A shaky start

The introduction is peppered with frank errors, for example that very large clinical trials are incapable of identifying the causes of diseases. They are not designed to do that! Then, I came across the term `orthomolecular medicine’, which is megadose vitamin therapy by another name. This is the obsession which Linus Pauling developed in his later years, and is seen by most nutritionists as overt quackery. The foreword is written by perhaps the leading quack from the field. This man says that evidence based medicine claims to provide certainty about treatments. If he knew the tiniest thing about it he would know that there are no certainties in science or medicine.

Clearly Hickey and Roberts do not understand what evidence-based medicine (EBM) is, or how it is used. They witter on ad nauseam about the problems with epidemiological evidence, but they do not know that randomised controlled trials are not epidemiology. There is a long and tedious section about `proof’. These two can’t have spoken to any EBM researchers, or if they did they are ignoring what they heard. We do not talk about `proof’, all we do is obtain the best evidence we can, always understanding that it might be changed by later and better research. How facile and idiotic it is to say that you can’t select clothes for people by averaging their measurements! They are either being deliberately obtuse, or they really are stupid. EBM works by providing evidence of what is most likely to be effective treatment, and that information is taken into account when obtaining as much information as possible about the individual patient. But the authors get this wrong, by saying that EBM claims certainty. It does not. They say that the best information comes from the patient, but how on earth is the doctor going to select a treatment solely from the information they get from the patient? I have yet to see them answer that, or even ask the question. The patient is not going to tell them what antibiotic works for the infection they have. I laughed out loud at the bit about blood pressure. They seem to think that doctors are going to give the entire population antihypertensives! They claim that no `epidemiological’ trials have ever been shown to save lives. But they seem to be talking about large scale intervention trials (epidemiology is not interventional), and there is not a shadow of doubt that some of these have shown reductions in mortality. If they think large scale randomised controlled trials are useless, then they can forget about receiving any effective treatment when they get cancer. Mortality from cancer in young people has been halved in the last 40 years.

In bed with the usual suspects?

I realised that this book could not be taken seriously, when the authors exhorted the role of complementary and alternative medicine (CAM) practitioners. These are people who mainly lie to their patients about how the body works, and give treatments which have either not been tested, or (mostly) have been tested and do not work. For example, acupuncturists say the body is pervaded by a life force which travels along `meridians’ they have found on the body. Chiropractors say the life force travels along the spine. Can they both be right? No, they are both making it up.

There are no plausible proposals in the book for replacing EBM. The authors make the mistake that analogies are OK for explaining an argument, but they don’t necessarily prove the point. They like exposing what they think are fallacies, but fall victim to the false analogy fallacy. However I have now found out what drives their vitriolic attack. They had a spat with the US National Institutes of Health some years ago, about orthomolecular medicine (AKA megadose vitamin therapy, qv), a thoroughly discredited brand of quackery as we know. Hickey and Roberts display all the attributes of the `prophet crying in the wilderness’. This vitamins saga crops up repeatedly, so they are obviously smarting over it. I just came across a reference to Dr Devra Davis and her book The Secret History of the War on Cancer. I did a little research on Dr Davis – yes, she is another conspiracy theorist, who has been raking over the mobile phone and cancer canard.

Hickey and Roberts trot out a litany of EBM abuses, but do not realise that when people fail to follow the EBM model, they do not invalidate it. Time and again we are told that it’s wrong `arbitrarily’ to discard data. They do not seem to know that selection of studies for meta-analysis and systematic review (they don’t appear to know the difference) is very far from arbitrary, but based on quality. As information specialists they ought to know about signal to noise ratio. There is a vast amount of noise in medical data, because humans are complex and we can’t possibly know all that is going on inside them. By rejecting poor quality studies we reduce the noise and hence make the signal easier to spot. They present meta-analysis as a way of gerrymandering the data to get statistically significant results. In my experience it is just as likely to show the opposite, that there is nothing happening. In some fields there are several studies with unclear and conflicting results, and a meta-analysis can show that taken together there is no treatment effect. That’s what you get with homeopathy. Of course, the authors don’t like that sort of outcome, and make some barbed comments about sceptics.

While Hickey and Roberts appear to know how a sample size is calculated, they don’t understand how it is used in practice. A key input is the expected difference between treatments, which has to be justified by prior information. For a phase I study, that would come from animal studies. It might be modified by what is known about similar drugs to the one under study, eg we might have reason to believe that our drug is better than established treatment so we would expect a bigger difference. Now they are great fans of Bayesian statistics, and there is nothing wrong with that per se, but as with the conventional (frequentist) approach which I have just outlined, the Bayesian approach relies on what is called the prior probability. That has to be justified as well – you can’t pull a probability out of the air. The tragedy for these two people is that, if they did that for their beloved orthomolecular medicine, they would get a prior probability of zero as there is no evidence that it works.

I will concede that the authors are right about trials getting much bigger, and they are right about the common mistake of quoting relative risk instead of absolute risk. But the latter abuse is perpetrated much more by the lay media than by researchers. Journalists can write a story about a mortality reduction of 50%, but not about a fall from 1% to 0.5% (they are the same thing).

They say that EBM ignores case reports. No, no, no. Case reports and in particular case series are useful indicators of whether there is a phenomenon that should be formally investigated. Where there is doubt however, case reports on their own are of very little value.

They seem so obsessed with their own cleverness that they fail to spot the obvious. Do they not know that the BMJ paper about the lack of randomised controlled trials (RCTs) for parachutes was a seasonal joke? The point is that RCTs are only required when the outcome at issue is in doubt. Nobody needs an RCT for splinting broken legs. Similarly, they don’t realise that the website about the Daily Mail’s twin obsessions with things that cause cancer, and things that cure it, is a jibe against tabloid journalism and not against EBM.

An `ideal’ non-EBM study

There is a curious section about a `simple Bayesian study’ of diabetes drugs conducted by `Dr Carlos’, a primary care physician. The authors claim that using this approach, with a very small number of patients, the doctor will be able to predict the correct treatment for the next patient. I have taken advice from two statisticians, Dr Adam Jacobs and Dr Alastair Knight, and the pharmacologist Professor David Colquhoun who has written a statistics book. Here is our collective assessment.

The authors say nothing about what prior probability is used for the Bayesian calculation. They are testing the difference between drugs, so they should estimate the probability of there being a difference. However if they have no good reason to believe A is better than B (or vice versa), it would be a uniform (uninformative) distribution, ie prior probability of zero. In that case, Bayesian calculations give you exactly the same result as conventional statistics.

