there is sufficient basic science research to support the theory as yet. Ironically, I would agree that it would be currently inappropriate to seek a Seal of Approval for the foodSCAN tests or MAST panel even if they were eligible. But, I do think that it would be helpful if the claim that these tests are "clinically proven" were to be dropped. It would be helpful if there were a greater awareness that the Allergy UK Consumer Award is indicative only of anecdotal evidence, supplied by 25 consumers and verified by unindentified members of the original panel who made the award and those who have subsequently endorsed its renewal.

Judging by the audits of YorkTest's customer satisfaction questionnaires, I have no doubt that AUK and YorkTest could provide thousands of glowing customer testimonials. Similarly, having looked into the matter, it is clear that the Consumer Award is not subject to the "incredibly high" testing criteria by experts to which Muriel Simmons referred in the NVCO piece to which I referred at the top.

However, it would be helpful to know what others thought the phrase, "as recommended by Allergy UK" implied about the tests or what they understood by "clinically proven". Did you think that such an award could be made on the basis of anecdotal evidence from a small number of consumers? Did you assume that the endorsement was (at least partly) based on a review of the clinical evidence by clinical allergists and immunologists or active researchers? Would it be useful to know who had endorsed the award and its renewal?

Related posts:

Why Results from an Allergy or Intolerance Test May Be Misleading: Part 1 and Part 2
Self-Testing for Allergy and Intolerance in the UK: Part 1
Truthiness and referenciness make the case for IgG food intolerance tests
More allergy and intolerance testing nonsense: part 1
More allergy and intolerance testing nonsense: part 2
Quote Mining and Misrepresentation: Poor Ways to Claim Clinical Validation or Sound Science
What is the Significance of IgG Antibodies and Testing?
Why IgG Testing for Food Intolerance Is Not As Simple As ABC or Doh Ray Mi

Click on the image or visit Flickr for further information about the images. 1. IMG_2441, 2. IMG_2446

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Tuesday, April 24, 2007

Paediatric Grand Rounds, Year in Review Is Up!

Elmo celebrates a birthday

A year ago, the noted sceptic and neonatologist Dr. Clark Bartram posted the first Paediatric Grand Rounds (PGR). Since then, PGR has grown steadily and is promising to be a lively and thriving creature. As befits the founder of PGR, Dr. Bartram took on the responsibility of reviewing all of the previous editions and putting together his personal selection of the best in PGR: A Year in Review.

It is an interesting compilation. It is difficult to know where to stop but I would, however, have included Dr. Flea's series of posts on childhood vaccinations as one of the highlights of the paediatric blogosphere last year.Of course, that's why it is so interesting to have different editors! So, step up and volunteer your services as host.

Next up to host is Moreena at The Wait and The Wonder on May 6th.

Dr. Clark Bartram is looking for hosts for future PGRs. You can consult both the hosting schedule and earlier editions in the Paediatric Grand Rounds archive.

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When Is the Bullying of Children with Allergies Legitimate? When It's A Defence of Civil Liberties?

Allergies
Slideshow of peanuts and allergy medication.

When I was little my brother used to rub soap over my pillow so that I would wake up the next morning with a severely swollen face, deep-red colouring and blisters. He would occasionally do the same to my clothing and bedding. I would probably have retaliated if it had been any easier to find blackcurrants and disguise them in other foods. You expect this sort of behaviour from young children. I have been very disappointed to learn that similar behaviours persist in some adults. It seems that direct bullying is not sufficient of a burden for some school-children with allergies, they now have to cope with indirect bullying from the parents of children who don't have allergies. It is particularly nauseating that some of these parents seek to cloak their bullying and viciousness in a defence of civil liberties.

The New York Times carries an article by Judith Warner on this topic (it's a subscription piece so there is no direct link): Domestic Disturbance. Allergic Girl of Please Don't Pass the Nuts carries both the full text of the article and a useful discussion in Mean Grown-Ups.
There's an absolutely horrifying article in the current issue of Child Magazine about the food fight now raging between parents of children with life-threatening food allergies and parents of the allergy-free. The latter, apparently, have started to push back against "peanut-free" school regulations to assert their children's natural right to eat whatever they darn well please.

The stories are downright chilling: One parent joked on a message board about having his daughter dress as "the Death Peanut" on Halloween. A North Carolina father at a parent-teacher organization meeting said he'd continue to send his child to school with peanut butter sandwiches and "tell his child to 'smear' the peanut butter along the hallway walls." Another father sent his child to school with a "disguised" sandwich that had peanut butter hidden in the middle of the bread.

There are many ways to read this behavior. On the one hand, it reflects widespread ignorance about the scope and severity of some food allergies, and it also reveals plain old laziness. Some parents and educators sense that peanut worries have come to verge on paranoia. And then there's a sense that some parents are going nuts about food generally.

I sympathize with that feeling – up to a point. There was a time a few years ago when I, too, conflated the anxiety of the merely food-averse with the fears of those whose kids were threatened by potentially fatal allergies. A teacher once told me about a preschool mom who took to following her daughter room to room, and screamed at staff members if they didn't walk the halls with EpiPens strapped to their bodies. The teacher felt that this mother was ridiculous, and I did, too. It's easy to turn a quasi-mocking eye on someone who behaves in this way.

That is, it was easy for me until another mother described to me the experience of watching her son nearly die in her arms after an accidental peanut ingestion. Getting into her skin – feeling the fear and vulnerability that drove her to, she admitted, sometimes maddening behavior – changed everything for me. I'd like it if all parents could at some point force themselves to do this kind of mental exercise. Empathy can be painful – but a little goes a long way.

And empathy appears to me now, in much of what I read, to be in particularly short supply, not only among different groups of parents (all those "wars," Mommy and otherwise) but in the increasingly punitive attitudes of school systems and legislators toward parents and, by extension, their kids. Frequently, I find, there seems to be a kind of studied harshness in the air, an in-your-face obtuseness that tries to pass itself off as some sort of virtue or push for justice...

