Just why is ‘pioneering’ cancer treatment so expensive?

A heartstring-tugging appeal in the NZ Herald doesn’t tell the full story.

Jesse Bessant is a little boy from Auckland with a very rare brain tumour. He has a ganglioglioma, a tumour that arises from ganglion cells in the central nervous system. As these tumours are very slow-growing, and with the location of his tumour (close to his brain stem) making surgery very risky, Jesse’s doctors have advised a ‘wait and see’ approach. However, the Bessant family have opted instead to try the Burzynski clinic in Houston, Texas, where Dr Stanislaw Burzynski offers his ‘pioneering’ antineoplastin treatment.

The catch? It’s going to cost the Bessants $375,000 to join one of Dr Burzynski’s clinical trials. The family’s fundraising appeal was covered by the NZ Herald in early March under the headline: “Hope for toddler with rare tumour”.

So what are antineoplastins and why is a clinical trial at the Burzynski clinic so expensive? Let’s start with those ‘pioneering’ antineoplastins. Might they be the next big thing in the treatment of cancer? I’m afraid to say that this is unlikely, as it turns out that Dr Burzynski has been trialling antineoplastins for over 35 years and has never produced strong evidence that his approach actually cures patients or increases their chances of long-term survival.

In fact the results of his trials don’t seem to have been published in the peer-reviewed medical literature and the American Cancer Society has gone so far as to recommend that people don’t spend their money on antineoplastin therapy. Dr Burzynski coined the phrase to describe a group of peptides that he identified first in human blood and then in urine and which he claimed to be “natural, non-toxic compounds that cure cancer”.

It turns out that the peptides can also be made by the body metabolising the drug sodium phenylbutyrate, which is how Dr Burzynski has been administering them for several decades now. Rather alarmingly, each 500 mg tablet of sodium phenylbutyrate contains approximately 62 mg sodium, meaning there is considerable risk of side effects including lethargy, weakness, irritability, seizures, coma and even death.

So if antineoplastins are just the by-product of sodium phenylbutyrate, why are Dr Burzynski’s clinical trials so expensive? After all, patients don’t usually have to pay hundreds of thousands of dollars to join a clinical trial. Sometimes they might even be reimbursed for taking part! It turns out that Dr Burzynski doesn’t just treat patients with his ‘antineoplastins’ anymore. Instead, he seems to be exploiting a very legitimate trend in real cancer therapy, often referred to as personalised medicine. Here patients are tested for particular disease markers which have been shown to respond to specific therapies. Orac, of the Respectful Insolence blog, has described Dr Burzynski’s “Personalized Gene Targeted Cancer Therapy” approach as “throwing everything but the kitchen sink” at the tumours. In fact, Dr Burzynski’s personalised therapy is part of a complaint against him by the Texas Medical Board, which is currently awaiting a hearing date. The complaint describes Dr Burzynski’s treatment of a patient with metastasised breast cancer, which included prescribing sodium phenylbutyrate with another four very expensive immunotherapy agents, none of which are approved for the treatment of breast cancer, and in combination with a chemotherapy agent.

In fact, it also transpires that Dr Burzynski owns the pharmacy that supplies the drugs he prescribes. His pharmacy is also accused of overcharging for drugs. A former patient, Lola Quinlan, has filed a lawsuit, claiming Dr Burzynski swindled her out of nearly $100,000 by using false and misleading tactics, including charging $500 per pill for drugs that could be bought elsewhere for a fraction of that price. And as well as the cost of drugs, there are his consultation fees, listed on one potential patient’s blog as:

  • Review of medical records prior to commencing treatment – $500
  • Initial consultation appointment – $1,000
  • “Genetic Tumor Markers” test – $4,000
  • Monthly treatment fee (with treatment suggested to last 4 to 12 months) – $4,500 – $6,000

All of which might explain why Dr Burzynski lives in a mansion with his initials in gold on the gates! But none of this was covered in the NZ Herald article. Don’t those being asked to donate deserve to know where their money is going? Instead, my emails to the journalist remain unanswered and Letter to the Editor unpublished. And the Bessant family continue to raise funds to send their child to be treated by a man who is accused by the Texas Medical Board of “unprofessional or dishonorable conduct that is likely to deceive or defraud the public or injure the public”. Pioneering? More like profiteering, if you ask me.

Amber teething beads: something to chew on

A ‘natural’ way to manage teething pain has no plausible mechanism.

Parents, especially new parents like myself, are a vulnerable group. We tend to be full of anxiety that we are doing the ‘right thing’ by our children. Wherever you find a vulnerable group like this you also tend to find those who prey on such fears.

Being a new parent and a skeptic I have been on guard regarding dubious advice and practices, but so far I have actually been pleasantly surprised: I have not, as far as I’ ve noticed, been subjected to any dubious advice. But recently I was confronted by a practice of a fellow new parent that I found a little disturbing. I’ m taking about using necklaces of amber beads to reduce the pain of teething for babies.

Teething can be an especially stressful time for parents and children. The child may be experiencing pain as the new teeth break through the gums; this means an irritable child and frazzled parents. Anything that promises to relieve or prevent this harrowing time is gratefully embraced.

On to the amber beads. This practice disturbs me for several reasons. First is safety. The necklace, if left on the baby for long periods, may pose a strangling hazard if it becomes caught on something. Most advertise that they are made to break easily to prevent this and that the beads are individually knotted onto the necklace to prevent scattering on breakage. However, this still seems to leave a broken string of beads in reach of a baby, and as most people know – anything a baby can get its hands on goes straight into the mouth. So choking is also a concern.

Now, I’m not one to be a worry wart over every little potential hazard; used correctly under parental supervision I suspect that the likelihood of a tragedy of this kind is low. But not zero. This, coupled with the low probability that the necklace actually does anything, is what worries me. The second disturbing thing is that parents are accepting that the necklaces work via word of mouth, and apparently not consulting their doctors before subjecting their child to an intervention of unknown safety and efficacy.

I have three main points I believe parents should consider before trying these beads (in addition to the physical safety above). The first relates to basic plausibility. There are several explanations for how the beads are supposed to work floating around the intertubes, many of the tinfoil hat brigade variety ([… it generates pain relieving magnetic field[). Only one explanation I have found makes biological sense so that’s the one I’ll be focusing on.

Baltic amber is known to contain between three and eight percent succinic acid. According to proponents this is released from the beads and into your baby. The succinic acid then allegedly has an analgesic effect and so reduces the pain of teething. Here is where my first point regarding plausibility comes in.

Amber is tough. Really tough. This is a material that has persisted for thousands and in some cases millions of years unchanged. Suffering through innumerable climatic cycles of heating and cooling. Yet this same tough unchanging material will happily give up its chemical components upon the gentle heating it receives on being placed next to your baby’s skin? Colour me unconvinced. I found a 2010 paper on volatile degradation products from Baltic amber that doesn’t mention succinic acid as an identified component. Related to this point, amber has a hardness on the Mohs scale of between 1 and 3. Baltic amber, which is usually touted as the therapeutic variety (because of the high succinic acid content), is at the high end of this scale at 2 – 2.5. To put this in perspective, Tin has a hardness of about 1.5 and Gold is 2.5-3. But let’s say for argument’s sake that clinically relevant amounts of succinic acid are released by the amber and absorbed by your baby’s skin.

My second point then, relates directly to the claims made for succinic acid. Succinic acid is made in the body (and in plants) as part of the citric acid cycle (aka the Krebs cycle). It is also used in the food and beverage industry as a food acid (additive #363 to be precise). Interestingly, in this capacity there are recommendations from some quarters to avoid the substance ([avoid it, banned in some countries[, warnswww.foodreactions.org).

Even so, apart from its early use as a topical treatment for rheumatic pain, there is no evidence that I could find (searching Pubmed at least, where I would expect a decent study to be referenced) that it is effective as either an anti-inflammatory or general analgesic. Let me be clear on that. I don’t mean low-quality evidence, I don’t mean small, poorly designed trials with equivocal effects, I mean nothing. Zip. Nada. In fact if anyone knows of any let me know because I find this complete lack quite surprising. I’m open to the idea that I was looking in the wrong place or was using incorrect search terms. So, unless there is late breaking news, it fails on that count as well. But what do we care about evidence of efficacy anyway? Let’s throw this point out too, and move on to my final point to consider.

Let’s say that (a): the beads do indeed release succinic acid into your baby and (b): this succinic acid has an analgesic effect once it enters your baby’s body. Doesn’t the very fact that an unknown amount of a drug is being put into your baby’s body bother you? (If it has biologic activity that can be used in a therapeutic fashion, it’s a drug, no quibbling on that point please.)

What is that I hear? It’s natural? Oh, well, that’s okay then. No wait, it’s not. I don’t care what the origin of a compound is, the question is what are its effects on the body and do the benefits outweigh the risks. Let’s replace succinic acid with some other naturally occurring substance, salicylic acid. This is a compound with known anti-inflammatory properties. Would you be happy with a product that introduced unknown levels of this compound into your baby? What if I said that overdoses with this compound could lead to a one percent chance of death (emedicine.medscape.com/article/818242-overview#a0199)? It’s natural; it’s also the precursor to acetylsalicylic acid, otherwise known as Aspirin.

Now, lest I be accused of unnecessary fear-mongering and drawing false comparisons I would like to admit that at present there is no evidence to suggest that succinic acid is hazardous, nor even that it is potentially hazardous. This does not detract from my main point however. It isn’t whether this particular compound is safe or not but that the reasoning around its use (ie [It’s got to be good, it’s natural[) is faulty and cannot be used as a substitute for evidence.

Based on the complete lack of plausibility on any level of efficacy any potential for harm, however small, must tip the balance of the equation away from the use of this product. But don’t trust me; talk to your doctor. I suspect though that given the complete lack of reliable information on this topic they will be left to rely on their own philosophy of harm vs benefit. In the final analysis, there are not always clear answers, but developing good critical thinking skills will at least provide you with a small light in the darkness.