The authors call this an ideal Bayesian study and highlight the supposed benefits of this design over EBM, by which they presumably mean a frequentist approach. However the authors fail to recognise the fact that Bayesian study designs can be included in EBM assessments and meta-analyses of the like. Furthermore the statement that “Dr Carlos can immediately see the likely benefits..” highlights the authors’ disregard for statistical interpretation. They fail to explain how he can do this, and the fact is that he can’t. This approach is no better than the conventional one.

The point seems to be that the authors claim a Bayesian analysis has all sorts of advantages over a more traditional frequentist analysis. To be fair, they provide a graph of the probability distributions which is a reasonably good way of visualising the results. However, talking about the normal way of presenting the results as being “gobbledygook” seems unjustified. You could easily present these results as a risk ratio or a risk difference, with confidence interval. The risk difference could, if wished, be converted to the number needed to treat, which is a pretty intuitive way of presenting the results.

The bit which is most egregious nonsense is the statement “Bayesian statistics are not highly sensitive to the experimental conditions”. If you do a flawed study, then you’re going to get flawed results whether you analyse them in a frequentist or Bayesian way.

We are not trying to argue against Bayesian statistics. They certainly have their place, and in some places can provide a much more intuitive way of looking at things than frequentist statistics. We’d probably be using them a lot more were it not for the regulators’ reluctance to believe in them. But to pretend that it’s somehow something different from “EBM” is nonsense. It’s just a different way of analysing the results.

As stated above, their approach adds nothing to the conventional approach. You could construct distribution curves for the actual observed values of a properly designed study – ie with continuous data rather than this arbitrary dichotomous outcome they have used here (Dr Carlos’ categories of `responder’ and `non-responder’). That would give at least as much information as they have here.

They keep saying that data from large clinical trials can’t be used to predict the response of individual patients, and that this is an example of the ecological fallacy. Now that says that you can’t say draw inferences about an individual by deriving summary data from the population of which the individual is a member. Their example is that you can’t average shoe sizes and say that’s the size for anyone in the population. The first mistake here is that CTs don’t even try to say anything definitive about any patient, they simply estimate the probability of the response you might get. As people who go on at such length about probability distributions you would think they would know that. Next, they put together this tiny study by `Dr Carlos’ and say that from the responses seen in the patients so far, they can predict the response of the next patient. So they are deriving definitive data about the next patient from all the ones seen so far. Or, if they defend themselves by saying that they are only predicting the probability, then they are doing exactly the same as a normal CT, but more weakly.

The ecological fallacy is about making inferences about individuals from populations. You might, for example, say that the French drink a lot of wine and have a low incidence of heart disease, and conclude that wine therefore reduces the risk of heart disease. That’s fallacious (despite probably being true anyway!) because we don’t know whether the specific French individuals who live to a ripe old age with healthy hearts are the same ones who are drinking a lot of wine. However, in a clinical trial, the situation is completely different. In a randomised trial of X vs placebo, we know that the individuals in the placebo group got placebo. We don’t see how they could claim that clinical trials are subject to the ecological fallacy without talking bollocks.

And yes, you can’t predict with certainty what will happen to an individual patient based on conventional clinical trial data. But you equally can’t do so based on a Bayesian analysis. The only way you could make predictions for individual patients (and of course this is starting to happen as part of the trend towards “personalised medicine”) is to collect a lot of data on patient characteristics, biomarkers, etc, and use them to define which patients will respond to a specific treatment and which won’t. And then, of course, you still can’t predict with certainty, although you can certainly improve the odds.

Back to megadose vitamins

A bit later there is a long section on their favourite topic, megadose vitamin C. I will keep my comments about that short. The evidence they cite goes back to Dr Fred Klenner in the 1950s, who claimed to have treated polio successfully. The authors claim that the results were replicated, but all of this evidence appears to be case reports, ie it is anecdotal. There is a lot of bleating about how expensive it would be to run the huge study that would satisfy the EBM crowd, but my question is this. Why has nobody carried out the small cheap Bayesian study that Hickey and Roberts were extolling earlier in the book? There has been no attempt by any of the megadose vitamin proponents to do any randomised comparative study on any scale, however small. The entire argument relies on anecdotal evidence. Hickey and Roberts also argue for focussing on effects that are obvious and don’t require huge studies to detect small effects. They say the effects of megadose vitamin C are dramatic. So why no study designed on that basis? Do they protest too much?

A major theme is that EBM is selective, and that ALL the data must be used to make decisions. Yet at the end they recommend a kind of informed guesswork, heuristics, which exposes a further conflict in the authors’ minds. This they say is an effective way to make medical decisions, using minimal data. Well it can be – triage can be heuristic-based. But how does this fit with their obsession with accepting all data? It makes no sense.

Another repeated mistake is that Bayesian statistics are anathema to EBM. This is rubbish. They can be used in EBM, and are, but the regulators are conservative and it’s hard to educate them. But of course, while Hickey and Roberts think they understand Bayesian stats, they don’t really understand how to use them, as we saw from the `Dr Carlos’ trial.

The obsessive objection to large scale trials belies what actually happens in drug development. The pathway starts small, very small. After studies in healthy volunteers to get initial assessments of safety, pharmacokinetics etc, studies of typically 100 patients are carried out to test whether the drug actually has a clear effect. This is the sort of `sticks out like a sore thumb’ test that Hickey and Roberts recommend. They don’t appear to have noticed that it happens already, and has done for decades. After that stage, much larger studies are carried out to confirm that the effect is real. Even those need further support from studies which are more representative of the population seen in clinical practice. Quite often, the large studies fail to show anything useful – the reverse of the authors’ claim that big studies are designed to mislead us by detecting insignificant effects.

The authors include a huge number of references, but a great many are misquoted and misinterpreted, by my quick reckoning. Many references are to books and speculative review material by others, rather than to rigorous science.

These authors seem to be well trained and experienced in science, but they are not by any means the first to go off the rails and pursue madcap ideas. Isaac Newton spent more time on astrology, alchemy and religion than he did on physics and maths.

