Homeopathy Awareness Week and hay fever

This year Homeopathy Awareness Week (14^th to 24^th June) will focus on hay fever.  The event is being promoted by the British Homeopathic Foundation, a charity closely connected with the Faculty of Homeopathy, the UK’s organisation for medical doctors who also practise homeopathy. 

Their website encourages people to “trust homeopathy”.  So, decided to improve my personal awareness of the evidence that homeopathy will do anything to help this unpleasant seasonal complaint. 

After all, given that this event has the backing of actual doctors – albeit homeopaths – I would expect this campaign to some serious evidence behind it. 

So, setting aside my qualms about the basic plausibility of homeopathy, I searched the PubMed database to see what I could find.  Would the literature on balance back the campaign message that homeopathy can help with hay fever? 

Searching for “allergic rhinitis AND homeopathy” along with “hay fever AND homeopathy” turned up a total of 53 articles. (See References – Search Results). 

How to make sense of this list?  First, not all the papers were relevant to assessing the efficacy of homeopathy as a treatment for hay fever.  For instance, Becker-Witt et al (2004) was, “aimed at characterizing patients seeking homeopathic care and their treatment.” Poitevin (2006) explored a framework for a putative relationship between allergy and homeopathy. 

Similarly, the two trials reported by Witt et al (2005, 2008) were not relevant to the question at hand: they tracked multiple CAM interventions for multiple ailments.  And although homeopathic interventions for rhinitis were included, this is not necessarily the seasonal variant: hay fever. 

Other articles reported surveys:  Damase-Michel et al (2004) sought, “to determine whether community pharmacists recommend appropriate medications and give valid information to pregnant women.” Lynöe et al (1997) surveyed the attitude of 600 medical researchers to, among other things, the homeopathic treatment of hay fever. Whilst Pedersen et al (1996) surveyed Norwegian doctors’ attitude to cooperating with homeopaths. Finally, Félix Berumen et al (2004) assessed the frequency with which different types of alternative medicine were used for the treatment of allergic diseases in patients attending a clinic at Monterrey’s University Hospital. 

Thompson et al (2008) ran a, “pilot data collection study within a programme of quality assurance, improvement and development across all five homeopathic hospitals in the UK National Health Service.” 

Some of the articles did not actually discuss hay fever (Haidvogl, 1990; Hyland and Lewith 2002; Reilly et al 1994).  Whereas Yamagiwa (1997) looked at the application of a measurement technique: acoustic rhinometry (AR). 

No details were available in English for a number of articles (Aly 2000; Crossay, 1975; Falck 1988; Guerrier et al, 1977; Häussler and Wiesenauer, 1982; Samsonova et al, 2006).  

Finally, the article in Health News (2000) does not appear to be a trial.

Assessment method

This done, I was sorely in need of an objective method for separating the wheat from the chaff.  This is important; as Linde et al (1999) point out, in their analysis, “more rigorous trials tended to yield smaller effect.”  Clearly, if the assessment of homeopathy is to be fair, then any assessment must be based on the “more rigorous trials”. 

I decided to follow the general approach of Bausell (2007)^*, informed by other reliable insights.  So I followed his suggestion of not giving credence to anything published in CAM journals. 

Bausell also suggests giving more credence to trials conducted in English and Scandinavian language speaking countries (Vickers et al, 1998).  Interestingly an under-reported aspect of Shang et al (2005) is that the results for homeopathic interventions not published in English are generally more favourable than those which are (p=0.05, a close-call I know).  This confirms that, in this case, it’s generally better to look at the literature available in English. 

Now to some methodological considerations:  a trial that does not randomly assign participants to either treatment or a control group, using an appropriate placebo indistinguishable from the therapy being evaluated, will not provide a reliable answer.  The same goes for a trial where both clinicians and participants are not ‘blinded’ to who is receiving the treatment and who the placebo.  Again Shang et al (2005) demonstrated that the absence of double-blinding (p=0·017) and inadequate or unclear generation of patient allocation to treatment or control groups (p=0·024) tends to (unfairly) favour homeopathy. 

If random assignment to either treatment or control is used, then tests of statistical significance are appropriate.  A trial that does not deliver a statistically significant result will be viewed as negative.  I know that some may demur on this point.  But given that homeopathy is most likely a placebo treatment, it follows that the best experiments are likely to show that they are equivalent.  This would just be confirming the most plausible explanation of homeopathy.  So, calling a non-(statistically) significant result ‘inconclusive’ is merely begging the question.  After all, homeopathy is not likely to actually be worse than a placebo. 