In every case where there are breakdowns of empathy, children are the ones who really suffer. Whether it's the peanut-allergic kids Child Magazine found ostracized in classrooms and cafeterias, or those whose newly-revealed B.M.I. scores crash-landed them into the world of the "fat," or those whose parents are additionally alienated from school districts that consider them near-criminals – it's the kids who fall victim in the crossfire of adult self-righteousness and officiousness.
Allergic Girl also links to an interesting discussion by Mrs Zum: It's A Sad, Sad World. Mrs Zum discusses a news item about a local debate that has made it into the Connecticut press:
A Connecticut 6-year-old's extreme allergy is pitting concerns about the boy's safety against the right of his schoolmates to enjoy an American classic - a peanut butter sandwich.
Mrs Zum has reproduced some of the breathtaking comments that were posted to the paper. The rebarbative attitude in this comment is typical:
Perhaps if the child is so medically fragile that he cannot be present in a school where peanuts are, he ought to be educated in a different setting - perhaps homeschooled or in a private school.It's a shame he has an allergy, but why make everyone else suffer?
Children suffer because they can't eat a peanut butter sandwich between the hours of 9-3? I've run workshops in pre-schools where more than half of the pupils have a declared food allergy. I don't think that it is possible for schools to ban all substances for which their pupils declare an allergy or even anaphlyaxis. However, I do think that children can readily live without being bullied by proxy by the parents of other children. I agree with one of the blog commenters who writes:
my viewpoint is slightly different than the norm I suppose. I haven't asked my son's school to ban any foods. You see he is ana [anaphylactic] to dairy. Can you imagine if I asked the school to ban all dairy products? So if a school has a "no peanut policy" in place due to allergies and then my son comes along with a dairy allergy (which is just as serious for my son) and they then have to ban that too. What about the next child who is ana to egg, then that has to go too. You can see that it has the potential to become very complicated.
It is unquestionable that when children have allergies, it is psychologically gruelling. In the US, several hospitals are devising support programmes for affected families.
In a study of 17 families with children with anaphylaxis, the authors describe the profound psychosocial impact on parents of knowing an illness can cause death. "I was completely shocked and surprisingly emotional," says Stefanie Jones, who burst into tears when daughter Darby was diagnosed four months ago with egg, milk, wheat, and peanut allergies. "I realized I'm going to have that weird kid at the party with the dairy-free, prune juice cookies."

Children, of course, bear the brunt. "The emotional toll is huge," says Muñoz-Furlong. "It tends to wear them down, particularly after they have a reaction." Some children lose the ability to trust people. They may want to stay home all the time within a controlled environment. If they have a reaction at home, they may become afraid that even their parents can't control the allergy. Others are fearful of food or develop eating disorders. They might become hypochondriac, phobic, or suffer from panic attacks or post-traumatic stress disorder symptoms.
Parents can be exhausted by the effort involved in proving a milk/peanut-free playdate for their children. Paradoxically, because so many parents claim 'fashionable' allergies for their children, it may undermine a full understanding of how deadly serious allergies are for other children.

I don't know what a satisfactory solution to the issue of allergens in the school and wider environment is. I do know that asserting your own right to send peanut butter sandwiches into school and bullying children under the cloak of civil liberties is not even a vague contribution to the solution.

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Saturday, April 21, 2007

Why Results from an Allergy or Intolerance Test May Be Misleading: Part 2

Bronze sculpture of a figure with a migraine by Jose SacalYou might expect a clinical test to have results that would be the same in any laboratory where a sample was tested and to be reproducible, e.g., the same result when tested on a different day. Beyond this, according to Dr. Adrian Morris:
An Allergy Test should reliably identify one or more agents to which the patient reacts on each exposure. These allergens must be the cause of the patient’s immune-mediated allergic symptoms. This reaction need not necessarily be IgE mediated, but may involve a T-cell Delayed hypersensitivity reaction or direct Histamine release from Mast Cells and Basophils. The test should be reproducible and identify the implicated allergen on each occasion the test is done. The allergy should be specific to that allergen with minimal false positive test results (when the test is positive in someone with no allergy), or false negative test results (where the test is negative in a person who is known to be allergic to that allergen). Abnormal (Positive) results should always be associated with clinical allergic disease.
However, although some tests have a high degree of specificity and reproducibility, there are still notable caveats, particularly when testing for food allergens (I shall discuss these in a later post). There are also basic issues concerning the appropriate value and interpretation of diagnostic tests. According to the National Allergy Strategy Group's (NASG) report to the House of Lords Science and Technology Subcommittee that is reviewing allergy and allergic disease in the UK:
Most doctors do not know how to interpet these tests; thinking, incorrectly, that a positive equals an allergy diagnosis. Clinical research is necessary to throw light on this eg in nut allergy, a 'grey area' has been identified in the so called 'positive' range, where 50% of patients are allergic but 50% are tolerant (Clark & Ewan 2003). Another development is to identify the level in a test result above which nearly all patients have allergy (Sporik et al 2000; Hill et al 2000).
There is some concern about the misdiagnosis of allergy and inappropriate allergy or intolerance tests that can harm consumers. The NASG reports that:
Unorthodox and unsubstantiated practices including methods of diagnosis abound in the private sector...This is in part driven by absence of NHS allergy services. Many patients get the wrong diagnosis. This sometimes leads to medical harm; or financial problems for the patients; and wastes NHS funding-unproven private treatment is being paid for by some [Primary Care Trusts].

Even the established tests (specific IgE antibody)-without interpretation-can be misleading. Thus sales of these direct to the public eg supermarket, high street or through the media are harmful. Patients are diagnosed allergic when they are not and inappropriate management follows. Furthermore, there is a lack of quality control and tests in these laboratories can be positive when the same test in a [Clinical Pathology Accreditation (UK) Ltd] accredited laboratory is negative.
It might be useful if consumers had ready access to information about whether or not a testing laborary is CPA accredited or similar but it is rather difficult to find this information even on CPA's own website. Under these circumstances, it would have been helpful if the NASG had named the testing laboratories where such failures had occurred and the specific tests that are known to be problematic.

YorkTest is possibly the best known provider of direct-to-consumer allergy and intolerance tests in the UK; these tests have been endorsed by Allergy UK. However, what does YorkTest have to say about the accreditation for its foodSCAN tests? Well, by and large it doesn't. It tells us about its quality system accreditation: the sort of quality systems that are concerned with appropriate documentation of processes and procedures in most industries.
YORKTEST Quality System Accreditation

Certification to ISO9001:2000
Certification to ISO13485:2003
These accreditations are not related to the validation of the scientific testing and I don't understand why they were included in this section. ISO9001:2000 is a quality management standard and ISO13485:2003 is a medical device standard which sounds more relevant but is mostly about quality management and documentation.