The saga of Dr Stanislaw Burzynski and his antineoplastons (ANPs) is in danger of turning into a soap opera. Well actually it probably already has, as it has gone on for decades with no real plot and no end in sight. Many bloggers have been as puzzled as I as to why the US regulator, the FDA, allows this to continue. Admittedly, from time to time the FDA takes some sort of action, but it is never decisive – he is always allowed to carry on charging desperate patients vast sums to receive an unproven drug. First, let’s look a little more at what is happening here in the UK. I am indebted to Liz Woeckner of Citizens For Responsible Care and Research, who has identified at least 10 British patients who have travelled to Burzynski’s clinic in Houston, started treatment, and then returned home with supplies of antineoplastons (ANPs) in their luggage – apparently complete with IV administration sets. Liz has also compiled a pack of documents obtained form the FDA under Freedom of Information requests, which demonstrate the long history of serious regulatory violations at Burzynski’s facility. I’ll leave you to digest that lot.

Well, here is the list of UK patients that we have collated so far:

Luna Petagine (Raglan Gardens, Oxhey): http://www.lunapetagine.co.uk/diary

Amelia Saunders (Reading, Berkshire): http://www.ameliasmiracle.com/2.html. Note that Burzynski’s `exemption’ trial (ie patients could be treated outside an approved protocol) closed in 2006, and this patient was born in 2008 so must have been treated under an approved protocol.

Billie Bainbridge: http://www.billiebutterflyfund.org/billies-story/

Claire Faulkner: http://www.clairefaulkner.co.uk/

Hannah Bradley: http://teamhannah.com/

Laura Hymas: http://www.hopeforlaurafund.co.uk/

Chiane Cloete: http://helpmefightcancer.co.uk/

Supatra Emily Adler: http://supatrascancerfight.blogspot.com/p/home_10.html

Gus Lilly: http://web.archive.org/web/20110203164359/http://guslilley.com/

Andrew Sherwood: http://www.thesherwoodfoundation.org.uk/Home: Site has now been taken down.

Once I had this list, my first question was: if these patients are all taking ANPs (and apparently under FDA approved protocols), have UK physicians obtained ethics approval? Let me remind you that worldwide all clinical trials of investigational drugs must be reviewed by an independent ethics committee, and must have approval from the national drug regulatory authority. Not only does the ethics committee review the protocol, it also must review all patient-facing documents, including any advertising for recruitment to the study. That would include any websites.

Joan Kirkbride, Director of Operations, National Research Ethics Service, told me:

We have searched our database using the search terms: antineoplastons; A10 (Atengenal, Cengenal); AS2-1 (Astugenal, Fengenal) and Burznyski and have not returned any results.

“However Dr Burznyski would not be permitted to be a Chief Investigator for a trial in the UK as he is USA based and it is a requirement that such a person be based in the UK.

“My understanding is that there are other mechanisms to provide investigational medicinal products outside a clinical trial protocol eg for compassionate use but the MHRA would be able to provide further information in this regard.

Now hang on a minute, there are these trade names Atengenal and Cengenal. While surfing with those names, I also came across another one, Astugenal. Two of these, Atengenal and Astugenal, are being actively marketed by a California company Pediatrica USA, but not to US consumers. The company “acts as a patient’s representative so that these experimental yet potentialy (sic) life-saving drugs may be made available to developing countries. US residents cannot use this website.” Needless to say, the company operates in association with Burzynski. I would really like an expert oncologist to review the material on this site, in particular the descriptions of the mechanisms of action. But whether or not there is substance to the claims, the scenario is clearly one of exporting an investigational drug without a full dossier on efficacy, safety and quality. Is it not interesting that `developing countries’ are targeted? Would it not be more lucrative to export to say the EU? But of course, it also has tough regulatory legislation. The export drive is set out in this SEC filing, which lists the countries involved, and for which this contract engages a marketing company, Carigen.

I also spoke to the UK regulator, the MHRA, and learned that there had been no submissions for regulatory approval for ANP studies in the UK. I had already checked the EudraCT database and found nothing, although this is notoriously incomplete. The fact remains that if certain UK doctors are involved, they are not simply prescribing an unlicensed drug, they are acting as investigators for a drug classified by the FDA as in development.

I had another go at the FDA about these UK patients, but the reply (from the Center for Drug Evaluation and Research) totally avoided the question, and simply reiterated that ANPs are investigational drugs. Although I didn’t ask about illegal promotion, I did get this:

The FDA has sent an Untitled Letter to The Burzynski Research Institute (BRI) and The Burzynski Clinic for promotional and marketing claims about the safety and efficacy of its antineoplastons, investigational new drugs that have not been approved by the FDA.  The unapproved promotional claims made by BRI violate the Federal Food, Drug, and Cosmetic Act (FD&C Act) and FDA regulations. The promotion of investigational new drugs is prohibited by law and the agency is concerned BRI’s promotional claims will mislead patients about the safety and efficacy of the unapproved antineoplastons.  FDA plays an important role in ensuring sponsors provide accurate information about their investigational drug products to patients and health care professionals.

FDA requested that BRI submit a written response to the Untitled Letter by November 1, 2012, stating whether BRI intends to comply with FDA’s request that it cease the dissemination of violative promotional materials for antineoplastons, and explain its plan for discontinuing use of such violative materials. We are currently reviewing BRI’s response. Because this is an open case, we are unable to share additional information at this time.

That was on 7^th November 2012 (sorry, there is so much stuff that this post took a long time!). Others I think have already picked up on the FDA’s warning letter, referring to this earlier website and also to the Burzynski Research Institute site. The two sites appear to have removed all promotional claims, but the Burzynski Clinic site still links to the patient group site, where you can find all the usual hyped-up claims.

Naturally I pressed CDER for an answer about exporting ANPs, and was simply referred to the legislation. It seems impossible to get a direct answer. But from exports, we move to imports, or the lack of them. This import refusal was issued by the FDA over two years ago. It appears that Burzynski was trying to get ANPs made abroad.

The FDA seems to be under fire from both sides. The patient groups constantly press for immediate approval of ANPs, as exemplified by this package sent to the Clinton administration (shows how long this has been going on). Look at page 31 – the FDA quite rightly refused to consider a submission for marketing approval from a single investigator.