I must admit to being quite taken with a comment by Fisher (1935): 

“Every experiment may be said to exist only to give the facts the chance of disproving the null hypothesis.”

If the facts fail to disprove the null hypothesis then I’m happy to call that a negative result.  People are free to try again and then I’ll look at the distribution of the results and make a judgement. 

To reduce the influence of bias associated with small trials, I’m not going to accept a result from a trial without at least 50 participants per group.  This is absolutely vital.  Trial size (actually the Standard Error) was shown by Shang et al (2005) to be the best indicator of bias in trials of homeopathy (P<0·0001): the smaller the trial the more positive the result; conversely large good quality trials of homeopathy tend to show that it is indistinguishable from a placebo. (A trend present in conventional interventions, with one major difference: the largest high quality trials still show a benefit relative to placebo.) 

Attrition rate is also important.  If 25% or more of the participants dropped out of the study before it was over, I will view the results with extreme caution – again, as advised by Bausell (2007). 

So, let’s filter the data and see what evidence is left. 

CAM Journals

CAM journals tend to report a higher percentage of ‘positive’ studies than reputable medical journals.  For this reason articles in these journals are best discounted as they are more likely to exhibit bias.  So, none of the following will figure in my final summary; but in the spirit of open enquiry it is interesting to see what evidence the CAM literature provides for treating hay fever with homeopathy. 

Aabel et al (2000) reported a small (n=66) double-blind, randomized, placebo-controlled trial, over a four-week period in May 1995, to assess the efficacy of the homeopathic preparation Betula 30c in patients sensitive to birch pollen: “No statistically significant difference between the groups was found during the first and last period of May”.  Some statistically significant differences were found “For some days”.  Given the number of outcomes measured over time and the failure to correct for multiple inferences: this can only be seen as temporal cherry-picking.  Aabel (2000) reported a small (n=73) follow-up trial performed the next year: it was negative.  

Colin (2006) reported a case series (n=147) for patients with respiratory allergy seen by a private homeopathic practice.  An 87.6% success rate was claimed.  In any event, this is not a useful trial design for evaluating efficacy. 

In a similar vein, Goossens et al (2009) undertook a, “prospective, open, non-comparative study” to evaluate, “quality of life after individualized homeopathic treatment for seasonal allergic rhinitis” and concluded that an RCT was required. 

No information was available on the article by Hubbard (1964).  It is unlikely to report a treatment trial. 

The paper by Launsø et al (2006) describes patients who had treatment for hypersensitivity illnesses by general practitioners or classical homeopaths and the patients’ self-reported effectiveness of the treatment received.  Both groups reported improved psychological health.  57% of the patients who visited a homeopath retrospectively reported improvement in their health, compared to 24% of those who consulted a general practitioner.  It is not clear to what extent this study looked at hayfever.  Importantly, the trial design does not permit an assessment of efficacy. 

Teut et al (2008) report a very small (n=11, verum and n=4, placebo), “randomised, double-blind, placebo-controlled trial” of a homeopathic proving of Galphimia glauca C12.  They reported no statistically significant differences between the verum and placebo groups; though did make some highly speculative claims.

 Weiser et al (1999) report a randomized, double-blind, equivalence trial (n=146) of the Luffa Heel Nasal Spray; they claimed that it was, “as efficient and well tolerable as the conventional therapy with ^**cromolyn sodium.”  It is worth noting that this product contains a number of constituents at the D4 potency – a dilution of 1 part in 10000.  This is a dilution level well below the so-called Avogadro limit; so the putative medicine is actually present.  This is not at all comparable to the more typical ultra-molecular homeopathic remedies. 

Wiesenauer and Heidl (1999) claimed to have, “evaluated the effectiveness and safety of a homoeopathic drug combination in the treatment of pollenosis under condition of daily practice.”  This was a very small trial (n=35) and did not include a control group of patients randomly assigned to an indistinguishable placebo.  On these grounds alone it is clear that the study design does not allow effectiveness to be evaluated.  In fact, the authors concluded, “Whether this improvement is due to the medicine or some other factor would need to be determined in a controlled trial.”  Quite. 