However, Yorktest does give more specific information about foodSCAN:
YORKTEST foodSCAN Regulatory Compliance

Compliance with the European Medical Device Directive 93/42/EEC; for the manufacture of the sterile lancets

Compliance with the European In Vitro Diagnostic 98/79/EC; The blood collection device (for home use) and the reporting of results directly to the consumer in combination (but not including) the above Professional laboratory service, are covered by Annex III Section 6 of the IVD Directive. YORKTEST Laboratories fulfils the requirements of Annex III, Section 6 which include the Design Examination by the Notified Body (UL International).
I'm delighted to learn that YorkTest uses sterile lancets that comply with relevant directives but it might be more useful to know about this CPA lab accreditation that NASG considers to be of such great importance. Sadly, even the impressive sounding In Vitro Diagnostic 98/79/EC does not cover this. It seems that Annex III is about a self-certification process that involves some degree of examination by a 3rd party:
EC Declaration of Conformity. A procedure in which the manufacturer declares to conformity of his products with the IVDD. Applicable to all devices except those listed in Annex II or devices for performance evaluation. All "ordinary" IVD products can be CE-marked using this "self-certification" route. Additionally, for devices for self-testing, a Notified Body shall carry out an examination of the design.
According to the Medicines and Healthcare products Regulatory Agency the IVD Directive 98/79/EC: "covers the placing on the market and putting into service of In Vitro Diagnostic Medical Devices".

There are many standardised food extracts and aero-inhalants for IgE testing but not for food-specific IgG. Because of this, I had expected clearer information about laboratory accreditation or accreditation for YorkTest's IgE tests. However, the issue of accreditation is no clearer for the YorkTest multi-allergy screening test (MAST).
MAST Accreditation
The MAST testing service provided by YORKTEST is compliant with the European In Vitro Diagnostic Directive 98/79/EC; The blood collection system, transport of the sample and the reporting of results directly to the consumer in combination with the above Professional laboratory service, are covered by Annex III Section 6 of the IVD Directive. YORKTEST Laboratories fulfils the requirements of Annex III, Section 6 which include the Design Examination by the Notified Body (UL International).

Since November 2002, the Company has (successfully) been a member of the UK NEQAS (United Kingdom National External Quality Assessments Service for Immunology and Immunochemistry) scheme for measurement of food and inhalant specific IgE’s.
It seems as if CPA(UK)Ltd EQA accredits the UK NEQAS member schemes. It would be helpful if any relevant accreditation were to be clearly stated.

YorkTest made a statement to the House of Lords Subcommittee (pdf) and included a description of its accreditations that it presumably felt to be relevant but don't seem to be indicative of scientific validation.
YORKTEST is keen to differentiate itself from the non-scientifically validated service providers. YORKTEST holds three SMART awards from the DTi, both ISO9001:2000 and ISO13485:2003 Quality Management Certificates, and the Food Allergy and Food Intolerance Testing Services they offer are fully compliant with the European In Vitro Diagnostic Directive 98/79/EC Annex III, Section 6 (self-test) which includes the Design Examination by the Notified Body (UL International). YORKTEST also holds the Queen's Award for Enterprise: Innovation. Despite these accreditations YORKTEST often finds itself grouped with the less reputable organisations and still finds resistance from GPs or clinicians whose patients are interested in exploring YORKTEST further.
As listed in this document, none of these particular accreditations is indicative of scientific validation. A SMART award is the research and development grant scheme for small to medium sized businesses that used to be run by the Dept. of Trade and Industry: I've discussed the relevance of the other accreditations above. As detailed, YorkTest's accreditations do not distinguish it from other companies offering a similar direct-to-consumer IgE or IgG blood testing service. E.g., Cambridge Nutritional Sciences (CNS) lists ISO9001 quality systems as part of its "on-going commitment to customer service" and it uses CE marked items such as sterile lancets. It is entirely possible that CNS have the CPA accreditation that was mentioned by NASG but they neglect to state this explicitly.

Imutest offers allergy and intolerance tests direct-to-consumer. Imutest is currently under new management and there is no information about relevant accreditations on the website. This was a little disappointing as I have seen a previous claim about the clinical validation of Imutest's IgE testing that looked very interesting:
Imutest is a clinically proven IgE allergy test, just like those used in hospital laboratories. In a study of 200 patients referred to an NHS allergy clinic for allergy tests, Imutest correctly identified allergies present with an accuracy of 98% in comparison to the gold standard laboratory test method.
I searched Entrez PubMed but could not find a reference to Imutest and I haven't yet received a reply to my enquiry but I understand that there may be some administrative disarray at present.

I am unconvinced that there is scientific or clinical validation for IgG testing in the diagnosis of food intolerance (see related posts). I accept that IgE testing for some allergies is a well accepted and validated technique (albeit the results should be interpreted by an appropriate clinician and alongside a full clinical history) however I think that it would be helpful if the companies that offer this testing would detail their relevant laboratory accreditation or independent clinical validation of individual tests. In the absence of labs that are members of the same accreditation scheme, it is difficult for consumers to have confidence that the tests are reliably measuring what they are said to measure. Further, unless the laboratories are explicit about their measurement methods and how they convert the results into clinical significance, e.g., what distinguishes severe intolerance from a food that should be 'rotated' rather than eliminated, then this undermines standardisation/relevance of the results. The testing laboratories should be prepared to state their CPA (or similar) accreditation even for a well-understood technique such as the array of IgE tests for allergies: without it, consumers can not be confident that they are getting the quality of results that they are paying for.

Related posts:

Why Results from an Allergy or Intolerance Test May Be Misleading: Part 1
Self-Testing for Allergy and Intolerance in the UK: Part 1
Truthiness and referenciness make the case for IgG food intolerance tests
More allergy and intolerance testing nonsense: part 1
More allergy and intolerance testing nonsense: part 2
Quote Mining and Misrepresentation: Poor Ways to Claim Clinical Validation or Sound Science
What is the Significance of IgG Antibodies and Testing?
Why IgG Testing for Food Intolerance Is Not As Simple As ABC or Doh Ray Mi

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Friday, April 20, 2007

Drugs, Demagogues and the Irregular Verb Theory

Question mark and reminders
Val McDermid is associated with one of the pithiest versions of the irregular verb theory:
I am diplomatic
You are tactful
He/she is a liar
Another, more controversial version, is:
I am a patriot
You are a nationalist
He/she is a terrorist
Or, given some of the recent discussions about the funding source of various studies and publications:
I have an impeccable moral compass
You have a conflict of interest
He/she is a pharma/industrial complex shill
Dr. Stossel has written a piece that asserts his confidence in his own moral barometer in the Boston Globe: Drugs and demagogues. It's well worth reading if you enjoy classical references (which I do) but quite maddening if you were hoping for guidance on how impeccable moral barometers can prevent acknowledged problems such as the disproportionately positive results that are reported for industry sponsored trials. For a taste of the Stossel rhetoric:
IN 427 BC, the Athenians recaptured the town of Mytilene from the Spartans. The historian Thucydides described the intense debate that followed over the fate of Mytilene's citizens, who had collaborated with the enemy. Cleon, whom Thucydides characterized as a violent demagogue, argued for killing them all; Diodotus, who did business with the Mytilenians, recommended mercy.