Well this is a rather disparate collection of facts, but it reflects the vast complexity of Burzynski’s operations. To boil it down to essentials, there must be some UK doctors under whose care patients are receiving ANPs, and it’s not clear whether the imports and exports of ANPs are lawful. So far we have one name, Dr Simon Berrisford, cited by the parents of Burzynski patient Andrew Sherwood (site taken down as noted above). I do not know any more than that, indeed I do not know Dr Berrisford’s role, and I would not presume to ask him to breach patient confidentiality. But I am still curious as to what his role is. If he is operating as a co-investigator of Dr Burzynski, then he needs approval from a UK ethics committee and from the MHRA. There are no records of those approvals. If he is not operating as a co-investigator, then research data on an investigational drug are not being collected, as required by the FDA.

I have been looking at Burzynski’s study protocols, cached here. I am way out of date it seems – we have here 72 protocols listed. At www.clinicaltrials.gov there are only 62. Burzynski gives his protocols internal numbers, which don’t appear on clinicaltrials.gov, so it’s extremely difficult to work out whether we are talking about the same studies. However to take one example at random, protocol BT-7 is entitled “Antineoplastons A10 And AS2-1 In Patients With Glioblastoma Multiforme”, and was dated originally 1996. On clinicaltrials.gov study 60 has the same title, and is stated to have started in 1998. My suspicion is that here we have a bizarrely large number of studies, which are created to accommodate whatever patients come through the door (look at the vast range of conditions), and go on for decades. If that is not the case, I’ll be perfectly happy to publish a correction, but it’s up to Burzynski to show how I am wrong. Note the large number of changes to this protocol logged on clinicaltrials.gov, over the period June 2005- August 2008. Most of these are trivial, but I did notice that in 2007 the primary study indication was changed from “Recurrent Adult Brain Tumor” to “Brain and Central Nervous System Tumors”. This is quite unusual in my experience, and again suggests that protocols are being customised to suit patients.

I was deeply shocked by this paragraph in the informed consent section of protocol BT-14:

If your child is injured as a result of participation in this treatment, emergency care will be made available by the hospital and billed to you as part of your medical expenses. No financial consideration or compensation will be provided for a research related injury.

I have never heard of any such clause in any study, let alone receiving ethics approval. All clinical trials of investigational drugs are required to have insurance in place against drug-induced injury. This protocol is about as unethical as it’s possible to get. We already know that the institutional review board (IRB – or ethics committee in European parlance) is attached to the Burzynski Research Institute. Indeed it is called the Burzynski Research Institute IRB. It is quite clear that this IRB does little or nothing to protect patients. We also know that it received a damning inspection report from the FDA in 2008, but when I asked the FDA whether that had been closed out I got the usual stone wall. But again CIRCARE has the story. Some 10 months after the inspection, the FDA issued a warning letter, in October 2009. There is nothing on public record since then.

I have also been looking again at the investigator site inspection which the FDA carried out in 2001. Note that this was a `directed’ inspection, what we call these days `for cause’. It must have been in response to something that raised their suspicions. A possible cause could have been the detailed report published in The Cancer Letter in 1999, reproduced at QuackWatch with permission. Worth reading if you have the time. Anyway, here are the warning letter, the inspection report, and Burzynski’s response. The heavy redactions are of course excessive, and reflect the US obsession with secrecy. Note that item 6 of the warning letter states that Burzynski failed to include mandatory wording in the informed consent information. This demonstrates that ethical review is essential, and that it simply wasn’t happening. So far, I have been unable to identify any further action from the FDA, but as a clinical research professional here are my observations:

1. The inspection report shows that Burzynski was at that time very clearly an incompetent investigator. International standards for Good Clinical Practice (GCP) say that everyone involved in clinical trials must be qualified by education, training and experience. Burzynski is not a board certified oncologist, which I would have thought was essential for what he is doing (I looked on the Texas Medical Board database). Why has he not been listed by the FDA as a debarred investigator?
2. There is no mention anywhere of independent study monitoring. This is frankly baffling. It is a GCP requirement that three roles are in place, sponsor, investigator, and monitor. The last is normally carried out by a clinical research associate (CRA), who does inter alia the checking of case report forms versus source documents. They also check drug accountability, another major violation at the site. Obviously nobody was doing that, yet the FDA did not ask who should have been doing it. At inspections, it isn’t mandatory for the CRA to be present, but the documents on site must include a log of monitoring visits carried out. The inspector should check those to ensure the visits did happen. Everything checked by the CRA should have a signature to verify they did it. There’s not a word about any of this in the report.
3. None of the documents includes the letters from the FDA which Burzynski claims give permission to treat patients off-protocol. I think it is very important to clarify what is going on here. If there is no such permission, then GCP applies to everything he is doing, wherever it is in the world.
4. The FDA inspection report mentions that Burzynski was charging patients for ANPs. Yet they don’t list this as a violation. So why mention it? They seem to think it was unusual. The clue may be that the matter doesn’t come up in the warning letter, most likely because the FDA was not confident that such an allegation would stand up in court – in the light of Burzynski’s track record through the courts.

This post could easily go on for another four pages, so I think I need to stop here and let you assimilate it. More to come.

STOP PRESS! Just saw the post from Josephine Jones that suggests the BRI studies are on clinical hold. No point in asking the FDA for more news of course, we’ll have to wait and see. A while back I asked readers to press the FDA to inspect Burzynski, and now it seems they are. But I am intrigued as to the legality of suddenly shipping a vast load of ANPs to this patient – for which presumably they will get a huge bill.

Here’s an excerpt:

600 people reached the top of Mt. Everest in 2012. This blog got about 7,500 views in 2012. If every person who reached the top of Mt. Everest viewed this blog, it would have taken 13 years to get that many views.

Click here to see the complete report.

Thank you for your letter dated 7 November 2012. The issues raised by Mr Goldacre (sic) in his book, Bad Pharma, are important and we take them very seriously. I would like to add that during the development of Mr Goldacre’s book, the ABPI did try on numerous occasions to make contact with Mr Goldacre and we were disappointed that he did not respond. Consequently, there are a number of issues that we are now clarifying through public debate.

I wish to reiterate, as outlined by the ABPI on 5 October 2012, that the pharmaceutical industry is one of the most highly regulated industries in the world. The industry has stringent and robust transparency requirements and disclosure of all data exists in line with international standards set by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), as well as a host of other regulatory bodies, both national and international.

However, although I believe the pharmaceutical industry sets a very high standard on protocol, disclosure and transparency, we do recognise that there is always room for improvement and refinement. The UK and the ABPI has often led the debate on transparency and has undertaken extensive work in this area. The ABPI’s CEO, Stephen Whitehead, is a major champion of transparency and the ABPI reaches out and listens to all stakeholders on such debates, however difficult that may be.