The (bad) science behind the MMR hoax

The world-wide panic over the MMR vaccine was sparked by the actions of one doctor who breached several standards of scientific practice. This article is based on a presentation to the 2010 NZ Skeptics conference.

Every few years, the World Health Organisation (WHO) publishes a series of ‘death tables’, a summary of how many people died in a given year and the causes of death. The tables make interesting reading. The figures published for 2004 show that a third of all deaths worldwide were due to infectious diseases, a staggering 15.1 million people1. Of these, four million may have been prevented by vaccination.

As a microbiologist, I am staggered by the growing anti-vaccination movement. Vaccination has to be the success story of ‘modern’ medicine. Just look at the benefits: vaccination can provide lifelong protection, does not rely on correct diagnosis or treatment being available and can avoid some forms of auto-immune disease that can be triggered by infection. As the saying goes, prevention is better than a cure. While it is true that vaccines are not 100 percent risk-free, the benefits to both the vaccinated individual and the wider community (through ‘herd immunity’) far outweigh the risks.

What is fascinating about vaccination ‘hysteria’ is that different countries have different scares, even though they are using the same vaccines. One such scare, which has resulted in a resurgence of measles in a number of countries, relates to the MMR vaccine. This is a freeze-dried preparation of three living but disabled viruses: measles, mumps and rubella. In the 1990s, a British doctor by the name of Andrew Wakefield claimed there was a link between MMR vaccination and autism. He claimed to have discovered a new syndrome, which he called autistic colitis, in which autistic children were found to have a particular kind of gut disease.

He also claimed to have found that the appearance of symptoms of autism coincided with MMR vaccination, and children with autistic colitis had measles virus in their guts. His findings were based on a study of 12 children with developmental and intestinal problems, published in the Lancet medical journal in 19982. Nine of the children were diagnosed with autism. The children were believed to have been developing normally and then suddenly regressed, and parents were asked to recall how close to the time of MMR vaccination the symptoms appeared.

The study suffers from a number of crucial flaws, not least the lack of blinding or control groups, or potential for parents to incorrectly recall the appearance of symptoms. It also turned out that Andrew Wakefield had numerous conflicts of interest: he was receiving money from lawyers looking to build a case against a vaccine manufacturer, had submitted a patent on an alternative measles vaccine, breached ethics compliances and even paid children at a birthday party for donating blood.

The journalist Brian Deer was instrumental in bringing all of these conflicts to the public’s attention and has maintained a website (briandeer.com/mmr-lancet.htm) summarising his investigations into Wakefield and the MMR debacle. Recently, the British Medical Journal (BMJ) commissioned Deer to write a series of articles summarising his findings3-5. In 2010, Andrew Wakefield was found guilty of misconduct and struck off the medical register in the UK and the Lancet finally retracted his paper.

In an editorial accompanying one of Deer’s articles, the BMJ’s editors asked:

“What of Wakefield’s other publications? In light of this new information their veracity must be questioned. Past experience tells us that research misconduct is rarely isolated behaviour.”

What of his other work? Indeed, the Lancet paper was just the first in a series of papers by Wakefield attempting to link autism with measles. One of the things he showed was that measles virus could be detected in the guts of autistic children using a technique called the polymerase chain reaction (PCR). PCR is a fantastic technique used to amplify very small amounts of target genetic material to generate over a billion copies. In a nutshell this means PCR can take something that is undetectable and make it detectable. However, one of the downsides of such a sensitive technique is that it is very easy to contaminate, so proper controls are really important. For those who want to know how PCR works, there are some very nice videos online (youtube/eEcy9k_KsDI).
One of the crucial things needed to carry out PCR is a set of very specific ‘primers’ which recognise the region of genetic material that you want to amplify (Fig 1). You need primers to each end of the region of interest and then PCR amplifies the bit between the primers. So if the primers match the wrong region, you will end up with a large amount of the wrong thing, a classic case of garbage in, garbage out. So the important things to remember are:

  1. The primers need to be specific so that they only amplify what you are targeting and nothing else.
  2. You have to be very, very careful not to contaminate the reaction.

To make sure the primers are specific and nothing has been contaminated, it is crucial to include a number of controls alongside the samples being tested:

  1. A negative control which has water in place of any target genetic material which will tell you whether you have had a contamination problem or not.
  2. A negative control which has control genetic material that does not contain any of the target sequence which will tell you if your primers are specific enough.
  3. A positive control which has genetic material that does contain the target sequence which will tell you if your reaction has worked.

So, you have your samples and your controls, the PCR machine has done its dash and you are left with a little tube filled with billions of copies of the target sequence (or none if the sample was negative…). This can then be visualised by gel electrophoresis and you are left with something like the picture in Fig 2.
Lane 1 contains a size standard, lane 2 is the negative control containing no genetic material, lane 3 is the negative control containing no target sequence (the very faint band is just the background genetic material), lane 4 is the positive control containing the target sequence and lanes 5 and 6 are our unknown samples (which in this case are all positive). It is important to say here that very rarely would you see an actual gel published in a paper. Most results are just described as the number of positive or negative samples. This is important as it leaves the reader assuming the correct controls were done. But it doesn’t end with gel electrophoresis. To make absolutely certain, the amplified genetic material can be sequenced to confirm it is the correct thing. And if the claims you are making are wide-reaching and/or controversial then sequencing is exactly what should be done.

Andrew Wakefield hypothesised that exposure to the measles virus in the MMR vaccine was a factor in the emergence of his so-called ‘autistic colitis’ and that genetic material from the measles virus would be found in patients with the disease but not healthy controls. He supervised PhD student Nick Chadwick to investigate. The first paper they published (in January 1998) was in the Journal of Virological Methods, reporting a “rapid, sensitive and robust procedure” for amplifying measles RNA6. In August 1998 they published a second paper describing the use of the procedure to look for measles virus in samples from patients with inflammatory bowel disease (IBD)7. They state:

“These results show that either measles virus RNA was not present in the samples, or was present below the sensitivity limits known to have been achieved”.

They then went on to look at the children reported in the, now retracted, Lancet paper (that is, the ones with ‘autistic colitis’). Wakefield never published these results but Nick Chadwick did write up his PhD thesis in 1998. Brian Deer has put the relevant information from the thesis on his website (briandeer.com/wakefield/nick-chadwick.htm). Nick Chadwick concludes: “None of the samples tested positive for measles, mumps or rubella RNA, although viral RNA was successfully amplified in positive control samples”. Despite this negative result from 1998, Wakefield then appears as senior author alongside a team of Japanese researchers in a paper published in April 2000 in the journal Digestive Diseases and Sciences8 where they report the detection of measles virus:

“One of eight patients with Crohn disease, one of three patients with ulcerative colitis, and three of nine children with autism, were positive. Controls were all negative. The sequences obtained from the patients with Crohn’s disease shared the characteristics with wild-strain virus. The sequences obtained from the patients with ulcerative colitis and children with autism were consistent with being vaccine strains.”

In 2002 Wakefield then published another, bigger study of children suffering ‘autistic colitis’ with a team from Ireland9. They reported:

“Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients.”

Yasmin D’Souza and colleagues at McGill University in Canada published a very nice study in 2007 in which they compared the primers used by both the Japanese and Irish groups with their own primers for the measles virus on a range of IBD and control intestinal biopsy samples10. Any positive samples were verified by sequencing.

And the results? The primers used by Wakefield and colleagues weren’t specific for measles virus. In fact, the amplified fragments were found to be of mammalian origin. What this means is that human samples should all be positive. Unsurprisingly, when D’Souza tried using genuine measles specific primers they “failed to demonstrate the presence of MV [measles virus] nucleic acids in intestinal biopsy samples from either patients with IBD or controls”. They also failed to find any measles virus in samples taken from over 50 autistic children11. This does suggest that Andrew Wakefield’s research conduct does not stop with the Lancet study.

There is now a huge body of evidence indicating that there is no link between vaccination and autism. Despite this, Andrew Wakefield is held up by many as a hero, fighting a corrupt system with the ‘evil’ pharmaceutical industry at its centre. Wakefield has recently published a book entitled Callous Disregard: Autism and Vaccines – The Truth Behind a Tragedy. One reviewer wrote:

“Dr. Wakefield sets the record straight. It was not he who showed callous disregard towards vulnerable, sick children with autism. It was the British medical establishment, the General Medical Council, the media and the pharmaceutical industry that threw the children under the bus to protect the vaccine program. This is a book for everyone who cares about our future”.

Who needs evidence, hey?

References

  1. WHO website. www.who.int/healthinfo/global_burden_disease/en/
  2. Wakefield AJ, Murch SH, Anthony A, et al. (1998). Lancet 351(9103): 637-41. RETRACTED.
  3. Deer B (2011). BMJ. 342:c5347. doi: 10.1136/bmj.c5347.
  4. Deer B (2011). BMJ. 342:c5258. doi: 10.1136/bmj.c5258.
  5. Deer B (2011). Secrets of the MMR scare. The Lancet’s two days to bury bad news. BMJ. 342:c7001. doi: 10.1136/bmj.c7001.
  6. Chadwick N, Bruce I, Davies M, van Gemen B, Schukkink R, Khan K, Pounder R, Wakefield AJ (1998). Virol Methods. 70(1):59-70.
  7. Chadwick N, Bruce IJ, Schepelmann S, Pounder RE, Wakefield AJ (1998). J Med Virol. 55(4):305-11.
  8. 8. Kawashima H, Mori T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A (2000). Dig Dis Sci. 45(4):723-9.
  9. 9. Uhlmann V, Martin CM, Sheils O, Pilkington L, Silva I, Killalea A, Murch SB, Walker-Smith J, Thomson M, Wakefield AJ, O’Leary JJ (2002). Mol Pathol. 55(2):84-90.
  10. D’Souza Y, Dionne S, Seidman EG, Bitton A, Ward BJ (2007). Gut 56(6): 886-888.
  11. D’Souza Y, Eric Fombonne E, Ward BJ (2006). Pediatrics 118(4): 1664-1675.