In siding with Diodotus, Thucydides noted how some people invoke financial conflicts of interest to discredit worthy opponents: "If a man gives the best possible advice but under the slightest suspicion of being influenced by his own private profit, we are so embittered by the idea that we do not allow the state to receive the certain benefit of his good advice." In this case, the state did not benefit, and Cleon prevailed.

Recently the Food and Drug Administration furthered this venerable tradition, when it proposed to keep anyone with a financial interest of $50,000 or greater in a field of medical technology from taking part in an FDA advisory panel in that same field. But why?
Now, I have some sympathy with the notion that expertise in an area that attracts commercial support should not disbar experts from participating in expert panels or guiding research in an area. However, Stossel edges into the rebarbative when he claims that:
medical experts who consult for private companies have the most research agency grant funds. They are the most knowledgeable, inventive, and productive scholars -- which is why corporations want to work with them. Meanwhile, some groups selected for their independence can make terrible recommendations. After having to retract its assertion that certain baby car seats were unsafe, Consumer Reports magazine recently changed its policy of consulting only with experts without commercial ties. The second-best experts do not produce the best results.

The FDA's stated goal for its new policy is "reassuring the public that advice is not tainted." In other words, it is a public-relations exercise. Cleon's descendents in the press and in Congress have praised it.
Seriously? The best researchers all consult for private companies and all of the others are second-best? Concerns about the integrity of publications and the recommendations of expert panels that devise treatment guidelines that can affect millions of people and have enormous implications for healthcare budgets are over-blown and this is nothing more than a public-relations matter?

Stossel reassures us that when patients are desperate (e.g., they are in cancer treatment trials) they report that they don't care about possible financial conflicts of interest. He knows that medical advances depend on the outstanding and entrepreneurial. Interestingly, he details other conflicts of interest that may affect researchers but seems absolutely convinced that although money may be a motivating force to drive excellence it can not corrupt those outstanding spirits who also have a fine moral barometer. For those who lack the latter, he seems pretty sure that credibility among one's peers will act to keep dubious activity in check. He refers disparagingly to those who are perceived as a "company shill" but he doesn't detail how to identify them before they do any harm.

We learn of the dangers of envy and spite.
Similar rules at universities prohibit faculty from obtaining research sponsorship from companies in which they have equity ownership. These rules have discouraged venture capitalists from investing in start-up companies based on the technology of academic inventors. Among the founders of the for-profit biotechnology industry in the 1970s and 1980s are scores of prominent researchers, including Nobel Prize winners -- people who may be excluded from FDA reviews under the proposed rules.
Now, possibly I know too many academics and clinicians who don't work in areas where there is much commercial interest, so I am underestimating the problem of finding experts who don't breach the financial interest conditions. Not withstanding that, I accept that there may be a problem in finding sufficient experts. I would have liked Dr. Stossel to propose a workable policy such as full direct and indirect financial disclosure for experts. Possibly, it might have been worth mentioning the idea that all clinical trials should be registered so that it is possible to track negative as well as positive results.

I need more than being told to rely upon the moral barometers of "the most knowledgeable, inventive, and productive scholars" and the credibility mechanisms that have lately been shown to fail.
Conflict-of-interest demagogues have been appealing to envy and impugning others' motives for 2,500 years of recorded history. When Cleon tarred Diodotus as a liar for hire, 1,000 Mytilenians died. The proposed FDA regulations, if enacted, will be far more lethal.
Well, if that isn't a frightening prospect, what else is? Unless it is the possibility that healthcare budgets should be taxed with paying for gold standard treatment of little demonstrable efficacy. Or that we keep seeing discussions of why so much medical research is rot or why the public is losing confidence in the quality of medical/scientific research.

Flickr credits for the images. 1. question, 2. Questions?

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Thursday, April 19, 2007

Irregular Noun Counting and Supportive Publications for Medinose

Medinose gadget: nasal prong red light sources

I'm frequently reminded of the irregular verb theory. Val McDermid has a pithy example:
I am diplomatic
You are tactful
He/she is a liar
I think that irregular noun counting is also becoming more common. For some time, it seems as if single studies are transformed into plurals and a handful of studies is inflated into "a plethora". (YorkTest make this charming transformation:
There is now a plethora of data showing that people who have adapted their diet according to the YORKTEST results report an improvement in their symptoms. Some of these data have been independently reported [refs to 4 studies, one of which is unpublished, another of which is a poster at a conference and one other that is of dubious clinical relevance (like the unpublished, it is an audit of a customer satisfaction questionnaire). The only clinically relevant paper doesn't fully support their stance as the authors carefully limit its applicability to food intolerance and state that it may be irrelevant].)
The transformation of a single paper/trial into the plural happened recently when I saw Dr. Chris Steele on television; he was promoting Medinose Plus for hayfever. The Medinose Plus is recommended for hayfever sufferers. It involves inserting two visible red lightsources on nasal prongs into your nose, for a few minutes at a time, as a form of light therapy (or phototherapy), two or three times a day while exposure to the trigger lasts (e.g., during grass pollen season). If you have guessed that inserting these lightsources into your nose gives the unseasonal yet jolly appearance of Rudolph the Red-nosed Reindeer, then you are correct.

Dr. Steele appeared on This Morning: the Medinose text says:
Using photo therapy (light therapy) medinose promises to practically eliminate allergic symptoms such as congestion, runny nose, watery eyes, and headaches within a couple of weeks of use. Using photo therapy, Medinose inhibits the release of histamine, relieving or even completely eliminating allergic reactions and complaints in a natural way.
Now, on his own website, Dr. Steele says,
These products have been featured on my TV, Radio or Print spots. Please note that I am NOT endorsing them or recommending them, this information is provided for your convenience only. All information has been provided by the manufacturer/retailer.

Where possible I have provided a direct link to allow you to buy the item online.
This is a little disingenuous. On his website, Dr. Steele has this description of the Medinose but he fails to repeat the warning that the information is (presumably) from the manufacturer/retailer (even quotation marks would have helped, as would not repeating the text in the running banner at the top of the page):
Medinose inhibits the release of histamine, relieving or even completely eliminating allergic reactions and complaints in a natural way. The body is not burdened by drugs and Medinose has no side effects...

I recently received this customer testimonial from the manufacturer which shows that the product does work.
No, it doesn't. It shows that the person who provided the testimonial had a positive experience. In the literature that I've seen (of which, more below), there is no indication that there is any evidence that Medinose "completely eliminates allergic reactions and complaints". The literature doesn't detail any direct measurement to prove the inhibited release of histamine. However, on the testimonial webpage, Dr. Steele does mention that he was sent the testimonial by the manufacturer: at the top of the page, in a size 8 font, in light grey on the white background. But still, he did mention it...