In the UK, the ABPI has been doing considerable work through its ethical working group consisting of the Royal Colleges, the BMA and The Lancet. Only six months ago, the ABPI and the BMJ hosted a joint conference on this very issue to understand exactly what stakeholders want from the industry and what we, within the UK, have the power to influence.

To this end, the ABPI is committed to further improving the research and development process. This should be through stakeholder engagement involving all those working in R&D, regulation and healthcare delivery while ensuring that we put patients at the heart of everything we do so that they continue to have access to new and innovative medicines.

I hope this addresses your concerns. Please do not hesitate to contact me should you have any further queries.

Yours sincerely
Deepak Khanna
President

Of course, I took up his offer to request further information, and asked when and how the alleged attempts to contact Ben were made. There was no reply, so I tried again. I then received an email, which got me all excited, but it contained no text, only a PDF attachment. This was another letter on ABPI stationery, which said:

Please contact my colleagues at the ABPI head office, who will be happy to assist you with your query.

The same letter then arrived in the post, in a nice high quality envelope. An amazing effort in order to say nothing of any use. In fact I had already phoned the ABPI press office to ask the same question, but so far there has been no reply, even after two phone calls and three emails. This is all very interesting in view of Ben’s perspective on it. He says:

They made absolutely no attempt to contact me whatsoever. That is very simply another false claim from the ABPI.

It is extremely puzzling behaviour, especially since they have also told other people that they are deliberately not engaging with me. I think this does a great disservice to the many ethical professionals in the pharma industry.

What more can I say? This is the industry that I have been proud to serve over nearly 40 years. There is a large majority of ethical professionals in it, and they will be as disappointed as I am. Ben says to contact him if you have anything else on this: ben@goldacre.net

In my early years on the commercial side, of course I was trained to present clinical evidence in the best possible light. Does anyone remember the recession of 1975 or thereabouts? A certain marketing department invented the disease ‘economic malaise’ for which a certain tricyclic antidepressant was highly effective (allegedly). At another company, we had a non-steroidal anti-inflammatory in a crowded market. It was known within the company as ‘a salesman’s product’ as it was tacitly admitted to be no better than the competition. Indeed the sales force was trained to minimise its shortcomings. However some of the reps were not so easily convinced by the weak clinical studies with which they were armed. The company did invest in more ‘research’, but for this product only in uncontrolled studies designed to ‘seed’ the product among GPs.

Another time, I was told that I needed a ‘passion for the product’. This is something that needs to be understood. No enterprise can really succeed without people to champion what it is doing. In this sense, marketers are no different from scientists. We all have our enthusiasms, we all need something to get us out of bed in the morning. Hence, we are all susceptible to biasses born of emotion. It’s important to accept this, and to consider how to handle it for the common good.

Well that was decades ago, and nothing like that happens now. Or does it? The difference is that Big Pharma is rather more subtle these days. But not so subtle that companies don’t sometimes get caught out, and I have recently addressed elsewhere the cases of Roche and Glaxo SmithKline. In my 25-year life of consulting for Big Pharma, I have more than once had to tell clients that what they were doing was against my professional advice regarding regulatory and/or ethical compliance. A commonly contentious issue is interpretation of data. I remember having a considerable battle over a safety study, from which the company was determined to derive an efficacy message – when efficacy was not even in the protocol objectives. Many years ago, I worked in a medical department which operated largely as a branch of sales and marketing. I did me no good to point out the constraints of the industry code of practice.

But I do hope that Ben’s book doesn’t lead the reader to believe that all of Pharma is Bad. I’m told that there is substantial discussion of safety data reporting. To quote from chapter 1:

You only have to tell the regulator about side effects reported in studies looking at the specific uses for which the drug has a marketing authorisation.

He also says that there is no need to tell the regulators about safety data from trials that take place outside the EU.

From this, it looks as if there are huge regulatory gaps in reporting adverse events. There may be gaps, but they are not for want of trying to close them. For the uninitiated, let me outline some of the legal requirements for clinical trials.

An adverse event in a clinical trial is defined as any unwanted change in the patient’s condition, and must be reported. Note that the question of causality is immaterial to the question of whether the event should be reported. If a meteorite fell out of the sky and squashed the patient flat, that would be an event (certainly adverse) that would have to be reported.

In addition, this tragic event with the celestial body would also qualify as a SERIOUS adverse event (SAE). Such events include what some of you might consider fairly humdrum, such as any unscheduled hospital stay. SAEs are subject to expedited reporting, which means they must be reported to the sponsor and the regulatory authority within very strict time limits, not just at the end of the trial. Overall, every adverse event, serious and non-serious, must be reported to the regulatory authority in the final report.

There is a further category of adverse event, called in the EU a SUSAR. This is a serious unexpected suspected adverse reaction. Note that now we are considering causality, and there are clearly defined criteria for that, set out in the trial protocol. But even if the event doesn’t qualify under those criteria, the doctor doing the trial can decide that the study drug might have caused the event, independently of the sponsor. Now all SUSARs are not only subject to expedited reporting to the regulators, as are all SAEs, but they have to be reported to all the other investigators in the trial, wherever they are in the world. Those investigators have to sign to say they have received and read the reports, and they then have to send them to the ethics committees which approved the trial at their institution.

I have described here only a very small part of the process for safety data monitoring in clinical trials. Vast armies of people labour away in drug companies, poring over streams of SAE reports, checking that they are complete (they rarely are), and repeatedly chasing the investigators for corrections. It is such a huge and complex operation that I am surprised it works as well as it does. Sadly, sometimes it goes badly wrong. There are no excuses, it has to get better, as Goldacre has quite rightly pointed out. But I and several colleagues are at a loss as to how he has derived the statements above.

So I hope you can understand my dismay at the manner in which the UK industry has responded. When I joined my first pharmaceutical company in 1974, I pretty quickly realised that the ABPI was a largely toothless watchdog. It hasn’t improved noticeably in almost four decades. I’ll leave you to read their response, but suffice it for me to say that dismissing Goldacre’s arguments in a few words, and then writing several paragraphs on how wonderful the industry is, doesn’t actually address the points at issue.

There are many people who would like us to believe that prescription drugs do more harm than good. The evidence gives the lie to that. There are many studies which clearly show that, if you can get patients to take their medicines, you save money. A good deal of the evidence comes from the USA, where the health insurers and managed care companies (for all their many faults) have an avid interest in reducing costs. For example, the Asheville Project showed that if you get patients to comply with their prescribed treatment, you reduce overall health care costs  - and where drugs cost twice as much as they do in the UK. This would not be happening if the drugs didn’t work.