Orthodoxy? – Revisiting the Cartwright Report (Part 2)

NZ Skeptic issues 96, 97 and 98 contained articles presenting different viewpoints on the ‘Unfortunate Experiment’ at National Women’s Hospital and its aftermath. Wellington registered nurse and NZ Skeptics treasurer Michelle Coffey continues the discussion in this web-only special.

When I wrote my original article (NZ Skeptic 97), it was written with the intention that it could stand alone as a more thorough discussion of the findings of the Cartwright Report and later research. This was because there were a number of important issues raised as a result of the report which have been almost lost in the debate, many of them systemic ones. While I’m sure that readers interested enough can source the relevant material and judge for themselves, in Skeptic 98, Linda Bryder has responded and the statements made merit a response to clarify several points. I referenced the Bryder’s book for a complete review of the topic, but did not address it in the original article as while it does deal with aspects of the ‘Unfortunate Experiment’ the book ultimately fails to provide any complete assessment of the matter due to the book omitting to investigate key figures such as McIndoe or dealing with the health care system (in particular it’s politics) as opposed to social movements.

1. “There was no medical certainty about the proportion of cases of CIS…”

None of the references support the contention that there was no medical certainty about the proportion of CIS cases that would advance to invasion, and in any case proportion of cases isn’t the point – it’s whether CIS was considered to be a precursor of invasive cancer. This appears to be the case. In the Cartwright Report1 (p23) a compilation of studies was introduced into evidence giving figures that indicate over time, a significant proportion would progress to invasion.

The 1976 Editorial2 cited is discussing screening and states “The report faces up to the problems which still cause fierce controversy – those of the natural progression and regression of early lesions, the discrepancy between total [CIS] cases and the combined number of number of clinical invasive cases, and the incidence and mortality rates.” The Walden Report3 it is referring to states unequivocally that “The significance of [CIS] as a precursor of invasive disease has been recognised for more than 3 decades. Several series of patients, followed for months or years, have demonstrated progression from [CIS] to invasive disease at rates ranging from 25 to 70%.” The issue of where earlier dysplastic changes fit appears to be where any “controversy” laid rather than the concept of progression from pre-invasive lesion to invasion. The report placed these earlier changes a decade or so prior to invasive disease as a precursor state stating “the concept that progressive degrees of cervical dysplasia are part of the natural history of neoplastic disease of the cervix now seems firm.” This is relevant to developing a screening programme given that there is a window of many years in which the condition could be detected and treated. Ostor4 in his statement “The ultimate fate of patients with CIN is the most controversial issue facing investigators interested in cervical neoplasia.” is discussing similar issues to that discussed in the Walden report which is relevant in terms of assessing the relevance of findings and being able to predict the behaviour of these ‘atypias’. Most studies ended at the point of CIS. Ostor looked at not only progression to invasion but the likelihood of regression, persistence and progression to CIN3 (11% in the case of CIN1) with the conclusion that the probability of invasion increases with severity of dysplasia, but there is potential for regression which reflects on therapy.

One man’s dysplasia is another man’s carcinoma #40;notably without insertions to influence the reader to place a particular meaning on it) is a statement that crops up frequently. One issue is the correlation between cytology and histological confirmation, while this wasn’t perfect it was generally agreed that smears could reliably indicate an existing lesion. Histological confirmation was required, but there could be a lack of agreement between pathologists and laboratories on the histological criteria meaning that the precise differentiation between dysplasia and CIS varied. These uncertainties don’t seem to have impacted on the confidence of pathologists regarding screening for cervical malignancies and grading of a lesion was seen by surgical pathologists as more a statement of probability of progression which had limited applicability in clinical management as noted in Löwy’s history5. The precise definition didn’t matter as much as understanding that it was the same disease that was being managed. This is nothing other than a fairly typical debate as biology and medicine rarely, if ever, give certainties.

1. ” Coffey cites 1958 ” official policy… to show this.”

It’s important to note for clarity that there could be variation in policies in other areas but what is more critical in this case was policy at NWH, the hospital where Green practised which set the standard of care. Policies at NWH evolved over a period of time. In 1955 the formation of a cancer team to which all cases of carcinoma of the cervix were to be referred to for treatment was unanimously supported. Over the next ten years, policies regarding the diagnosis and treatment of CIS and invasive cancer were regularly reviewed. This wasn’t just agreed to at a meeting of “…only nine senior consultants…”the decision was made a formal meeting of the Hospital Medical Committee, with a majority which indicates that the committee was happy with the level of evidence for the policy. The clear majority and evolving policy don’t seem to fit too well with the narrative that there was considerable medical uncertainty and controversy about CIS and its progression.

2. “Professor Barbara Heslop explained this more appropriately…”

Heslop’s6 article is one to which I referred to in writing my article as I found some aspects of it informative. However, it is based in the opinions of the author so it’s unsafe to use this article to make certain statements about Green. Heslop considers that Green was doing research but seeks to place this in context stating “Herb Green aimed to ‘prove’ his hypothesis by carefully observing that dysplasia did not lead to cancer…Unfortunately, the proposed methodology was equally appropriate for showing dysplasia did lead to cancer. Paradoxically, and I am sure unintentionally, he ended up demonstrating…more convincingly than had been done before, the transition of dysplasia to cancer.” It was demonstrable that Green considered his work as a study initiated to test a theory and his 1974 paper said (p65) “This…represents the nearest approach yet to the classical method of deciding such an issue as the change or not of a disease from one state to another – the randomised controlled trial. It has not been randomised and it is not well controlled but it has at least been prospective…”

While Baker may have had the presumption that the therapeutic relationship would predominate, little suggests this happening in the case of Green. Whether he knew about such things as falsifiability, Green set out to prove his ‘dormant cancer’ idea despite indications early on that following such patients was unsafe (such as three cases of invasive disease in patients followed with positive cytology occurring by 1969). If the therapeutic relationship was predominant, those cases should have prompted reconsideration of the hypothesis; instead they were reclassified and removed from the study.

3. The 1966 management protocol was to “extend” conservative treatment…”

What seems to be being said here is that under 35 doesn’t mean that, but that it means older patients can be included as well. It should mean what it says as this was a safeguard intended to protect patients which Green then breached. When aging occurs, physiological changes mean it is more difficult to view areas of abnormality and Green and his colleagues were aware of this and the additional risks. The report (p37) stated “As a woman gets older, the squamocolumnar junction is more likely to lie in the endocervical canal and therefore be invisible to the colposcopist.” This means that it can’t be determined whether lesions extending further are suspicious and it was impossible to get a sample without a cone biopsy. Older women were more likely to have unsuspected invasive carcinoma. The use of words like treat is misleading as the intention was not to extend conservative treatment, but to monitor women with positive cytology to fulfil the aim of the proposal. As an example the proposal stipulated punch biopsies and used the word treat and treated (p 21 “four have been treated by punch biopsy alone.”) however this was regarded as a diagnostic procedure. The only way a punch biopsy could be a ‘treatment’ is if somehow by accident or design, the biopsy managed to obliterate a small lesion.

4. “Coffey presents this as a negative outcome, as if it was unnecessary outcome for the women.”

It was. There is a difference between ongoing monitoring which often can be done at primary care level and repeated attendances at a hospital over many years for multiple tests and interventions. Patient 4M (p44) was first admitted in 1970 with abnormal smears. In between 1970 and 1983 she had 38 appointments and six biopsies (wedge, ring, cone, surface) were performed with two occasions being histologically incomplete. A review of patient notes (p42) showed many women had more than one cone biopsy and in some cases up to six. Testimony showed that doing this more than twice was not considered unless under exceptional circumstances and doing this procedure could have effects such as stenosis or haemorrhage and make later evaluation difficult. Bonham testified that this was a dangerous practice and with the third or fourth conisation, it was probably a greater risk than hysterectomy.

Nothing in medicine is benign, and there are obligations to treat patients ethically. This includes minimising as far as possible unnecessary medical procedures as there are a number of risks entailed every time intervention is made. In a condition as treatable as CIS that could have been simply excised that means that over a period of time many women had a number of procedures that were unnecessary and posed excess risk to them that still left them with positive cytology resulting in risk of progression with its own complications. The associated disruption, pain and discomfort of these multiple interventions shouldn’t be trivialised.

5. Regarding the infant vaginal swabs, a press release by Judge Cartwright’s counsel stated “Mothers were told of the tests.”

Any kind of consent would have sufficed. Judge Cartwright stated (p141) “&#8230 there was no provision made to comply with the fundamental requirement that children are not included in research with the consent of their guardians.” This was not a test but a trial and was non-therapeutic research that held no benefit for the infant. Green quickly realised after 200 babies had undergone the procedure that it was a waste of time and lost interest in the study without communicating this to the nursing staff leading to over 2000 babies being subjected to an unnecessary and potentially harmful vaginal vault smear for the purposes of research without the consent of their parent or guardian.

With randomisation of Green’s 1972 “R series” radiotherapy and hysterectomy trial it is difficult to see that it conformed to international practice. Randomisation is aimed at preventing systematic differences between groups and preventing bias but in this case, the selection criteria were made in advance but there was no allocation of patients prior to anaesthesia, grading and decision on surgical treatment so no concealment. Enrolment could have been influenced by biases such as the need to enrol sufficient patients into the study along with the potential for further bias to be added with the use of coin tossing. The patients were not given any opportunity to consent, and were mislead about the treatment decision. Testimony on p170 states “Dr Green and myself and others discussed this question of informing women in the trial about it when it was initiated in 1972. We decided in the end not to tell patients about the trial. We told them they would be examined under anaesthetic when the most appropriate mode of treatment would be decided and then we would proceed accordingly.”