In the item that I saw on television, Dr. Steele said that there were papers and trials (plural) to support the use of Medinose. He quoted the results and reported that he had seen the photographs of endoscopies that demonstrated a reduction in rhinitis swelling after use of the Medinose.

I am disappointed that Dr. Steele referred to papers and trials (to emphasise, both in the plural) but I could only find one specific paper: Narrow-band redlight phototherapy in perennial allergic rhinitis and nasal polyposis (presumably the source of the photographs).

Looking at the site of the distributors, most of them refer the reader to newspaper items for information about Medinose and its mechanism of action. I did find a site that also claimed that "[c]linical double blind randomized trials have been undertaken" [my emphasis, to highlight the plural] but, again, they only link to the above paper (singular). What is it with the plurals? Do references to a clinical paper bring out royal grammar in line with the first person plural-does this account for the irregular noun counting?

Entrez PubMed has 17 articles on phototherapy and rhinitis; however, the other papers discuss the use of different light spectra and wavelengths (10 discuss ultraviolet light and one of these includes the red light; most of the remainder do not provide the abstract or sufficient detail).

Note that the title refers to perennial allergic rhinitis and not hayfever (seasonal allergic rhinitis): the difference is that perennial allergic rhinitis typically involves 'indoor' allergens such as house dust mite and pet skin flakes. However, the majority of the current promotion (understandably) emphasises its role in hayfever symptom alleviation.

Oddly enough, Medinose makes an appearance in the Daily Mail's Hayfever Survival Kit. The journalist claims:
with the help of two of the country's leading allergy experts - Jonathan Brostoff, professor of allergy and environmental health at King's College, London, and Dr Alexandra Croom, consultant allergist from Glenfield Hospital, Leicester - we show you the treatments that have been proven to work.

Whether you're a first-time sufferer or a veteran of 20 summers, these are the remedies that will make a difference.
However, it is difficult to know when any of the remedies have been recommended by the experts. In the Pros and Cons footer to the item about Medinose, the Cons acknowledges,
Scientific data behind this sort of product is limited.
I expected rather more of something which claimed to show me "the treatments that have been proven to work" (my emphasis).

Several newspaper articles and the Medinose FAQ of one distributor detail the influence of Medinose on a variety of symptoms:
Swelling of the eyes and other allergic symptoms arise due to the release of the substance histamine from the mast cells in the nasal mucous membranes. Photo therapy with the Medinose works via the nasal mucous membranes. However, by using red light therapy, it isn’t only nose complaints that disappear, but also the oppressive feeling associated with allergies, watering or swollen eyes, coughing, itches and headaches.
The claims extend beyond efficacy for hayfever to other allergies:
The Medinose helps with allergies of the nasal mucous membranes i.e. not just hayfever, but also animal hair and house dust allergies.
The FAQ also says,
The Medinose has undergone extensive clinical testing, with over 70% of patients reporting a significant reduction in allergic symptoms.
According to Healthyliving (Ireland), "Medinose has already been proven and tested in thousands of cases!" I have no opinion as the the efficacy of Medinose; I have never met anyone who used or prescribed it (although several parents have now asked me about it, following all the recent publicity) and there is a distinct lack of clinical literature. The only published paper is from 1997 and I'm still waiting to see a copy from the British Library. However, I do know that the sole paper can not possibly be interpreted as evidence of "extensive clinical testing". This was not a multi-centre research project involving hundreds or even thousands of people with allergic rhinitis. There were "50 patients with allergic rhinitis and 10 with nasal polyposis" in the treatment arm of the study and "[t]wenty-nine rhinitic patients and one patient with polyposis" in the placebo group who used a sham light. The treatment schedule lasted for 14 days.

The researchers evaluated the outcome of the treatment by assessing the participants' symptom scores and a clinical assessment that included pre-treatment and post-treatment videotaped rigid and flexible nasendoscopy.
[I]mprovement of symptoms was reported by 72% of the allergic rhinitis patients and objective improvement was endoscopically demonstrated in 70% of them as compared with 24% and 3%, respectively, in the placebo group. These differences were significant. No improvement was obtained in any of the patients with polyposis.
I need to see the full paper before I can comment on the extent of the changes and the clinical significance associated with them. However, even with the paper, there is no evidence that the beneficial reduction of swelling in the nose continues beyond the 14 treatment days, or even with continuous use. Although a reduction in nasal swelling is a useful proxy, it is not direct evidence of a reduction in histamine production.

The only objective assessment in the paper was the nasal examination. Despite the optimism of the distributors and the newspaper articles, it is not possible to claim that there is any verifiable evidence of efficacy for the "oppressive feeling associated with allergies, watering or swollen eyes, coughing, itches and headaches".

The authors of the paper conclude their abstract as follows:
Allergic rhinitis, if uncomplicated by polyps or chronic sinusitis, can be effectively treated by narrow-band red light illumination of the nasal mucosa at 660 nm, with marked alleviation of clinical symptoms. Whenever possible, candidates for phototherapy should be selected by endoscopic examination. [Emphases added.]
I've read a number of articles about the Medinose and browsed the websites of several distributors. No articles or product descriptions that I've seen have mentioned that the device is not recommended for people with polyps or chronic sinusitis. Nor have any of the journalists or distributors mentioned the recommendation that candidates should be selected on the basis of an endoscopic examination. It is entirely possible that the journalists and website copywriters consider that the cost of the Medinose (around £80) and the 30 days moneyback guarantee mean that it would be cheaper and more convenient for some people to purchase and test the product (and return it if necessary) than attempting to obtain a timely professional opinion, but it would have been useful if they had acknowledged the recommendation of the authors of the clinical study.

Allergy UK offers advice on the self-management of hayfever.

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Monday, April 16, 2007

Reporting Science: Who Is Interested, Who Is Offended?

Black and white image of a revolving door: text on the floor reads, 'I'm afraid of revolving doors'
Blogs that covers scientific or medical matters frequently criticise both the inadequate and uninformed coverage of these issues in mainstream media while despairing at the ready coverage given to (say) anti-scientific or pro-CAM topics. Too often, science or health journalists seem to reproduce a press release about a study uncritically and make no attempt to check the underlying science, hypotheses or results of the studies or trials.