Even given the well-known failings of the CAM literature the evidence to support the use of homeopathy for hay fever is unimpressive.  It boils down to one reasonably sized trail which appears to show equivalence between a non-individualised complex homeopathic remedy with some ‘medicine’ in it and a conventional therapy, two small negative trials of Betula 30c and a failed but tiny proving of Galphimia glauca C12. 

Filling in the blanks

As noted earlier, some of the articles have little or no information available in English – so I’m not going to be able to scrutinise them.  Also, some caution is required when looking at trials not published in English (Vickers et al, 1998). However, an English summary is available for Wiesenauer et al (1983) and some additional data is available in the meta-analysis of Linde et al (1997). 

This study examined the effect of Galphimia glauca on pollenosis (hay fever) with a, “randomized, controlled, multicenter, and double-blind clinical trial” (n=86) that used a D4 potency.  They claimed that the treatment was, “more effective than placebo at a 1% level of significance” and quoted a success rate of 83%, compared to 47% for the placebo group.  

However, comparing the data in the summary with that provided by Linde et al (1997) reveals a 29% attrition rate.  In addition this same source calculates an odds ratio of responders vs. non-responders for ocular symptoms rated as relieved or much better after 4 weeks (on an intent to treat basis) at 1·94 with a 95% confidence interval ranging from 0·93 to 4·04.  This is, statistically speaking, a non-significant result. 

So, although Wiesenauer et al (1983) was published in German some key details are available.  Its language of publication can be taken as an indicator for potential bias.  Its high attrition rate is also too high.  Also the analysis by Linde et al (1997) adds a cautionary note.  Finally the use of a 1:10,000 (D4) dilution does mean that it bears little relation to many homeopathic interventions: there will be some Galphimia glauca in the medicine. 

Size Matters

Applying some basic quality criteria has whittled down the list to four trials of homeopathic treatments of hay fever, published in English and using an appropriate design. 

However Kim et al (2005) is small (n=40), with less than 50 participants per arm.  Also, as O’Mathúna et al (2005) pointed out: this was a trial of isopathy and used a 1 × 10^-6 (wt/vol) dilution of various pollens; a standard immunotherapy dose.  They also criticise the statistical methods used in the analysis, a point conceded in the authors’ reply (Riedlinger et al, 2005). 

Similarly, Taylor et al (2000) only included 51 patients with perennial allergic rhinitis, again less than 50 participants per group.  Also, for one of the two main outcomes measured – visual analogue scale scores – no significant difference was seen on average between the groups. 

This publication drew a good number of comments and criticism from correspondents.  Lipworth (2001) observed that the trial showed an, “apparent dissociation between objective responses to homoeopathy (domiciliary nasal peak flow) and subjective responses (nasal symptoms) after four weeks” and concluded that, “[…] a longer period of homoeopathy or a different dose” might have resolved this.  Also that, “we need to know how homoeopathy compares to conventional drug treatments such as intranasal corticosteroids and antihistamines, given their proved long term efficacy on symptoms in allergic rhinitis.” 

Miller (2001) contended that the statistical analysis used in the study was flawed.  In addition, Brown (2001) wondered whether the patients really had allergic rhinitis.  Windeler (2001) contended that, “the results were negative, the meta-analysis was (or may be) flawed, and there was no homoeopathy at all.”  Whereas Dean (2001) unconvincingly argued that double-standards were at work in the unfavourable view of homeopathy taken by many reviewers. 

Taylor et al (2001) defended their work.  They conceded that their study was underpowered but argued that this risked, “false negative results, not false positive results.”  In a theoretical sense this is correct.  However the analysis of Shang et al (2005) demonstrates that in practise the reverse is true.  Their response was dismissive of Windeler’s critique, but did not provide convincing counter-arguments. 

This paper also provided an ‘overview’ of previous trials undertaken by the authors.  I’m not going to peruse this further as the authors conceded that their analysis of this body of work was not a meta-analysis.  Although the authors argue that this is a coherent body of work and should be analysed as such, Windeler outlines a number of reasons that make any statistical treatment of the complete ‘dataset’ unwarranted.  The author’s reply signally fails to engage with these substantial criticisms. 