So knowing what I do about Big Pharma, and from the inside, I am sure that Bad Pharma is a worthwhile and necessary book. The industry is not quite as bad as Goldacre says, but it’s nowhere near as good as the ABPI seems to think. I won’t enjoy reading it, but I feel I have to.

Please provide the reference(s) for the following publication(s):

All studies demonstrating efficacy of antineoplaston treatment, submitted by The Burzynski Research Institute, and/or Dr Stanislaw Burzynski, and/or The Burzynski Clinic, in support of the application to proceed to phase III clinical trials.

Please note that, as approval for phase III has been granted by the FDA, and there is now an obligation to publish hypothesis-testing research, it is to be expected that the information I have requested will have either been published, or is pending publication. If the latter is the case, please state where publication will take place.

I received an acknowledgement via snail mail dated 9th February, and nothing after that until I started chasing last week. The US FOI Act has the same 20-day response benchmark as ours does, so this was a long way over. The request was passed from pillar to post until it arrived on the desk of Ms Lee, who emailed me and asked me to phone her. Here are some highlights of the conversation.

EL: This is a complex request. Have you made previous FOI requests to the FDA?

Me: No, not previously.

EL: Well complex requests normally take 18-24 months for a response.

Me: Excuse me, but what is complex about it?

EL: A simple request is something that is already available, that we would pull from our databases, in a short amount of time. The FDA is not able to confirm or deny the existence of any information on new drug applications, or to confirm the status of new drug applications.

Me: What puzzles me is how the FDA has allowed at least 61 `trials’ to be conducted, without showing any evidence of efficacy. My understanding is that in order to get into phase III one would have to show some efficacy from earlier phase studies. Is this information you can’t give me?

EL: (Long pause): Erm – we can’t discuss drug research prior to approval of the drug.

Me: You do realise of course that this drug has been investigational for over three decades?

EL: I understand…..

Me: So this could go on indefinitely?

EL: I can’t speak to that unfortunately.

Well you get the drift. The conversation went on like this for several minutes more, with every question stonewalled. So let’s summarise:

• The FDA has been approving clinical trials which don’t meet the most basic of scientific standards (that the FDA would demand of drug companies).

• The FDA does not consider that charging desperate people huge sums for an unproven treatment is unethical.

• The FDA is not worried about non-compliance by the Burzynski Research Institute’s institutional review board (ethics committee) and the Institute itself, because it has not closed out the warning letter. Note that I regularly get notified by the FDA of regulatory action being taken against other IRBs and investigators.

• The FDA has given approval for a phase III trial but refuses to justify that approval.

The FDA has used the `complex request’ option to block this request. In fact it is not complex at all. The FDA has given phase III approval, and will have issued that in writing to the applicant. The document is readily available. It is curious that the FDA is trying to use two ways of blocking this request. One is that it’s a `complex request’, which it isn’t, and the other is that all information prior to drug approval for marketing is confidential. My guess is that they are using the first in order to defend their failure to reply within 20 days, and the second as `belt and braces’.

But I am of course not sufficiently familiar with US law, and would value contributions from American friends. There is something very odd going on here.

But it seems that you can set up a charity to do almost anything you want. The Commission defines charities as “voluntary organisations which benefit the public in a way the law says is charitable”. What is not defined is how they assess benefit to the public. I will take as examples two charities that have caught my attention recently, The Maun Homeopathy Project and CancerActive.

The first of these horrified me. Africa has quite enough of a problem with HIV and AIDS, without deranged quacks distracting poor and vulnerable people with unproven `remedies’. OK, there is nothing that I can find at www.homeopathybotswana.com to suggest that patients are being taken off proper treatment, or that homeopathy is being offered as a cure for AIDS. All that I have read is entirely compatible with any benefit being related to counselling and not from homeopathy. Some would say this is acceptable, and a useful role for placebos. I say that the last thing Africa needs is another dose of superstition and quackery – it has more than enough of those. The greatest gift we can offer emerging countries is that of education and knowledge. This charity is offering the opposite. It is rather reminiscent of tobacco companies, who find very limited sales growth in developed countries and are turning to the third world to recruit more victims.

So I reported this to the Charity Commission, on the basis that there was no public benefit. Needless to say my complaint was rejected – here is the reply:

Thank you for your e-mail.

I am sorry to learn of your concerns about the charity.

However I have examined your comments and would conclude that this is not an issue we can become involved in. We are unable to intercede in a difference of opinion relating to the validity or otherwise of medical ethics.

I would add that The House of Lords Select Committee determined that Homeopathy is a ‘Group 1′ therapy. Charitable organisations that provide therapies that fall within the Group 1 category of ‘well known’ therapies do not generally need to provide further evidence of efficacy before we accept that these therapies are effacious (sic) in the relief of illness.

The Maun Homeopathy Project is established for the following purposes;

‘To relieve sickness and distress and protect and preserve health, particularly but not exclusively of the people of Maun, Botswana and surrounding areas, who are suffering from HIV and AIDs and the trauma of rape by the provision of homeopathic health care with the object of improving their conditions of life and their physical and well being’

The charity specifically states that is does not provide a cure and this can be viewed using the link below:

http://www.homeopathybotswana.com/what-is-homeopathy/

Charities are independent organisations, and their trustees are legally responsible for all aspects of their management and administration.

Complaints about the treatment methods vaunted by a charity should be addressed to the trustees in the first instance. Contact details can be found on our website:

http://www.charitycommission.gov.uk/showcharity/registerofcharities/registerhomepage.aspx?&=&

We would always encourage charities to have appropriate procedures for dealing with complaints about their services and to respond to complaints in a timely manner. However, ultimately this is an aspect of the administration of the charity which is the responsibility of the trustees.

If there were evidence that the charity was causing serious harm to beneficiaries we would investigate the organisation further, however, it would be unfair to act on unsubstantiated allegations or opinions which could disrupt a charity’s work.

Thank you for bringing these matters to our attention. I hope that I have explained why the Charity Commission will not be taking any further action.

I trust this information is of some assistance to you.