I can contrast this lack of any kind of consent from the parents or “R series” patients with the oral consent obtained by Sir Liley for his intra-uterine infusions where he sufficiently informed the patient of the possible risks and that the treatment was experimental. His case study published in 19637 states “the patient and her husband were an intelligent couple, and the prognosis for the foetus, the possibility and uncertainty of intrauterine transfusion, and the potential hazards to the mother were fully explained to and discussed with them.” This was not the case with Green and his research projects, as no real attempt was made to provide any kind of informed consent.

6. “Despite writing this, Coffey herself makes it clear that the two groups…had nothing to do with the two groups whose records Green analysed.”

This is an assertion and no reason is given as to why you state this. As such, there is nothing there to counter other than to say they had everything to do with those groups. McIndoe et al8 was retrospective while Green’s research was prospective, which made a difference in how the study was conducted but they were measuring the same thing as Green’s 1974 paper (p65) describes: “This series of 750 cases of in situ cervical cancer, and the following of 96 of them with positive cytology for at least two years…” The McIndoe paper was also a comparison of two groups of women, one with normal follow-up cytology and one without and was the final paper that Green never wrote that completed follow-up on the patients that were the subjects of his study. In my discussion, I highlighted the summary in the paper of patients who were included in the punch biopsy special series and that alone should make it clear the relationship between the “special series” and the study. I’m sure if Green could have asserted the same he would have, but couldn’t. The report didn’t rest on this paper alone but reviewed 1200 patient files and 226 were used as exhibits.

7. “Cartwright accepted this as “accurately reflect[ing] the findings of the 1984 McIndoe paper.”

Except Judge Cartwright did not. This is selective quotation that distorts the statements in the report and falls short of what you would expect from an historian whom you would expect to take care to fairly represent the context and statements in documents. The statement is from Ch4 “Expressions of Concern” where the article is addressed as it was the subject of public comment and had prompted the Hospital Board to request an inquiry. This put the article under scrutiny and criticism by some witnesses. Under the title “Was the magazine article accurate?” It is stated that the manuscript was submitted and editorial changes explained but there were some errors in the article that was finally published. This section states:

1.Significant editorial changes: The matter of accuracy was raised firstly by the authors themselves. In her evidence Sandra Coney drew attention to two editing changes which she considered substantially altered the meaning of sentences in the magazine article.

a. “Twelve of the total number of women had died from invasive cancer as had four, or 0.5%, of the group-one women, and eight, or 6% of the group-two women who had limited or no treatment.”

In the original manuscript the authors had written: “Twelve of the total number of women died from invasive carcinoma. Four (0.5%) of the Group-one women, and eight (6%) of the Group-two women who had limited or no treatment. Thus women in the limited treatment group were twelve times more likely to die as the fully treated group.”

I accept that the unedited material more accurately reflects the findings of the 1984 McIndoe paper. The edited version is not accurate.

It’s clear when looked in context that the statement was sourced from the original manuscript of the article and those words cannot be attributed to Cartwright. Cartwright is accepting that the original manuscript more accurately reflected the findings of the paper and is being misquoted to say something else. It is of note that in Bryder9 p33 that this statement is used to say “Cartwright too suggested differential treatment. In her report she quoted Coney and Bunkle’s statement that: ‘Twelve of the total number of women died from invasive carcinoma… [etc]” Cartwright accepted that this accurately reflected the findings of the 1984 McIndoe paper.” This statement is again used misleading to say something other than what it actually says and is being used inconsistently.

8.“How had they “returned to negative cytology”

McIndoe did not say treatment did not enter the study. The citation in Bryder used to reference this says only “The detailed management of patients is not under consideration in this paper…” The paper looks at the initial management and in some cases more detailed management of patients as Bryder would be aware. Here, it does become evident that there were differences, for instance in group 1 cone biopsies excision was incomplete in 24%, but in group 2, 74% were incomplete with the difference likely to be largely due to management where complete excision is not a necessity. The paper states “…any examination of the natural history of CIS of the cervix must depend on a representative, though incomplete, biopsy specimen on which to base the initial diagnosis. Thereafter, meticulous long-term follow-up of all patients using techniques such as clinical examination, cytology, and colposcopy, and if indicated biopsy, is required.” The paper detailed some limitations, such as small biopsies or possibly trauma eradicating lesions, or inadequate biopsies missing abnormalities. So in answer to that question, it was because initial management in group 1 patients either intentionally or unintentionally was adequate in treating the lesion and restoring them to negative cytology. Of this group only 0.7% had recurrence of CIS. In group 2, follow-up showed continuing positive cytology after initial management either by limited biopsy or incomplete treatment which was ideal for studying the natural history of CIS as set out in the 1966 proposal.

9. “Coffey refers to the 1986 paper…as critical of conservative treatment…”

This paper10 was only briefly mentioned before moving on with discussion of McIndoe et al as there was insufficient space to deal with it in detail. Here long term follow-up of vulvar carcinoma shows that of 31 patients managed by surgical excision, there were 4 recurrences and one developed a vulvar carcinoma 17 years later. 4 women managed only by biopsy progressed to invasion in 2-8 years and one additional patient managed with incomplete excision after a lengthy period of observation progressed to invasion. The paper demonstrated that untreated lesions have significant invasive potential. This approach was an extension of Green’s study of CIS of the cervix, and in this case a biopsy cannot be considered treatment at all. While the authors were advocating conservative treatment this was excision of the lesion not biopsies or incomplete excision.

10.“Would a modern gynaecologist agree with this assessment?”

The relevant sentence is presented as a statement, but it omits a significant portion of the sentence which is “This needs to be explained, as those figures strongly suggest the progression of CIS to invasion when it is and was a totally curable lesion.” Gynaecologists would accept the statement that CIS is a curable lesion which can be readily treated with a variety of local destructive methods with complete removal of the lesion and reversion to negative cytology which then prevents the risk of the lesion progressing. In the quoted statement McIndoe et al is referring to group 1 patients, whose cytology had returned to normal. It states “However, contrary to what would be expected, of the 139 group 1 patients with incomplete excision of the original lesion, only five (3.5%) later developed invasive carcinoma. Thus whether or not the lesion is completely excised does not appear to influence the possibility of invasion occurring subsequently.” In this case it didn’t, the rate of recurrence was unexpectedly small probably due to the initial intervention influencing the condition.

Treatment of a diagnosed lesion is then conflated with cervical cancer at a population level in asking for an explanation of why cervical cancer hasn’t been completely eliminated. In an ideal world this might be possible, but in the real world there are a number of difficulties to be faced in ensuring the entire population at risk is screened and treated if necessary. Green’s conclusion was that screening was not effective, however the conclusion was unjustified. The report discusses this on page 56 and crucially treatment needs to improve the prognosis as if subsequent cases are not adequately treated there is little value in screening in the first place. Also, if screening is done in low risk cases and high risk populations are missed, that means screening will be limited in being able to affect morbidity and mortality. In McIndoe et al, the age-standardised incidence of invasive carcinoma in group 2 was 1141/100,000 compared with 18.2/100,000 in the general population in 1975. This has since dropped considerably.

11. “As stated above, group 1 and group 2 had a similar range of treatments…”

My statements stand on this matter that “this ignores that while many women were treated with various procedures, there was evidence of continuing disease, demonstrating that the intervention was inadequate. This was not followed up, posing a high risk of development of invasive disease.” To prove that CIS is not a premalignant disease necessitated the area is sampled for diagnosis, but done in a way that left the lesion available for further study. In some cases there was no treatment, for instance the punch biopsy series which only used a diagnostic method. The criteria included that “the colpscopically-significant area is large enough not to be completely excised by the diagnostic punch biopsy.” The intention was to leave the lesion as undisturbed as possible. The use of cone biopsy is covered in q 5 and 9 as this could also be diagnostic. Of the hysterectomy series, only 4 out of 25 had the procedure for CIS so the procedure was done but not often specifically for CIS. Either way, women were left with positive cytology which put them at risk.

12. ” The methodology of the 2008 paper has been questioned by Sandercock and Burls…”

I would be embarrassed to cite this letter11 as an example of “questioning”. Every paper is flawed to a degree but this isn’t the right criticism to make. They cite a secondary source and claim this explains what they say is a problem with McIndoe et al – “He points out that, not only were the two group retrospectively divided on the basis of persistent abnormal cytology during follow-up and not prospectively as experimental groups for the comparison of different treatment strategies…” They misread the letter12 which does not appear to state anything regarding type of study and apparently draw from Overton’s misleading statement that “…Green and other senior NWH clinicians endorsed policy changes in dysplasia management. Younger women were to be continuously monitored, by repeat smears, colposcopy, lesser biopsies and appropriate more major surgery if evidence of early cancer.” which omits mention of Green’s role and his published studies. Sandercock and Burls then make an erroneous conclusion that McIndoe’s research should have been prospective and be following different treatments without realising that prospective research had already been done by Green. They cannot have read McIndoe et al despite citing the paper otherwise they would have seen the paper outlined the 1966 proposal. A few minutes reading would have shown the difference in between the statements which if they were honestly critiquing the study they should have checked.

Sandercock and Burls then claim a similar “problem” with McCredie et al even though they are aware it was retrospective. This might be correct to say for prospective studies that ask a question and look forward such as Green’s as this type of study should assess outcomes relative to interventions but retrospective studies are meant to pose a question and then look back. McIndoe et al looked at the question of outcomes for patients with CIS with the patient groups defined by presence of positive or negative cytology which categorised according to the risk they had persistent disease. McCredie13 takes this a step further with the approach being to look at the question of outcomes for patient groups classified by management that was adequate or inadequate. There is no problem with this approach; the problem lies with Sandercock and Burls.