We rely upon journalists of various media to read and understand studies that are of general interest and to report upon them accurately. However, as Goldacre expresses it, although:
newspapers like to fantasise that they are mediators between specialist tricky knowledge and the wider public...I wouldn’t be so flattering. In fact, if you have access to the original journals, you can see just how rubbish things can get.
I have much sympathy with Goldacre's view however I am mindful that the Royal Society does place some of the blame with scientists:
A problem arises though when controversial research designed to provoke a debate within the scientific community is reported as gospel by the general media.

At best, it reduces trust in scientists and the media; at worst, it can lead to people making poor choices and harming their health...
Recently, there have been discussions as to whether scientists fail to understand the necessity of framing their knowledge and arguments so that they can be understood by their audience.
Frames are a model used in communication studies to try and explain how people interpret information, and also to explain why sometimes the information itself seems to be irrelevant to the final opinion people have of an issue.That is because the same facts, when presented from different point of views (because that is really what cultural, political, religious etc influences create - a point of view) generate different reactions from different people. Framing theory explains how how people process information; and a better understanding of that process can help us make communication more efficient.
Nisbet and Mooney have taken the argument further with the April 15 publication of Thanks for the Facts. Now Sell Them. They illustrate the debate about the commincation of science by highlighting the raging controversy around the public discussion of evolution, Intelligent Design and creationism.
We agree with Dawkins on evolution and admire his books, so we don't enjoy singling him out. But he stands as a particularly stark example of scientists' failure to explain hot-button issues, such as global warming and evolution, to a wary public.

Scientists excel at research; creating knowledge is their forte. But presenting this knowledge to the public is something else altogether. It's here that scientists and their allies are stumbling in our information-overloaded society -- even as scientific information itself is being yanked to center stage in high-profile debates.

Scientists have traditionally communicated with the rest of us by inundating the public with facts; but data dumps often don't work. People generally make up their minds by studying more subtle, less rational factors. In 2000 Americans didn't pore over explanations of President Bush's policies; they asked whether he was the kind of guy they wanted to have a beer with.

So in today's America, like it or not, those seeking a broader public acceptance of science must rethink their strategies for conveying knowledge. Especially on divisive issues, scientists should package their research to resonate with specific segments of the public. Data dumping -- about, say, the technical details of embryology -- is dull and off-putting to most people. And the Dawkins-inspired "science vs. religion" way of viewing things alienates those with strong religious convictions. Do scientists really have to portray their knowledge as a threat to the public's beliefs? Can't science and religion just get along?
I don't accept that scientists don't know how to frame complex issues or write for a general audience (both Ben Goldacre of Bad Science and the contributors to Scienceblogs are evidence of this).

There does seem to be a dearth of mainstream media outlets for good science. Health and science journalists argue that editors are unwilling to devote extensive feature space to science and health despite the vast amounts of newsprint that are given over to mis-reporting of these issues. Some journalists argue that they are discouraged from publicising criticism about some self-tests for fear of alienating advertisers (however, as there is comparatively little money in CAM for individual practitioners unless they are media superstars and even well-known purveyors of self-tests such as YorkTest say that they spend little on advertising, this seems rather specious). Writing about dubious allergy tests, Dr. Adrian Morris claims that:
It is the author’s and Warner’s experience that health journalists are unlikely to investigate or expose these pseudo-scientific tests as fallacious for fear of alienating their “complementary medicine” readership [ref]. [The Warner reference is to his editorial on Allergy and the Media.]
Articles that debunk the poor science behind various CAM and self-tests might attract criticism from an audience that is in sympathy with them but I would be surprised if that is sufficient to deter any interested editors or commissioners. However, it seems as if Orac is in agreement with the Morris and Warner viewpoint. He describes:
the script for most TV news stories about "alternative" therapies: lots of testimonials, no studies, and a brief blurb from the token skeptic whose words are overwhelmed by those of the credulous...If you wonder why people believe in woo so much and have so little clue about evidence-based medicine, you have but to look at how these issues are reported in the media to see one major reason why. Between credulous producers who believe despite published medical studies saying otherwise that [insert your favourite woo or CAM and] bubble-headed physicians willing to report whatever such producers think the audience wants to hear, it's a wonder that evidence-based medicine ever gets reported at all.

On occasion, I've been known to daydream about being one of these talking head physicians doing these stories, leaving aside the fact that I'm not telegenic and that I have a face perfect for radio and a voice that's best for blogging...Of course, even if those obstacles were overcome, I wouldn't last past one or two segments about any alternative medicine. Even if I could tone down my skepticism considerably, to the point of nonsarcastic wishy-washy-ness, that wouldn't be enough. If I expressed a skeptical, strictly evidence-based viewpoint, the audience would soon be calling up the station demanding my firing, and I'd be tossed out of there on my behind.
Perhaps unreasonably, I like Goldacre's more optimistic view of the public:
Alongside the best efforts to empower patients, misleading information conveyed with hyperbole is paradoxically disempowering; and it’s fair to say that the media don’t have an absolutely brilliant track record in faithfully reporting medical news...

Only those who have never met the full range of people in their community will ever claim that the public are stupid: in most doctors’ experience, people are almost universally sharp witted. Where they are misled, someone has worked hard at the job.
Unfortunately, once a bad idea has attained universal currency it becomes part of the frame by which we interpret subsequent information. E.g., both Patrick Holford and Gillian McKeith promote the use of self-tests as a means of empowering people. However, it is not empowering to be able to mis-diagnose yourself and follow needless allergen-avoidance techniques. More generally, it seems harmful that people are being encouraged to believe that modern life is harmful rather than safer and healthier than even comparatively recent history.

Although he was writing about research on guns, Dezhbakhsh famously wrote:
The academic survival of a flawed study may not be of much consequence. But, unfortunately, the ill-effects of a bad policy, influenced by flawed research, may hurt generations.
Frequently, I think Dezhbakhsh's insight when I read Junk Food Science (see, e.g., Baby Fat Fears or any of the articles that address the general hysteria about the obesity epidemic). I think about it when I read about parents who are still terrified when they vaccinate their children because of the MMR-autism reporting.
...deciding to go with MMR, and taking my son to be vaccinated was still one of the most terrifying things I have ever done. I think there is little that is more horrifying to a parent than the idea that your own actions could directly and irreperably harm your child. I am a rational individual, and a strong proponent of the scientific method, and all that I had read on this subject could still not completely eradicate that fear.
It seems that mainstream media has a lot of influence in perpetuating flawed science and little interest in disseminating robust criticism of what passes for science even when it has an adverse affect on spending policies or matter of public health and interest.