An interesting commentary by Lancaster and Vickers (2000) appeared alongside the article in the BMJ.  Here are some of their observations: 

“The current trial is the fourth in which this group evaluated a similar treatment, comparator, patient group, and outcome measure. As with the previous studies, the primary outcome used to calculate the sample size was a visual analogue score measuring patients’ perceived improvement in symptoms. In contrast to the earlier studies, they detected no effect of homoeopathic treatment on the visual analogue score. These data do not strengthen the conclusion that homoeopathy differs from placebo. In fact, the effect of including the current study in their meta-analysis with data from the three earlier trials is to weaken (though not overturn) this conclusion.” 

“The authors report a significant effect of homoeopathy on a second outcome measure, the nasal peak inspiratory flow. […] However, it is difficult to place this finding in the context of the previous studies as they did not measure this outcome.” 

“Because of the relatively small number of patients studied, neither the positive nor the negative result of the current study would shift this estimate significantly. To move the scientific debate forward, homoeopathic research needs trials with the power to detect or effectively refute the moderate effects suggested by the meta-analysis. Others have shown that such trials are feasible in homoeopathy.  The new challenge for Reilly and colleagues is to do the large trials that really could change thinking.”

Clearly, whatever the merits of the criticisms levelled at these trials, the key one remains: they are too small to be relied upon. (It’s also interesting to see that Lancaster and Vickers, along with Windeler, ‘mistook’ the statistical overview for a meta-analysis.) 

And Then There Were Two

That leaves only two reasonably sized RCTs published in English.  Of these Reilly et al (1986) compared the effects of a homoeopathic preparation of mixed grass pollens with placebo in 144 patients with active hay fever using subjective outcome measures.  Although it reports that, “homoeopathically treated patients showed a significant reduction in patient and doctor assessed symptom scores” this must be viewed with some caution:  according to Cucherat et al. (2000) it suffers form a high drop-out rate – 35%.

Finally, Wiesenauer and Gaus (1985) report a, “a controlled randomized strictly double-blind trial with 164 patients.”   This relatively large trial compared the effectiveness of homeopathically prepared (i.e. succussed) Galphimia D6, a conventional Galphimia dilution of the same concentration (1 part in 10⁶) and a placebo.   The difference between the homeopathic preparation and the placebo was not statistically significant, though they claimed a “clear trend for the superiority of Galphimia D6”.  This is a negative result; the 37% drop-out rate (calculated from the data provided in Passalacqua et al, 2006) also provides reason for caution in extracting any trends. 

Is That All There Is?

Applying some basic quality criteria has sifted the evidence down to a single, reasonably sized positive RCT and a single, reasonably sized negative RCT.  Both of these suffer from a high attrition rate.  This doesn’t inspire me to trust homeopathy or those who peddle it.

Looking at the evidence as a whole, my opinion has to be that that there is no credible evidence that homeopathy can help with hay fever.  The high-quality large-scale trials that would be needed to really demonstrate benefit, called for by Lancaster and Vickers (2000), have not been done.  If anything, the more recent work appears to show no progression in terms of quality or scale.  This gives me the impression that this is a field in decline.  Homeopathic advocates seem more enthusiastic about marketing its use for hay fever than showing it actually does any good. 

There is certainly not enough evidence, in my view, to support any clinical recommendation in favour of homeopathy.  Also, as a number of the trials combine homeopathy with conventional medication there is absolutely no justification for implying that homeopathy is any sort of alternative treatment. 

Anyway, that’s my view, but to make sure that I wasn’t being too harsh I decided to have a look at what the reviews that my search identified had to say. 

What the Reviews Say – Treat These With Some Caution

As with the individual trials, I’m not going to give any credence to articles published in the homeopathic fan-lit. (Hyland and Lewith, 2002; Mathie, 2003) 

Similarly, I approach reviews not published in English with some caution.  However, an English summary is available for Gamus and Kokia (2008).  They conclude that: 

“Several good quality trials in […] homeopathy have reported positive effects in allergic rhinitis and asthma. However, overall mixed results and methodological flaws, when analyzed by systematic reviews, lead to the conclusion that, as yet, there is insufficient evidence to reliably assess the possible role of these treatments for rhinitis and asthma.”  

This seems to be a fair summary of what I’ve found.  Similarly, a review which appeared in Prescrire international (2008) concluded that: 

“Despite evaluation in several randomised controlled trials, there is no firm evidence that homeopathic preparations have any specific efficacy in allergic rhinitis.” 