I suppose I should not expect an administrator in a public quango to have much understanding of evidence, but this does cause me some concern. My allegations are apparently `unsubstantiated’. Well the position as to evidence for homeopathy is hardly unsubstantiated, and the charity openly admits to giving it to poor people in Africa. Then, what I say is apparently `opinion’ – as usual the writer can’t tell the difference between opinion and evidence. Yes, I really do want to disrupt the charity’s work!

I put this on the back burner, but then was even more incensed by the claim from the notorious Cancer Active that “homeopathy reverses cancer”. This clearly breaches not only the standards for a charity, but most likely the Cancer Act 1939. So in went another complaint. This time I got a more extensive reply, as follows:

Thank you for your email dated 22 March 2012.

Thank you for contacting us recently and raising your concerns about Cancer Active. We have looked carefully at the information you have provided and appreciate the time you have taken to send this to the Charity Commission.

Our publication Complaints About Charities (CC47) explains in detail what issues we can look into and how to let us know about them. This can be downloaded from our website:

http://www.charitycommission.gov.uk/Publications/cc47.aspx

We have assessed your complaint in relation to the criteria that are set out in our published guidance. I am writing to explain that the Commission does not consider that the complaint falls into the category of complaints that we take up and therefore we will not be taking any further action.

When we receive a complaint that has been assessed as not meeting our criteria, we will keep the information on record and acknowledge your complaint, but will not take any further action.

Making a complaint about a charity

We receive a number of different types of complaints about charities, but there are only certain kinds of complaints we can get involved with. Essentially, we want to know if there is a serious risk of significant harm to or abuse of a charity, its assets, beneficiaries or reputation and we will take action if our intervention is a necessary and proportionate response to protect them.

However, we have found that the majority of complaints we receive should be made directly to the charity itself rather than the Charity Commission. These complaints include ones about the services a charity provides, employment issues, fundraising methods and internal disputes.

The concerns that you have raised are not matters that the Charity Commission can offer advice on because they are not within our regulatory role. It is important to emphasise that although the Commission’s functions include encouraging and facilitating the better administration of charities, and taking remedial action to tackle misconduct or mismanagement, the law prohibits the Commission from acting directly in the administration of a charity. Trustees are the managers of their charities and it is their job to make the administrative and strategic decisions necessary for their charities’ proper and effective management.

The important point to note here is that any decision with regard to the content of a charity’s website has to be taken by the trustees. The Commission cannot direct the trustees to take one particular course of action or another. Neither does the Commission have discretion to overrule the trustees’ validly taken decision on the grounds that others take a different view, however strongly held.

Given that your concerns are not within the regulatory role of the Charity Commission we will not respond to any further correspondence from you on this issue. You can find further information about our regulatory role on our website.

I hope that I have explained why the Charity Commission will not be taking any further action.

Note the warning that they are not going to respond to me again about this. However there is more to it than even the staggeringly dangerous `advice’ that this charity provides. It is operated by one Chris Woollams MA (Oxon) (the usual paid MA I suspect). He shamelessly includes a link to his Natural Selection Shop, which I am sorry to say sells products from the arch-quack Joe Mercola (he of FDA warning letters that he wears like badges of honour, eg this, and this). Let’s look again at the Charity Commission site – they say that one of the issues they want people to tell them about is “charities deliberately being used for significant private advantage”. I can’t think of a better example than this, a charity blatantly linking its website to a business, and even promoting products on the charity’s site.

But there’s more. Woollams’ business is actually called Chris Woollams 4 Health Ltd, a company registered in the British Virgin Islands. Now why the British Virgin Islands, a well known (former) tax haven? The company claims it is not for profit, and then says “Any profits we do make will go to a Foundation, set up to help people with cancer”. So does it make profits or not? Why does it need to be registered offshore? Where and what is this `Foundation’?

Woollams’ business links with the charity are not confined to his online shop. The latest accounts for Cancer Active make interesting reading. Income for 2010-11 was £205,509, a substantial amount for a small charity. Of this, £86,714 came from sale of products, for at least some of which (as we have seen) excessive claims are being made. I am not even sure whether sale of products is allowed, bearing in mind the charity’s stated aims. But I am slightly more interested in the amount of £25,397 owed to Health Issues Ltd (see section 8 Creditors). What is Health Issues Ltd? It appears to be involved in publishing. According to Companies House, its directors are Jane Reynolds and Lindsey Fealey, but more to the point a past director who resigned in 2010 was one Christopher Woollams. By this time you might have guessed that both Cancer Active and Health Issues Ltd are registered at The Elms, Radclive Road, Gawcott, Bucks, MK18 4JB – and you would be right.

The other odd thing is that Chris Woollams is not a trustee of Cancer Active. The three trustees are Larry Brooks, Elaine Tipton and the aforementioned Lindsey Fealey, who is given on the Charity Commission website as the main contact, not Chris Woollams as per the Cancer Active site. Of course, trustees are not allowed to profit personally from a charity – do you see a pattern forming here?

Well the Commission refuses to listen to me about this, so what about a concerted effort from some of you good people? Just go to the Charity Commission complaints site and state that Cancer Active is failing to operate for the public benefit, and is being used for business purposes. Please note that you don’t have to go through the first step of complaining to the charity, because using it for private advantage is considered a serious issue.

Meanwhile, I have also reported Cancer Active to Trading Standards which notes that products are being promoted, so that puts the charity within their remit.

Section 14b of the draft guidance states:

“In providing care you must…. Provide effective treatments based on the best available evidence.”

However the guidance does not define what evidence is. As such, it is likely to cause confusion among doctors and among the public. There are many registered doctors who administer treatments on the basis of anecdotal and other poor quality evidence. Very occasionally, these doctors have been disciplined by the GMC. I envisage in future such doctors being brought before the Fitness to Practise panel, and engaging in convoluted arguments to the effect that they used the best available evidence, even though that evidence did not meet the accepted `gold standard’. The GMC needs to make clear its expectation in this regard. I therefore propose expanded wording as follows:

Doctors must provide effective treatments based on the best available evidence. Where the evidence is inadequate (for example where high quality clinical trials have not been published), doctors must be prepared to justify their choice of treatment when challenged, taking the risk:benefit assessment into account. Where there is significant evidence that shows a treatment to be ineffective, doctors should not use the treatment.

In all cases, doctors must effectively inform patients as to the evidence available for the treatment prescribed, and informed consent must be documented.