13. “…It should be noted a study on outcomes cannot make such pronouncements…”

It can however tell a story, one that is further strengthened by understanding what the author is trying to achieve. Papers are meant to be considered in the light of all the evidence and that includes context. McCredie et al shows half the cancers in women initially managed with punch/wedge biopsy were diagnosed within 5 years of a finding of CIN3. It can be judged objectively there that merely doing a diagnostic procedure in patients with CIN3 leads to a high risk of developing cancer in a relatively short period of time, while the context shows up much more and shows the unethical nature of the original research which meant they were managed in that manner.

14. “Yet Green’s achievement was to encourage an openness to look at the evidence.”

Which story is it that is being referred to? The one where there is a controversy in medicine? If so, he wasn’t the spirited free-thinker he is being cast as. If it is the one where Green was the controversial one, willing to question modern medicine then the controversy wasn’t in medicine. If he is going to be cast as Galileo type of figure, persecuted for his heresy, the critical point is that Galileo was proven correct. So where are his papers? Even his supporters never present his papers to support their claims. Their resort is to complain about everything else.

Green’s ‘achievement’ was the reverse. On p108 of the report, in an Auckland Star article in 1972 it was reported that “Professor Green asserted that a woman with a positive cervical smear showing what is called [CIS] is no more likely to develop invasive or malignant cancer of the cervix than any other woman of the same age. In other words, in situ cancer is not a forerunner of invasive cancer, and the smear test is over-rated.” There is no shift in attitude over time, despite that over the years, much more would have been studied on the matter and medical practice would have changed. Green’s set views were taught, leading to Registrars and other staff being under the impression that screening for cancer precursors was a waste of time. Apparently he kept an Ogden Nash quotation on his blackboard for many years saying “My mind is made up – don’t confuse me with the facts”. None of this shows any willingness to debate the evidence; on the contrary when faced with evidence of patients with invasive cancer that he had originally diagnosed with CIS though not a trained pathologist, he reclassified them and excluded them from the study. They did not fit, so he changed the evidence to suit his theory. True scepticism is not about holding an idea or defending a position but about being open to the evidence and being willing to examine it and change if necessary. Hitting on the hard edges of scientific debate is a tough experience but it serves no one if the record is distorted to hold an untenable position and legitimate questioning of this is taken to be persecution instead of honestly examining whether the position is, in fact, a correct one to hold.

References

  1. “The Cartwright Report”: http://www.nsu.govt.nz/current-nsu-programmes/3233.asp
  2. “Screening for cervical cancer” 1976: BMJ 659-60
  3. The Walden Report: June 5, 1976: CMA Journal Vol. 114 1003-1012
  4. Ostor, AG 1993: Intern. J. Gyn. Path. 12, 2, 186-92
  5. Lowy, I July 2010 Historia, Ciencias, Saude – Manguinhos V. 17, supl. 1, 53-67
  6. Heslop, B 2004: NZMJ 117,1199
  7. Liley, A.W. 2 November 1963: BMJ Vol 2, Issue 5365 1107-1108
  8. McIndoe, WA; McLean, MR; Jones, RW; Mullins, PR 1984: Obstet Gynecol. 64, 4, 454.
  9. Bryder, L 2009: A history of the ‘Unfortunate Experiment’ at National Women’s Hospital, Auckland University Press, Auckland
  10. Jones, RW; McLean, MR; 1986: Obstet Gynecol. 68, 4, 499-503.
  11. Sandercock, J. Burls, A. 2010, NZMJ 123, 1320
  12. Overton, G.H. 2010, NZMJ 123, 1319
  13. McCredie, M. 2010, NZMJ 123, 1321

The Unfortunate Experiment: Revisiting the Cartwright Report

This article is a response to ‘Truth is the daughter of time, and not of authority’: Aspects of the Cartwright Affair by Martin Wallace, NZ Skeptic 96.

The Cartwright Inquiry1 was held after the publication of “An Unfortunate Experiment at National Women’s” in Metro magazine in June 1987. The events leading up to the publication of the article and the findings of the subsequent inquiry have been contested ever since.

The inquiry heard from 67 witnesses, many doctors, 84 patients and relatives, and four nurses. In addition, 1200 patient records were reviewed, with 226 used as exhibits. The final report released in August 1988 has had a long-lasting impact. It recommended many changes in the practice of medicine and research, including measures designed to protect patients’ rights and a national cervical screening programme. These have since been implemented. The Medical Council announced in 1990 that four doctors were to face disciplinary charges resulting from the inquiry’s findings of disgraceful conduct and conduct unbecoming a medical practitioner. Charges against Dr Herbert Green were dropped due to ill health.

The report of the Committee of Inquiry has withstood many challenges, including judicial reviews and many articles alleging its findings to be flawed. Yet there have been allegations of a miscarriage of justice, charges of a witch-hunt, even a feminist conspiracy.

Where does this leave Dr McIndoe and others who had mounting concerns for so many years? Why did so many women develop cancer? In this article I will explore the findings of the Cartwright Inquiry, its context, the research and the criticisms, and attempt to find a more nuanced understanding of the “unfortunate experiment” and its ongoing effects. Page numbers in parentheses refer to pages in the Cartwright Report. CIN3 and CIS are interchangeable terms for a lesion of the cervical epithelium which can be a precursor to invasive cancer.

The Findings of the Inquiry

The report found that Green, rather than developing a hypothesis, aimed to prove a point (p 21) that even at the time was known not to be the case. A 1961 compilation of studies from Paris, Copenhagen, Stockholm, Warsaw, and New York showed CIS progressed to invasive cancer in 28.3 percent of cases (p 23). As at 1958 the official policy was “… treatment of carcinoma of the cervix Stage 0, [CIS] should be adequate cone biopsy … provided the immediate follow-up is negative and … the pathologist is satisfied that the cone biopsy has included all the carcinomatous tissue” (p 26). Standard treatment of the time involved excising all affected tissue and the ‘conservative’ treatment of conisation was in use well prior to 1966.

Green’s initial proposal stated “… It is considered that the time has come to diagnose and treat by lesser procedures than hitherto, a selected group of patients with positive (A3-A5) smears. Including the four 1965 cases, there are at present under clinical, colposcopic, and cytological observation, 8 patients who have not had a cone or ring biopsy. All of these continue to have positive smears in which there is no clinical or colposcopic evidence of invasive cancer”… The minutes then record that “… Professor Green said his aim was to attempt to prove that carcinoma-in-situ (CIS) is not a premalignant disease”… (p 22). This appeared to come about because of concern about unnecessarily extensive surgery for CIS between 1949 and 1962. During this period, some centres were beginning to use cone biopsy as effective treatment; however there were limitations to its use (p 27).

There were some questions over whether the work was a research project. The inquiry concluded this was the case and that a research protocol, however flawed, was put in place (p 69). Green published in peer-reviewed journals on his hypothesis and findings. By 1969, three cases of invasive disease had occurred in patients with positive cytology monitored for more than a year, and this should have made it clear that following patients with persistent CIS was unsafe (p 52).

Green then explained those patients by concluding that they’d had invasive cancer that was missed at the outset. The report contends this was dangerous to the patients as it demonstrated that the proposal was incapable of testing the hypothesis. These patients were reclassified by Green and the patients removed from the study (p 55). In addition, patients over the age of 35 were included in the research in breach of the protocol vp 49).

There were many subsequent issues, including lack of patient consent (p 136). Patients also had to return for repeated tests and other invasive procedures, often receiving general anaesthetics in the process (p 42-49). A collection of cervices from foetuses and stillborn infants and another of baby uteri in wax were collected by Green for research which was later abandoned. This did not appear to comply with the Human Tissue Act (1964) as no consent was obtained from the parents of the stillborn infants (p 141).

As part of an earlier 1963 trial to test whether abnormal cytology in women later developing CIS or invasive cancer was present at birth (pp 34 & 140), 2,244 new-born babies had their vaginas swabbed without formal consent from the parents (there was a decision to abandon this trial soon after it started but this wasn’t communicated to nursing staff until 1966).

Procedures such as vaginal examinations and IUD insertions/removals on hysterectomy cases were performed by students without patient knowledge or consent while they were under anaesthetic (p 172). There was a further study on carcinoma of the cervix treatment, where patients either had radiotherapy alone or hysterectomy and radiation (p 170). The method of randomisation was by coin toss.

The Research

The idea that patients were divided into two experimental groups arose from McIndoe et al (1984)2. The patients were divided retrospectively into two groups which overlapped strongly but not completely with groups defined by Green, that he called “special series”. In his 1969 paper, cited in the report (p 40-41) he stated: “The only way to settle the question as to what happens to carcinoma in situ is to follow adequately diagnosed but untreated lesions indefinitely … it is being attempted at NWH by means of 2 series of cases. (I) A group of 27 women … are being followed, without ‘treatment’, by clinical, colposcopic, and cytologic examination after initial histological diagnosis of carcinoma in situ … has been established by punch biopsy … (II) A group of 25 women who have had a hysterectomy (4 for cervical carcinoma in situ) and who now have histologically-proven vaginal carcinoma in situ, has been accumulated …” This was done semi-randomly, with cases presenting themselves fortuitously.

The outcome for the group of 25 who were included in the punch biopsy “special series” was summarised in the McIndoe et al (1984) paper. Nine out of 10 women who were monitored with continuing positive smears developed invasive cancer. Only one out of 15 women who had normal follow-up cytology later developed invasive cancer. While Coney and Bunkle may have made a mistake, it’s clear the judge didn’t. The report states: “Green’s 1966 proposal was not a randomised control trial, but it was experimental research combined with patient care” (p 63).