Lüdtke and Wiesenauer (1997) pursued the evidence for Galphimia glauca.  Their analysis included, “7 randomized double-blind placebo-controlled trials and 4 not placebo-controlled trials (1 randomized and controlled, 1 prospective uncontrolled, 2 retrospective uncontrolled) performed by our study group between 1980 and 1989. “

Including uncontrolled and un-randomised trials in a statistical analysis undermines the exercise.  Twenty-eight percent of the patients in this analysis were from these poor quality trials.  It does make me wonder whether the fact that this is the authors’ “study group” has skewed their thinking. 

Viewed in this light the main result: that self-assessed relief from, “eye-symptoms is about 1.25 (CI: 1.09 to 1.43) times higher in the verum than in the placebo group” is not very convincing.  The authors also note that, “As not all of the single studies were analyzed by intention to treat analysis the results may be biased.”

Bandoiler (2000) looked at this trial in detail and offered this “clinical bottom line”: 

“Galphimia glauca, D4 dilution […] is not very effective for the relief of ocular symptoms due to acute pollinosis. The NNT was 9.0 (5.2 to 31) on more than 500 patients. The NNT for the C2 dilution […] was 3.8 (2.6 to 7.0) based on a small number of patients. However, these trials have all been conducted by the same research group and to date have not been independently replicated. […] Trials all conducted by one study group are analysed and reviewed by themselves in this publication.”

More reliable views?

Kay and Lessof (1992) did not have much to say about homeopathy, but included it in the conclusion that: 

“[…] we have yet to be convinced by substantial evidence that any of the other alternative methods of diagnosing or treating allergic disease are of proven value. There have, however, been many false and misleading claims and serious harm may be caused by misdiagnosis or delays in appropriate treatment. The public should be warned against costly methods of diagnosis and treatment which have not been validated.”

Passalacqua et al (2006) observed that:

“Some positive results were described with homeopathy in good-quality trials in rhinitis, but a number of negative studies were also found. Therefore it is not possible to provide evidence-based recommendations for homeopathy in the treatment of allergic rhinitis, and further trials are needed.”

And finally Resnick et al (2008) omitted homeopathy from their assessments of CAM modalities with potential: 

“Efficacy of CAM modalities should be established with randomized, double-blind, placebo-controlled trials, including adverse-effects monitoring. Of all the CAM therapies examined to treat allergic rhinitis, some herbal therapies and antioxidants demonstrate a trend toward some clinical efficacy.”

 [Frew has been involved with several interesting looking reviews (Frew, 1994; Frew et al, 1991).  Unfortunately I’ve not been able to get hold of any copies so I can’t comment further.] 

Just to be fair…

Linde et al (1997) did provide a positive sub-analysis of trials involving the use of Galphimia glauca for pollenosis.  The outcome analysed was self-reported improvement in ocular symptoms.  I’ve discussed two of the four trials included (Wiesenauer et al, 1983; Wiesenauer and Gaus, 1985), the remaining trials are not listed in PubMed.  It is worth reflecting that Shang et al (2005) found that non-MEDLINE indexed trials tended to show a more beneficial effect for homeopathy than those indexed (p=0·019). 

I would argue that there are good grounds for viewing this result with some scepticism.  As Bandolier (2000) has shown, something like nine patients need to be treated for one to benefit significantly.  This is hardly impressive. 

It is also worth noting that even this faintest of silver-linings is tinged with material doses: the trials used potencies from D2 to D6.  Even if this review is reliable, all it does is provide evidence that actual doses of Galphimia glauca tend to make a few people feel that their eye-related symptoms have abated. 

Now I’m aware…

This exercise has certainly improved my awareness of the paucity of evidence supporting this year’s Homeopathy Awareness Week campaign. 

If you are prepared to accept the CAM literature uncritically and rely on a single study, then you may be persuaded that Luffa Heel Nasal Spray might do some good.  Of course it’s not classical homeopathy, it actually contains some of the stuff that appears on the label. Also, the allegedly vital aspect of ‘individualisation’ is missing. 

Putting aside any qualms about relying on the unreplicated work of a single “study group” the results for Galphimia glauca might persuade some to think that this sort of homeopathy may help.  Of course the evidence, such as it is, is only about how you may feel about any eye related symptoms.  Also, this intervention is based on actual doses of Galphimia glauca .  Again, this provides no support for the sort of homeopathy that relies on either the ‘law’ of infinitesimals, or stresses the importance of ‘individualisation’. 