Evidence must be taken to include:

1. High quality randomised controlled trials (RCTs). Quality must be established by a recognised grading scale (ref).
2. Systematic reviews and meta-analyses.
3. Other research which demonstrates generalisability to normal clinical practice, but only when underpinned by RCTs. For example uncontrolled observational studies are useful as an adjunct to RCT evidence.

Evidence that relies solely on anecdotes (ie patient testimonials), poor quality RCTs, uncontrolled studies, patient surveys, and similar non-rigorous studies, must not be used to justify a treatment choice.

These provisions apply to treatments where the outcome has previously been in doubt. For example, the efficacy of setting broken bones is not in doubt, and does not require RCT evidence.

Reference

Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clin. Trials 1996; 17: 1-12.

I have not said it explicitly, but I have taken it as read that doctors must not knowingly prescribe placebos. I think this is fairly well established anyway.

If you haven’t responded yet, do so now – you have until Friday 10th February (2 working days from the date of this post). You will need to register, but it’s a very quick process.

Yes, it’s an answer, but to the wrong question. I have to say that the author Janet Woodcock did a pretty good job at telling the Burzynski sycophants to get lost,which is fine as far as it goes. What I want to know is why the FDA allows a medical scam to continue.

So I thanked Karen for her reply, and pointed out the error. Indeed my original questions were still at the bottom of her email in reply, so I just told her to scroll down. Since then she has said that she has to consult with colleagues, and they still haven’t got back to her – that’s as of 20:00 UK time on 14th December.

Now what is rather annoying is that Dr Lewin, who is responsible for regulatory compliance by clinical researchers, has passed this on to what appears to be the news desk. She has obviously not followed up on the questions that I and many others have asked her. I am clearly not getting very far with the news desk, so I will email Dr Lewin again and set out the questions in bullet points. OK I am not a US citizen, but this issue has a big impact in the UK so there is public interest over here. Her address is constance.lewin@fda.hhs.gov.

However, can any readers who are US citizens please take up the baton? Let’s have lots of you good brave Americans pressing Dr Lewin for answers. Can you lobby your democratic representatives? I for one am not going to be brushed off, and neither should you.

Craig comes across as well read, as he ought to as a university professor, but doesn’t convey to me any fundamentally new concepts. He starts with a wild claim that religious belief is undergoing a resurgence, quite the opposite of my understanding. He says that 30% of philosophy professors are theists, which is hardly relevant to whether any god exists. The people who know how the universe works are scientists not philosophers, and he doesn’t mention them in this context. It’s very well documented that almost all top scientists are non-theists, a fact he ignores. The significant point is that, while religious belief runs at about the same level in all scientists as it does in philosophers, among the most accomplished scientists (ie the ones who know the most) only 7% are believers. Of course, Craig’s gambit is really the discredited `appeal to authority’, but here he has chosen the wrong authority.

His philosophical rhetoric sounds impressive, but throughout he never addresses the matter of evidence. His attempt to poke holes in theoretical physics misses the point totally. The undisputed fact that current theories are incomplete does not in any way strengthen the argument for a god. Does he not understand that the nature of science is the crash testing of ideas? Necessarily there will be lots of ideas and they won’t all, indeed can’t all, be right.

Religious historical figures get lots of coverage, especially Thomas Aquinas. I have studied the latter’s `proof’ for the existence of God and found it logically weak, as again it depends on internal relationships between a set of concepts and doesn’t reach out for evidence (that has been said to be its strength!). Indeed I have just read the `proof’ again and, rather than a tour de force in logical reasoning, it now presents itself to me as remarkably stupid. Aquinas deliberately constructs a contradiction in order to dismiss the possibility that God might not exist.

To recruit William of Occam to Craig’s cause seems a bit cheeky. OK, Occam was a Franciscan monk but however unlikely current theories of the universe are, Occam’s Razor would surely cut out the possibility of the even less likely God? I did warm slightly to his critique of the evolution of many universes, but this must be among the most speculative of concepts and not supported by anything we have observed.

Craig is correct that science is rooted in the concept of causality, but we have to remember that the arrow of time is something that we have deduced because of the way the universe works now. If, as many cosmologists agree, both time and space came into being at the Big Bang, then at that instant there was no arrow of time and no causality as we know it now. It seems crazy to me to try to apply present day concepts to such alien conditions. Time is essentially inseparable from entropy – the only way we can measure time is by reference to it. When entropy achieves its maximum, that will literally be the end of time. At the Big Bang, entropy had not started so there was no time, and hence no causality.

But Craig departs even further from logical thought with his arguments about plausibility. Yes, our universe is extremely implausible, but surely a personal creative intelligence is even less plausible? He falls into the standard believer’s trap of assuming that the deity is beyond challenge or questioning. He makes no attempt at all to speculate as to why his god should ever exist. Had he done so of course, he might have been forced to ask why this god would have created the universe. Was it for the god’s own amusement? If so, he has a strange sense of humour, as he has ever since presided over one horrible natural disaster after another, presumably because he made such a poor job of designing the universe (I am only using `he’ by convention). It seems that Craig’s obsession with causality stops here. This failure makes his discourse appear even more pretentious than it might have done.

Overall, Craig seeks to get the scientific ducks in a row and knock them down one by one, until all that is left is his god. His mistake is in thinking that science is complete, and that there are no more ducks.

It appears that Dennett was given very little time to reply. Even so, I think he could have done a better job. He was more generous to Craig than I think was necessary, but he ended on an important note. He says that whatever we discover to be the truth, it will astound us. We should not speculate on what that truth might be, by applying our preconceptions and prejudices.

Now there are sceptics who refuse to debate with Craig, and for very good reasons. Craig believes in the literal truth of the Bible, for a start. That seems a very odd thing for a philosopher to do. For example, Richard Dawkins discusses at length Craig’s endorsement of the Israelites’ genocide against the Canaanites. It is a truly horrible and disgusting tale, and firstly Graig accepts it as true (it could well be), and secondly justifies it with arcane arguments. He even goes to the unthinkable extent of approving the slaughter of young children. Can the millennia of conflict in the Middle East be at all surprising when there are thought leaders like Craig endorsing massacres on a huge scale?

Such stories paint a picture of Craig as a player of philosophical games, without any personal connection to the claims of religion to provide a moral framework. Indeed, his pronouncements on the Israelites give the impression of a very unpleasant person indeed. I don’t expect him to challenge me to a debate, and if he did I would expect him to win on a point-scoring basis, but I don’t think I would want to be in the same room as him let alone on the same platform.