Green’s interpretation of the data in his 1974 paper is suspect, having concluded that the progression rate was 7-10/750 (0.9 to 1.3 percent) or 6/96 (6.3 percent) of ‘incompletely treated’ lesions (p 54). These were explained by suggesting that either invasive cancer was missed at the start, or over-diagnosed at the end. Dr Jordan (expert witness) deemed this interpretation incorrect as of the 750 cases, 96 had continuing positive cytology, meaning that the other 654 patients could be considered free of disease. Of that 96, 52 patients had not been assessed further, making it impossible to know whether or not this group already had unsuspected invasion. Of the 44 patients remaining with ongoing carcinoma in situ who had more investigations, seven were found with invasive carcinoma. The incidence of known progression was therefore 7/44 (16 percent), which approximates McIndoe et al (1984) findings. This means that the proportion of invasive cancer cases in those inadequately treated was much higher compared with those who had returned to negative cytology, even before any cases where slides were re-read and excluded are considered.

McIndoe et al (1984) covered the follow-up data for 948 patients with a histological diagnosis of CIS patients who had been followed for a minimum of five years; there was a further paper in 1986 regarding CIS of the vulva. The same method used by Dr Green to group women by cytology after diagnosis and treatment was used, but using the correct denominators and the original diagnosis. Patients who were diagnosed with invasive cancer within one year were excluded to avoid the possibility the cancer had been missed initially. The management was cone biopsy or amputation of the cervix in 673 patients, with 250 managed by hysterectomy. The only biopsies in 25 women were punch biopsy (11), wedge preceded by punch biopsy (7) and wedge biopsy alone (7). Twelve out of 817 (1.5 percent) of group 1 patients developed invasive cancer. Given the lengthy follow-up with negative cytology for group 1 patients, the authors concluded these represented the development of new carcinoma. There were marked differences in the completeness of excision between the two groups and the second group shows markedly different results, with 29/131 (22 percent or 24.8-fold higher chance) with positive cytology developing invasive cancer. At 10 years this was 18 percent rising to 36 percent after 20 years, irrespective of the initial management or histologic completeness of excision. This needs to be explained, as those figures strongly suggest the progression of CIS to invasion when it is and was a totally curable lesion. The answer is that a prospective investigation, as done by Green, has to establish that invasive disease is not present, while conserving affected tissue that is required for later study. The argument has been posed that women in the second group did get cone biopsies and hysterectomies. This ignores the fact that while many women were treated with various procedures, there was evidence of continuing disease, demonstrating that the intervention was inadequate. This was not followed up, posing a high risk of development of invasive disease.

This differs from group 1 patients, who were successfully treated at the outset. It’s pertinent to point out that the Cartwright Report did not rely on this study (or the Metro article) to reach its conclusions, but on review of patient records.

There have been two follow-up studies. McCredie et al (2008)3 examined medical records, cytology and histopathology for all women diagnosed with CIN3 between 1955 and 1976, whose treatment was reviewed by judicial inquiry. This paper gave a direct estimate of the rate of progression from CIN3 to invasive cancer. For 143 women that were managed by only punch or wedge biopsy the cumulative incidence was 31.3 percent at 30 years and 50.3 percent in a subgroup who had persistent disease at 24 months.

The cancer risk for 593 women who received adequate treatment and who were treated conventionally for recurrent disease was 0.7 percent at 30 years. These findings support McIndoe et al (1984) and extend the period of follow-up.

McCredie et al (2010)4, described the management and outcomes for women during the period 1965-74 and makes comparisons with women diagnosed 1955-64 and 1975-76. This showed that women diagnosed with CIN3 in 1965-74 were less likely to have treatment with curative intent (51 percent vs 95 percent and 85 percent), had more follow-up biopsies, were more likely to have positive cytology during follow-up and positive smears that were not followed by curative treatment within six months, as well as a higher risk of cancer of the cervix or vaginal vault.

Those women initially managed by punch or wedge biopsy alone in the period 1965-74 had a cancer risk 10 times higher that women treated with intention to cure. This was despite the 1955-64 group being largely unscreened, which would have delayed diagnosis. This study is important as it shows the medical experience of the women, where they were subjected to many interventions that were not meant to treat but rather to monitor.

Whistle blowing

Scientific misconduct happens, and for those trying to address it the risks are high. Brian Martin5 looked at several cases, and stated: “In each case it was hard to mobilize institutions to take action against prestigious figures. Formal procedures, even when invoked, were slow and often indecisive.”

McIndoe and others encountered similar difficulties and ultimately failed to get Green’s proposal reviewed. The concept of “clinical freedom” (p 127), where the doctor was the arbiter of the best course of action for the patient, was one major issue to emerge from the report. Colleagues tended to be very reluctant to intrude upon this, and this meant that the proposal could continue with little oversight or intervention. McIndoe had mounting concerns, particularly after 1969, which were disregarded or treated lightly.

These concerns were shared by pathologist-in-charge Dr McLean, and were raised internally with Medical Superintendent Dr Warren, who consulted with the Superintendent-in-Chief, Dr Moody and an internal working party set up to look at the issue in 1975. Twenty-nine cases that had developed invasive disease were referred to it; however only 13 were examined, and having set up its own terms of reference it only considered whether the protocol had been adhered to and disregarded concerns about patient safety (p 83).

The 1966 proposal effectively ceased when McIndoe withdrew colposcopic services and Green reverted to cone biopsy in most new cases (p 88), but it was never formally terminated. While Green himself did not take any steps to prevent the review of records by McIndoe and colleagues, Bonham did, and wrote a letter to the Medical Superintendent (p 92).

There are some important lessons to be learned from this, including that those with the authority to deal with the situation should make the best effort to achieve a balanced view of the situation and assess it fairly to allow the claimant a fair hearing.

Conclusions

The potential risks of Green’s proposal outweighed any benefits such as avoiding hysterectomy or cone biopsy. Invasive cancer could not be ruled out because there were poor safeguards against the risk of progression. This was unethical from the outset, regardless of the issue of informed consent. In addition, patients that developed invasive disease had their slides reclassified and were removed by Dr Green from the study. This would be considered research misconduct then and now as it manipulated the data.

It does not matter if the initial motivations were sincere; they ultimately fail on these points. This proposal had a very human cost. Moreover Green’s views had long-term effects, including influence on undergraduate and postgraduate medical students, and support for the attitude that cervical screening was not worthwhile. This ‘atypical’ viewpoint was also promoted in the scientific literature and in the press, creating confusion within the medical scene and with the public.

It can be incredibly hard to admit our failings and let go of old loyalties. In the aftermath of the report many doctors objected to cervical screening, ‘unworkable’ consent forms and the intrusion of lay committees on practice6. It’s true this had negative effects on the perception of doctors overall, particularly in regard to practices that were widespread in hospitals at the time, and there were times that unfair criticisms were aired. This impacted on the nursing profession as well, for nurses are meant to be patient advocates.

This was also about power. The really unfortunate thing is that medical responsibilities to patients are almost totally ignored in the midst of the argument, when they should be brought to the forefront. Likewise respect, justice and beneficence were lacking for the patients involved. No doctor raised concerns about the lack of consent, even though from the 1950s there was the growing expectation that this be sought, particularly with participants in research.

The Medical Association working party that examined this stated that it was “regrettable that the trial deteriorated scientifically and ethically and did not change as scientific knowledge advanced or as adverse results were observed”7. They found it deplorable that patients involved did not know they were part of a trial, and that it took a magazine article for it to be investigated.

Unfortunately, instead of addressing this and examining whether Dr Green made any errors or misinterpretations himself, the findings in McIndoe et al (1984) and other papers were not accepted. There is the unfortunate implication that, rather than there being mounting and valid concerns over decades, that Green was unfairly toppled and the resulting inquiry was a whitewash.

The report couldn’t have been written without the assistance of the medical community as expert witnesses and advisors. It’s not surprising that there would be loyalty for a colleague, but perhaps instead of attempting to rehabilitate Green it’s time McIndoe and his colleagues were vindicated. Morality did not totally fail and attempts were made to prevent patients being harmed8.

Acknowledgements: many thanks to Dr. Margaret McCredie of Otago University who assisted me with my research.

  1. The Cartwright Report: www.nsu.govt.nz/current-nsu-programmes/3233.asp
  2. W.A. Mcindoe; M.R. McLean; R.W. Jones; P.R. Mullins 1984: J. Am. Coll. Obst. 64(4).
  3. M.R.E. McCredie; K.J. Sharples; C. Paul; J. Baranyai; G. Medley; R.W. Jones; D.C. Skegg 2008: The Lancet Oncology DOI:10.1016/S1470-2045(08)70103-7
  4. M.R.E. McCredie; C. Paul; K.J. Sharples; J. Baranyai; G. Medley; D.C. Skegg; R.W. Jones 2010: A&NZ J. Obst. Gyn. DOI:10.1111/j.1479-828X.2010.01170.x
  5. B. Martin 1989: Thought and Action 5(2), 95-102.
  6. J. Manning (Ed.) 2009: The Cartwright Papers: Essays on the Cervical Cancer Inquiry 1987-88. Bridget Williams Books Ltd.
  7. L. Bryder 2009: A History of the “Unfortunate Experiment” at National Women’s Hospital. Auckland University Press.
  8. C. Paul 2000: BMJ 320, 499-503.

University funds Therapeutic Touch

Why is Canterbury University fostering an alternative therapy at its Health Centre?

Should Canterbury University be funding pseudo-science? It was implied that this was occurring in a recent university press release:

Staff development awards of up to $5000 are available every six months for general staff. They are designed to recognise and assist professional development activities… One of the recipients this year is Wendy Risdon, who works at the UC Health Centre as a practice nurse. She will use her award to fund a trip to the US, where she will attend the 12th Annual Healing Touch International Conference in Milwaukee.

According to the Healing Touch International, Inc. website:

Healing Touch works with your energy field to support your natural ability to heal. It is safe for all ages and works in harmony with standard medical care.