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Sunday, April 15, 2007

Why Results from an Allergy or Intolerance Test May Be Misleading: Part 1

Bronze sculpture of a figure with a migraine by Jose SacalThere are significant problems involved with direct-to-consumer (DTC) testing for allergies and intolerances. Dr. Scadding characterised some of these self-tests as a waste of money and in response to a question about whether she considered that these tests were sufficiently regulated, she answered, "They should be banned". She went on to outline some of the harm that is experienced by children when they are misdiagnosed or if they pursue unnecessary allergen avoidance.

Dr. Scadding discussed a recent example that illustrates some of the potential problems for consumers who have access to direct-to-consumer tests.
Dr. Scadding: For example, I saw a child this morning before coming here and she had...We did skin tests that are well recognised and she had skin tests to house dust mite and also to tree pollens. Two kinds of tree pollen. She has absolutely no symptoms referable to the tree pollen whatsoever. She does not have Spring Hayfever. She has good symptoms related to the house dust mite, so I treated her with house dust mite avoidance and anti-allergy therapy.

If she had got a kit, then she would have felt that she was tree pollen allergic as
well and something had to happen about that. She has sensitisation but not clinical disease. And if you do a test, only about half the people with that positive test will have clinical disease.

So, you can not have self-testing kits: they're going to lead to mis-diagnosis, mis-allergen avoidance. You need both the test and a detailed history taken by somebody who has some experience of allergy history taking and interpretation of tests
. [Emphasis added.]
There are additional problems with blood tests which argue against their usefulness as a sole diagnostic aid for allergy. It is well-known that some people have cross-reactivity among allergens: e.g., an allergy to birch pollen, resulting in Springtime Hayfever, may co-exist with an oral allergy syndrome response to raw apple.
The same reservations expressed for skin prick testing-namely, poorly standardised food allergen extracts-are also true for the various methods for determining serum concentrations of allergen-specific IgE against food. Another major problem with the newer and technically highly sensitive methods is that they detect the many clinically insignificant serological cross reactions, in which IgE raised against and directed towards epitopes on, for example, grass pollen, also binds to wheat proteins, but without any clinical significance of the finding.
It is a common finding that the results of allergen-specific IgE blood tests should be interpreted with caution, particularly any weakly positive results in individuals with high serum concentrations of total IgE.

Dr. Adrian Morris provides a very helpful overview of some of the pitfalls of various allergy tests. He reports that:
The negative predictive value of food allergy testing is good - if a test is negative, then there is a 90% chance of there being no allergy to that food., but the positive predictive value is less specific - a positive test indicates sensitisation to that food but does not necessarily confirm a clinical allergic response will occur...Some foods such as milk and certain fruits contain a large number of different potential allergens and one has to be aware that a specific RAST may only test a few of the potential allergens in the food. Some people who are perhaps sensitised to a minor allergen in a particular food may RAST test negative, when in fact they are allergic to that food. [Emphasis added.]
Dr. Adrian Morris discusses an unusual presentation of food allergy in which
patients develop itching, urticaria, angioedema and upper airway obstruction with bronchospasm during or shortly after strenuous exercise taking place within a few hours of eating certain foods. This allergic condition may occur up to 12 hours after eating wheat, celery and shellfish especially prawn. These patients have no reaction to the foods if at rest. It is most commonly seen in female athletes usually under the age of 30years. [Emphasis added.]
It is not possible for any of the conventional allergy testing methods to identify exercise-induced food anaphylaxis and it highlights why it is essential that individuals who are investigating possible allergies need the guidance of appropriately qualified and experienced clinicians.

Dr. Morris also discusses foodstuffs that don't contain histamines but that may trigger histamine release in some people that may resemble classic food allergy symptoms although no IgE mechanism is involved.
Foods that have been implicated in this type of reaction include Egg white, shellfish, strawberries, chocolate, citrus fruit, tomatoes, fish and pork meat. The histamine liberated in this reaction will cause symptoms that may mimic true food allergy.
Dr. Morris discusses the natural history of food allergy in children and adults. A higher percentage of children have classic, IgE mediated food allergies but 80% outgrow them, leaving 1-2% of adults with these allergies. However, it is notable that:
If foods are completely avoided, up to 30% of adults will become clinically non-reactive to an offending food over a 2-year elimination period. They will however remain atopic - that is maintain a positive Skin Prick Test or retain specific IgE antibodies to the food, but have no reaction if they eat the food.
So, even for an accepted testing methodology such as IgE, the results of these tests need to be interpreted appropriately by an expert who has taken a good clinical history. An expert can advise individuals as to whether their tests results and and clinical history indicate the need for allergen avoidance which can be gruelling, disruptive and expensive. Expert clinicians can also give appropriate guidance on allergies which can be life-threatening.

Commentators such as Patrick Holford praise the availability of self-testing kits and ascribe dubious motives to others:
some health professionals just haven’t kept up to date. Perhaps it’s because a ‘home test’ takes the power away from the professional and puts it in your hands.
However, it is more plausible that experienced clinicians such as Dr. Scadding have justifiable reservations about the suitability of such tests for the home market.

As I've outlined in other posts, there may be a range of consequences for children who follow a restricted diet, particularly ones that eliminate foods that are a significant supply of calories or nutrients or are so restrictive that they cause significant social difficulties.

Related posts:

Truthiness and referenciness make the case for IgG food intolerance tests
More allergy and intolerance testing nonsense: part 1
More allergy and intolerance testing nonsense: part 2
Quote Mining and Misrepresentation: Poor Ways to Claim Clinical Validation or Sound Science
What is the Significance of IgG Antibodies and Testing?
Why IgG Testing for Food Intolerance Is Not As Simple As ABC or Doh Ray Mi

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Saturday, April 14, 2007

YorkTest and the Number Needed to Treat in Food Intolerance Tests

A young boy and his dog in a position of prayer
And please let Shinga read some decent evidence before she explodes.
Let's face it. The Number Needed to Treat (NNT) is a nuisance. Boring statisticians and people who want a fuller understanding of results from clinical trials bang on about its usefulness but isn't it about time that these people got a life? Because in any clinical trial, we all know that the important people are the ones for whom the protocol worked, particularly if it means that it will at some point provide someone with beans on toast, a roof over the head, a really nice box of pencils or a car...

Who cares about the people who couldn't comply with a protocol because it was too onerous to (say) exclude wheat, milk, egg, corn and soy from the diet? Who cares about the people who don't stick with their anti-hypertension medication because they can't hack the leg cramps, the swelling or the nausea? You can't legislate against lack of self-discipline or, frankly, moral fibre. There, I've said it. By and large, if you don't get anything out of these trials then you weren't really trying. Unless, of course, you were in the placebo group. Whatever. I'm just saying that if people can't be bothered to follow the advice that you give them then they don't deserve a place in your results analysis.