Looking into the mainstream medical literature leaves homeopaths clutching at the much-touted work of Reilly et al (1986).  This exercise in isopathy stands in splendid isolation as a relatively large, positive, trial.  However, the attrition rate means it can’t be trusted. 

The conclusions reached by published reviews are lukewarm, to say the least.  With the glaring exception of the positive view of their own work taken by Lüdtke and Wiesenauer (1997) none of the reviews appearing outside the CAM literature go beyond asking for further research. So, there is no good quality evidence to support advising people to use homeopathy to treat hay fever; I would have hoped that medical doctors who practise homeopathy would know that.  

What does the BHA have to say?

On its website the BHA offers a document called, “Clinical research evidence in favour of homeopathy”:  by definition an exercise in cherry-picking. 

What does it say about hay fever?  It, apparently, lists eleven items of evidence, starting with some ‘systematic reviews’:  Bellavite et al (2006) just summarises the results obtained by Reilly et al (1986) and Taylor et al (2000).  Next, in a bit of double-counting Taylor et al (2000) is cited on its own.  The last review cited is Wiesenauer and Lüdtke (1996) which seems to be the same flawed review as Lüdtke and Wiesenauer (1997): the one that added in a decidedly material dose of 28% patients from uncontrolled trials. 

Next it lists RCTs, starting with Aabel et al (2000) – a negative trial.  Odd that the document counts it as evidence in favour; but, in keeping with the title of the document, the larger negative follow-up Aabel (2000) is not mentioned. 

The small high-dose isopathy trial of Kim et al (2005) is cited.  As is Reilly et al (1985), which I’ve not discussed here as it was preliminary to the next paper the BHA cite: Reilly et al (1986). 

Taylor et al (2000) makes another appearance: more double-counting. 

The concluding three citations are for the Luffa Heel Nasal Spray investigation of Weiser et al (1999) and two Galphimia glauca trials: Wiesenauer et al (1983) with its not very dilute dose (1:10,000) and  high attrition rate, along with an un-indexed paper^***(Wiesenauer et al, 1990). 

So, I count nine separate pieces of evidence.  One is actually negative.  The rest appear to have been selected with, as far as I can see, little apparent regard for quality:  classic cherry-picking. 

I cannot help but draw the obvious conclusion – that the apparantly respectable medical homeopaths are only interested in apparently positive results for their particular brand of paternalistic magic medicine. 

Would I trust in homeopathy for hay fever?  Not on this evidence.  On the whole, I would say that there is enough trial data to say that the incredible dilutions peddled by many homeopaths don’t work, and why should they?  Perhaps some of the less dilute interventions might – but more work is needed. 

So what does this make Homeopathic Awareness Week?  In my opinion, nothing more than a sales drive. 

Disclaimer

Please remember that I’m not offering you any medical advice!  If you need that consult a proper doctor. 

Notes

*If you don’t have access to this book, here is a summary of Bausell’s (2007) approach to assessing CAM trials. 

**cromolyn sodium is an interesting compound. An example of a herb-derived therapeutic agent, originally used for the management of asthma, it is also used to treat allergic rhinitis (hay fever). According to WebMD, “It may take 1 to 4 weeks before cromolyn sodium is fully effective. Because of this, cromolyn sodium is considered more useful in preventing allergy symptoms before they develop. It is not as effective as other medicines at treating symptoms after they have already started.” This might go some way to explaining the equivalence of the homeopathic intervention: the trial compared the efficacy of Luffa Heel and cromolyn sodium as a treatment for hay fever symptoms over a 42 day (6 week) period. It would seem that cromolyn sodium may not be expected, on the average, to be an effective treatment in the early part of the trial; and is more likely to be used as a prophylactic. Interestingly the UK NHS Direct website does not mention this drug as a treatment option. Could this be a false comparison: Homeopathy works as well as something that isn’t the best or most usual treatment?

***For the sake of completeness a summary can be found here.  It is light on detail, but the comment, “A total of 54 practitioners selected 201 patients for the study” makes me wonder about the method of randomisation.  As I’ve already pointed out, Shang et al (2005) found that non-MEDLINE indexed trials tended to show a more beneficial effect for homeopathy than those indexed (p=0·019). 

References

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Edits

16^th May 2009. Note on cromolyn sodium added. Some minor typos and glitches in the links to references corrected.

[BPSDB]