When people start talking about someone’s energy field, especially with respect to medical treatments, alarm bells should start going off in your head. A simple Wikipedia search reveals several critical evaluations of the therapeutic touch practice.

In the press release, Wendy goes on to say: “I will be going to facilities that use complementary therapies such as Healing Touch as part of their mainstream care… Healing Touch is not particularly well-known or used here in New Zealand but I think there is a big role for it. My goal is to incorporate complementary therapies into mainstream medicine.”

It wasn’t clear what was happening down at the Health Centre, so I went to find out for myself. Wendy Risdon is a Registered Nurse at the UC Health Centre and a Level 5 Healing Touch practitioner. She was more than happy to talk about her work.

DM: How does Touch Healing work?

WR: It”s a biofield therapy, that means it”s utilising the magnetic fields of the body of both the person and the practitioner. And it”s helping to move energy around the body. And I guess people are more familiar with things like acupuncture when you talk about moving energy. It involves the energy centres of the body called chakras.

DM: Have you ever considered that the simple act of massaging could act as a placebo effect and that there are no auras involved?

WR: To a certain extent I do think that the simple interaction between two people in a caring environment has positive benefits. There are measurements which have been done on practitioners and the actual frequency or the Hertz of the vibrations that they”re sending out and so we know that different organs of the body vibrate at different frequencies. What I think happens is that the practitioner can influence those frequencies by the energy that they”re sending out.

Looking through the literature suggested by Wendy revealed many complicated scientific terms used in an attempt to explain the mechanisms behind Healing Touch. Terms borrowed from quantum physics, or just the word quantum were used with audacious frequency. To a person who has studied advanced quantum mechanics, it is clear that the words were being misused. This is known as argument by poetic language; the ‘if it sounds good, it must be right’ argument. Unless you’re a scientist, these things are sometimes hard to detect, but the measurements claimed to have been carried out on the auras are obviously junk science.

So who chooses the recipients of these awards? A panel of senior staff from the Human Relations department determines the best applicants and then makes a recommendation to the Vice-chancellor, Roy Sharp, who has the final say. He was ill in this case, so the final decision became that of Paul O’Flaherty, the Director of Human Resources.

DM: Do you know what Healing Touch is and did you do any research into Healing Touch?

PO: In the application, the application was supported by all the general practitioners at the Health Centre and the director of the Health Centre. One of the panelists rang the director and said, “We understand this is an alternative therapy. Just wanted to check that you did in fact support the application.” When they confirmed they did, we worked it on that basis.

DM: Do you believe the university should fund pseudoscience?

PO: I wouldn’t describe it as that. I took the view with this that this was endorsed by mainstream professional health practitioners.

It doesn’t seem like Human Resources are at fault here. They consulted with the on-campus experts in medicine. It also turns out that there were only three applications for the General Staff development awards this year and all three applications were successful.

Dr Joan Allardyce is the Medical Director of the UC Health Centre.

DM: When you first heard about Healing Touch were you at all sceptical and what research did you do regarding Healing Touch?

JA: I was interested to know how it would be applied and what benefits would be derived. Wendy gave a presentation to all the doctors and nurses and all the doctors and nurses were all happy about it. So basically what it is, is massage. She’s applied it when people have severe neck pains or migraines or really stressed. People go away feeling really improved.

DM: If Healing Touch is acceptable in your health centre, can other members of staff also use other alternative medicines such as homeopathy and magnetic therapy?

JA: No, they are not acceptable. I cannot believe in iridology. We’re not going in that direction. We are absolutely not going down the track of opening our doors to any crackpot out there. Definitely not.

DM: The Healing Touch practitioners, including Wendy believe the healing mechanism is manipulation of an aura. As far as you’re aware, does Health Touch vary from normal massage?

JA: Who knows, it probably doesn’t actually matter. It’s the outcome that matters.

And, of course, Joan is right. Massage Therapy is a well established treatment with peer-reviewed research to back up the results. However, when you rename Massage Therapy as ‘Healing Touch’ and try to explain it with auras and the transfer of energy it becomes pseudoscientific. Massage itself should be sold as such; there’s no need to use mystery and make-believe to help relieve someone’s physical manifestations of stress by giving them a massage, especially intelligent young university students who surely are trying to seek truth in their academic pursuits.

If alternative medicines worked beyond a placebo effect then they wouldn’t be alternative anymore, they’d just be medicine. Alternative medicines become dangerous when they are used in place of conventional medicine to treat more serious conditions. Treating a headache/stress or other psychological ailment is different from treating physiological conditions such as infections or cancer. People believe they’re getting a treatment that works, but they’re paying for something that is ineffective. And in many cases they”re not only paying for the treatment with money, but with their lives. There are many examples listed on the website whatstheharm.net In this case, it seems very unlikely that anyone will be harmed by the practice of Healing Touch at the UC Health Centre. All the medical staff are extremely competent. Healing Touch might work for you. But it has nothing to do with manipulating an aura around your body.

Why do some good doctors become bad doctors?

In NZ Skeptic 82, John Welch wrote that there was something about general practice which attracts an interest in complementary and alternative medicine (CAM). Is it acceptable for medical graduates with a science degree to be allowed to carry on in this manner? Should we amend the medical registration so they can’t? Is legislation needed to alter the culture-of doctors and society generally? This article is based on a presentation to the 2007 NZ Skeptics Conference.

Society confers upon the medical profession certain privileges, as it does upon lawyers, clerics, JPs and those entitled to issue warrant of fitness certificates. For the past 150 years or so the privileges enjoyed by doctors and those practising within the so-called orthodox health professions, have been granted and maintained upon the assumption that they undergo rigorous scientifically based education and maintain a scientific basis for their entire careers. The privileges can be quite rewarding in monetary and other terms.

We agree that the scope of such rewards implies an added burden of responsibility in understanding the nature of science and the requirements for application of scientific principles to clinical medicine. In modern society that is not as easy as it sounds. What follows is not a defence for doctors who may be failing to meet the assumed standards but rather our perceptions of why, so often, we doctors do as we do. We examine what we perceive to be a subculture which has always been present, but which may now be something of an epiculture.

For several thousand years doctors under various guises functioned independently of governments but not independently of the ruling classes. Various forms of Robin Hood-style financing kept the system going. Science, which essentially disproves current dogma progressively, infiltrated the healing arts. Medical education at university level in its present form dates back about 150 years. Paradoxically, junior doctors at Auckland City Hospital function much the way their forebears did at the Edinburgh Royal Infirmary 150 years ago. Old-style apprenticeships still guide aspirants to the various specialties and subspecialties within medicine. In most of the western world, consultants split their time between private practice, which they regard as a no-go area for government, and their hospital duties which enable them to keep up to date with new ideas and with young people. Conversely, most full-time hospital doctors are employees of the government.

This pattern had its beginnings in the 1790s. The industrial revolution brought social and demographic changes which had catastrophic effects on the health of the community. The politicians, perforce, had to react. Thus began the moves towards what we can loosely term socialised medicine. Third parties came into the doctor-patient relationship.

A crucial event occurred in 1938. Sensing the advance of socialised medicine ideas in Europe, the all-powerful surgeons of the American Medical Association sent a delegation to Europe which met with the surgeons of Nazi Germany, France and England. It was agreed that big insurance agencies, largely owned and controlled by the medical profession but attracting private finance, should be established immediately. The important corollary was that remuneration for the doctors would be on a procedural basis.

Patients would pay for a particular procedural process and not for the time spent in performing it. Such remains the basis for private practice throughout the western world and for much general practice. It is a crucial controlling factor on the way doctors practise and a powerful formative influence on the aspirations of young entrants to the profession. The net effect is that the bigger economic rewards occur outside and separately from the government. Possession of a particular technique, plus some entrepreneurial flair, is good for business.

There will always be some imbalance and mismatch of information between patients and their practitioners. So-called third parties have tried to intervene between patient and practitioner to modify the system. These third party ploys have largely failed, spectacularly in the case of US medicine. In what other industry would a cataract operation of brief duration secure a fee greater than that for key-hole surgery for gallbladder removal involving a much longer duration?

Over the last 50 years medical technology and basic medical science have advanced at the expected accelerating growth rates. What is not so obvious is the devastating effect this has had on general medical practice. A very powerful health-disease oriented industry now operates within the western world. The financial success of the doctors generally has been studied carefully by non-medically qualified people and a parallel or alternative medicine system has mushroomed. Its power is quite obvious in New Zealand when it is faced with threatening legislation based on calls for proven efficacy. The scientific concepts that knowledge is continually changing and must be continually reassessed, and that efficacy should be the basis for change of therapy and professional remuneration, play little part in the world of complementary and alternative medicine (CAM).

Checking a myth

About ten years after the first graduates emerged from the Auckland Medical School there was a widespread myth that Auckland students, having had more behavioural medicine in their undergraduate course, were much better at taking histories from, and establishing empathy with, patients. Conversely, Otago students were alleged to be much better at practical procedures.

One of us (JS) didn’t believe this and received a grant to compare the performance at hospital level of graduates from the two schools. The pervasiveness of the myth was fully confirmed by the consultants, matrons and hospital superintendents who still existed at the time, and by many of the former students themselves. However, I did not restrict my study to gaining the opinions of administrators, chief doctors and chief nurses. I went to telephone operators, the women in charge of the residences, laundries, kitchen staff, orderlies and charge nurses on the wards. I knew many of the Auckland graduates on an individual basis pretty well. What pained me deeply was learning that bright young people, both men and women, whom I had known fairly well as undergraduates and whom I regarded as sensitive, intelligent and obviously well fitted for medicine, had turned into arrogant, sometimes rude, aggressive, insensitive, awkward creatures who often were destructively disruptive of team functioning. Conversely, many of that group were highly successful in terms of acquisition of postgraduate diplomas and remunerated positions. I felt my own judgment had been severely challenged in terms of my starting opinion of these emerging graduates. I went back to Auckland with my tail between my legs but decided to analyse the situation further, knowing also that the myth was a myth.