Say that I knew for a fact that when people follow my advice and give up sugar, dietary fat, milk, wheat, soy and keep to a low-sodium regime of around 1g per day (not a real suggestion, just an example), then they keep their blood pressure within bounds. Is it really my fault that for every 100 people who tried to follow this, 98.5 found it impossible over a 3 week test period and that 1.2 gave up after 5 weeks? For the people who complied it was really successful, why should I have to talk about the people who didn't? (If my example seems a little disingenuous, consider this rather charming extract from Dr. Hart's post-meeting statement:
In Febrary a major audit of over 5000 people who had taken a YORKTEST food intolerance test was published in 'Nutrition and Food Science'. The feedback YORKTEST has received demonstrates that many people in the medical profession are not convinced of the role of IgG as an indicator of food intolerances. YORKTEST does not claim to fully understand the mechanisms involved, but the trials, surveys and anecdotal reports consisistently show that 3 out of 4 people, who follow the advice given by the YORKTEST test report, get significant relief from their symptoms. [Emphasis added although I really wanted to highlight the appeal to anecodote.])
Anyway, because epidemiologists and other number-handlers thought that just concentrating on the people for whom something worked could give misleading results, as could concentrating on percentage risk reductions, absolute and relative risks and so forth, they developed the NNT (Slate has a good discussion of this in The crucial health stat you've never heard of). In Slate's example, a trials for a statin reported a 31 percent relative reduction in heart attacks—but only a 2.2 percent absolute reduction (from 7.5 percent to 5.3 percent).
Suppose that 100 people with high cholesterol levels took statins. Of them, 93 wouldn't have had heart attacks anyway. Five people have heart attacks despite taking Pravachol. Only the remaining two out of the original 100 avoided a heart attack by taking the daily pills. In the end, 100 people needed to be treated to avoid two heart attacks during the study period—so, the number of people who must get the treatment for a single person to benefit is 50. This is known as the "number needed to treat."

Developed by epidemiologists in 1988, the NNT was heralded as a new and objective tool to help patients make informed decisions. It avoids the confusing distinction between "relative" and "absolute" reduction of risk. The NNT is intuitive: To a savvy, healthy person with high cholesterol that didn't decrease with diet and exercise, a doctor could say, "A statin might help you, or it might not. Out of every 50 people who take them, one avoids getting a heart attack. On the other hand, that means 49 out of 50 people don't get much benefit."
When Dr. Scadding gave her useful opinion to the House of Lords Subcommittee hearing that IgG tests for food intolerance are a waste of money, she referred to a paper that is much cited by YorkTest and other laboratories that offer IgG measurement for food intolerance tests.
In the Gut paper, which is the best paper produced, the sham group did not avoid dairy or wheat which are the two major problems with IBS patients and therefore it's not surprising that at the end of the survey there was a 10% difference. In that paper you needed, the number needed to treat was 9, whereas if you do an exclusion diet the number needed to treat is somewhere between 1 and 2.5. [Emphasis added.]
Oddly enough, although I found Dr. Scadding's summary of the findings to be admirably clear, Dr. Hart of YorkTest felt the need to clarify the issue in her post meeting statement to the House of Lords committee.
The independent studies which have been carried out include a double-blind placebo-controlled trial in IBS published in GUT which, for clarity in response to other statements made during this inquiry, showed that the number needed to treat for compliant patients was 2.5. [Emphasis added.]
Really? Dr. Hart feels that dragging in a use of the number needed to treat that goes against standard and sensible usage of the statistic in any clinical trial clarifies matters?

I've discussed the Gut paper elsewhere and reported that the authors were punctilious in limiting the scope of the applicability of their findings and speculated that:
[I]t is entirely possible that IgG antibodies may be important in IBS, where we now know that there is an inflammatory component in some cases, whereas they may not be relevant in food intolerance in general. [Emphasis added.]
Dr. Scadding's opinion is in line with that of Dr. Hunter who commented on this paper in The Case for IgG Testing Remains Doubtful.
The percentage of patients showing substantial benefit from this diet is disappointing. In studies using a well conducted and rigorous elimination diet, the "number needed to treat" is between 1.5 and 2.2 [refs]. The "number needed to treat" in this study was 9. (The value of 2.5, calculated on the basis of those who fully complied with the diet, abrogates the intention to treat principle.)
Now, if I were a researcher on these trials, and I'd advised people to eliminate 4 food items from their diets and they failed to follow my advice I might be a little irked. I might be frustrated that they were spoiling my results. Particularly if I knew that when people complied with my advice then the NNT was only 2.5. But, what with one thing and another, I would have to accept that other researchers might think that the fact that so many people couldn't follow my advice was relevant, which is why I would have to include the total number of participants in my analysis of the results and the NNT rather than restricting it to those lovely people who followed my advice.

In the Gut paper, 9 people had to follow the restricted regime of foodstuffs for 1 to show benefit (over the 3 months of the study). Even when the participants did comply with the restricted regime, the NNT was 2.5, so for every 2.5 people who complied, 1 showed benefit. It is socially-restrictive and even psychologically gruelling to follow an elimination diet; it certainly adds to the difficulties of day to day life. This is why it is important to discuss the number of trial participants who were unable to comply with the advice that they were given, even over as comparatively brief a period as 3 months.

Dr. Hart is a biochemist. She must have a full understanding of NNT and why you calculate it from the total number of participants and not just the "compliant patients". So, in what way does her post-meeting statement clarify matters for the committee, particularly as it involves an inappropriate estimate of the NNT? Several of the committee members have no scientific background, it might be a little unkind to expect them to grasp the difference between the agreed use of NNT and a deprecated use of NNT that is calculated only from the "compliant patients".

In her post-meeting evidence Dr. Hart discusses YorkTest's Scientific Advisory Board.
In order to provide scientific support for their services, YORKTEST established a Scientific Advisory Board of independent scientists, leading medical consultants and dieticians to advise the company on clinical trials, exploring the science behind the various tests as well as reviewing and advising on the supporting materials and advisory services offered by YORKTEST to its customers.
Well, it might really help matters if somebody on that Scientific Advisory Board explained the appropriate calculation and meaning of NNT. It would be fascinating to know who is on this board and whether or not it includes any clinical allergists or immunologists.

I still feel like I'm trapped in the scene where Father Ted is trying to explain perspective to Dougal by using toy cows as props and pointing to cows in a far-away field:
Father Ted: Now concentrate this time, Dougal. These
[he points to some plastic cows on the table]
Father Ted: are very small; those
[pointing at some cows out of the window]
Father Ted: are far away...
Sound science...wishful thinking. Verifiable evidence...anecdote. NNT calculated from all of a trial's participants...NNT calculated from "compliant patients".

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