Emerging pattern

A clear pattern emerged between the aberrant behaviour as I saw it of these young people and their attachments to clinical teams in the fifth and sixth years of their training. This clear-cut relationship involved role modelling, inspired somewhat by the personality of the emerging graduates themselves. More importantly, role models of the aberrant group demonstrating what I thought was unsatisfactory behaviour, had been adopted particularly from some surgical specialty teams led by powerful personalities who demonstrated essentially egotistical, flamboyant and at times outrageous behaviour, which was accompanied by affluence and considerable medico-political power.

Within North America and the British Commonwealth, and to a large extent in Europe, based on the leadership of a few doctors, patterns of medical profession behaviour have survived by resisting waves of political pressure from sociologists, politicians and economists. The great medical registration Acts of mid-nineteenth century Great Britain, are touted as wonderful examples of the altruism of the medical profession. But the transcripts of the Westminster proceedings and the antics of the medical profession at that time, particularly those of some prominent surgeons, reveal how the medical profession adroitly preserved its position. Conversely, the divide between general practitioners and emerging specialists was ensured. Nevertheless, a great deal was gained for the population generally, in terms of paving the way for more scientific application to the practice of medicine. In 1945, with the introduction of the NHS, the specialists or consultants in Great Britain again feathered their nest at a time when the whole framework of state-supported practice was changed. In the late 1990s matters came to a head when for the first time a general practitioner was made Chair of the Greater Medical Council of Westminster. Things have changed since then but, in our opinion, the essential reform steps have yet to be undertaken.

Answering John Welch

We have now set the ground for our first response to John Welch. No, it is not acceptable for medical graduates with science-based degrees to be allowed to carry on earning considerable sums from some forms of CAM without analysing or acknowledging what they are doing, and all practised with apparent conviction that something unique or specific is being proffered. In so doing they have abandoned science-to what extent depends upon one’s perspective.

If such practice is reasonably widespread, how has this come about? We would argue that the environment into which students are released and the power of particular personalities can override what teachers believe they have inculcated into the minds of their students. In turn this means that the teaching has not been powerful or sustained enough, to carry sufficient clout. In keeping with changes in wider society, students are becoming more demanding of Faculty. Students are demanding more facts and less waffle. ‘Facts’ are equated with ephemeral knowledge, itself a sacrosanct entity which is essential for passing various hurdles. ‘Waffle’ refers to sections of the curriculum devoted to community issues, public health, communication matters and so forth. We are not aware of any satisfactory studies to back our belief that students in general are not particularly interested in lectures on the nature of science or induction into Bayesian concepts to which they theoretically subscribe. We know that many students still believe it is the business of government and administrators to find the money and resources for them to exercise their particular forms of practice, and thus for them to expend those resources freely and independently of audit or censure.

What do patients want?

The concept is abroad amongst some students and younger doctors, that patients always require something tangible from a practitioner and their problems cannot be dismissed without some tangible transaction. Students in turn interpret this as the need for them to manipulate highly visible props for reinforcement of the placebo effect.

When general practitioner incomes fall, offering homeopathy or chelation for a fee becomes attractive, particularly within a culture wherein needs and expectations are being expressed increasingly by members of a public who are increasingly influenced by advertising, non-scientific articles and spurious claims.

CAM at Med School

In the Auckland School of Medicine there are brief sessions devoted to the topic of CAM. The general approach offers the students a broad brush introduction to principles in common forms of CAM, why these appeal to the public, how the efficacy could be judged, and some attention is paid to identifying potential interactions with orthodox medicine. The topic is introduced in Years 2 and 3, and reviewed in Year 5. Given the present situation we believe there is considerable scope for providing a more detailed history of CAM within the curriculum, including scientific criticisms thereof, together with reinforcement at other stages of the course, concerning the nature of the conflict between science and non-science, the role of the doctor’s personality and projection thereof, and what they are contributing to the therapeutic interaction. In the New Zealand Medical Journal of May 2007 Rosemary Wyber and Tony Egan set about elucidating the views and experiences of a group of general practitioners and a group of current junior doctors one or two years out from graduation. To quote: “… A poor relationship with medicine is thought to be an area of considerable unconscious influence of role models. This may contribute to the well documented decrease in idealism during student and early clinical years.”

In the same issue, Tim Wilkinson, the Associate Dean of Medical Education at the Christchurch School of Medicine & Health Sciences, drew attention to the importance of getting the learning environment right. He wrote: “If learning occurs first within an environment of trust and respect … good role modelling will mean effective learning will not be undermined.” This line of reasoning is further reinforced in the same journal by an article by Kathleen Callaghan, Graham Hunt and John Windsor from the University of Auckland. They draw attention to failure of medical training to provide time for exposition of the non-technical aspects of competency.

We agree with their conclusion that professional training programmes need to be radically revised. Professional competency needs redefinition. Such definition must be team-orientated. Attitudes and aptitudes

Of relevance to John Welch’s first question is an issue raised by Callaghan and her colleagues. “Should there be testing of relevant attitudes and aptitudes prior to selection for postgraduate training?” Again, should we select prior to undergraduate training for a wider array of attitudes and aptitudes which would then be integrated and progressively monitored throughout undergraduate training, to ensure a differentiated work force of doctors based on society’s needs? These authors suggest some fundamental questions should include, “What are the patient outcomes that society expects us to deliver?” And “What are the professional competencies required to ensure that these outcomes are achieved?”

Attitudes towards (and use of) CAM in New Zealand were also studied by Poynton and colleagues in the NZ Medical Journal (2006). They found that the number of general practitioners using complementary and alternative medical therapies had decreased but the number referring patients to the unorthodox system had increased. They called for increasing information on CAM to be included in medical education and for attention to earlier research.

A call for reform

A Lancet editorial by Baker in 2005 stated that the time had come to explore the need for a major reform of medical institutions to make them fit to sustain professionalism and respond to the changing expectations of society. In so responding the medical profession and those who educate its entrants needed to have sound perspectives and the ability to challenge some of the false expectations within society. A key point in relation to false expectations is the utilisation of the placebo effect by both orthodox medicine and CAM. When properly handled, there is general recognition that the placebo effect is a boon to busy clinicians and their patients. However, such responses vary considerably between different diseases. Time heals a great deal. Some chronic diseases remit spontaneously. The first thing we educators need to do is to emphasise and demonstrate to students the natural history of disease. In so doing we need to place that in the context of the placebo effect and point out that such effects are notoriously fickle and may occur on one occasion and not on another within the same patient. Use of placebo effects varies across disciplines. We need to point out that large fees are not necessary for inducing a maximum placebo response-but time spent does require reasonable recompense nevertheless.

Scientific medicine and personal influence

Dr John Ellard, a prominent psychiatrist in Australia, has summed it all up in an article entitled, What can be learned from a curing of warts? To quote him: “… in most therapeutic situations there are two important aspects: scientific medicine, and the influence of one person on another. To ignore either is imprudent because the best outcome will be obtained only if both are considered … many remedies work quite well without a scientific basis. My argument is that one should strive for the best of both possible worlds-the greatest benefit from scientific medicine … and the greatest benefit from the healing power of concern for the person. Concern about the disease is not enough”. Moreover, adherence to medication or placebo was associated with lower mortality rates in a Canadian survey of 21 studies; patients’ psyche and personality are very much factors in determining outcomes.

The important point about Dr Ellard’s comment is that the mystique element is removed from the doctor-patient interaction associated with placebo effects. We believe there is no point in studying any mythical homeopathic mechanism, for instance, independent of the placebo effect. Observations of such therapies should be submitted to the same disciplines as evolving treatments in orthodox medicine. They should be controlled for consequences of the passage of time, that is of natural history, observations should be standardised and raw data made available for scrutiny by independent researchers at no extra cost to the subjects of such new (or old) treatments.

Social contracts


In reviewing social contracts much will be required in public education through public involvement and, to some extent at least, through lobbying and other manipulations of the legislature and the legal environment. Increasingly it will be in the interests of our nation as a whole, to review remuneration of time spent by health professionals and what balance should be set between expenditure within essentially a state-run system versus the proportion of national resources expended within an uncontrolled private sector. We believe some curbs will be required in future concerning irresponsible actions within the media, but unless the medical profession and public perceptions alter it will be impossible to develop a common culture and we will all fail together.

Within our present structure of cultures lie the medical students we select for the Otago and Auckland schools. The late Frank Haden pointed out at a previous Skeptics conference in Christchurch: “a doctor told us matter-of-factly that seven percent of the school’s 1997 fifth year students believed in creationism.” There is work to be done. We face an aggressive, burgeoning non-science or anti-science culture. Some of our students lie within awkward subcultures and some enter these after graduation. In finishing, we quote a 1995 Lancet editorial. “The intellectual strength of science lies in its essentially subversive character.” That same editorial quoted Freeman Dyson: “There is no such thing as a unique scientific vision … science is a mosaic of partial and conflicting visions. But there is one common element in these visions. The common element is rebellion against the restriction imposed by the locally prevailing culture.”

To this we can add the conclusion of a paper titled Health Delusions, written by Denis Dutton in 1988. “I am disturbed by a Listener editorial not long ago on the topic of alternative medicine which has gone so far as to call for government funding for fringe medical services. And this editorial ought not to be dismissed as an insignificant aberration: in the present user-pays climate of medical policy decisions it is possible that there will be increased pressure to turn our back on expensive, science-based medicine in favour of popular but worthless pseudoscientific placebos. I think it is imperative that health professionals throughout New Zealand work to resist such pressures. Our stretched public health resources must be directed towards valid, effective science-based care. Anything less will prove expensive and dangerous.”

List of references available from the editor.