Linda Bryder responds to an article in our last issue.
The article by Michelle Coffey (NZ Skeptic, 97) restates the conclusions of the Cartwright Report which are not, as she seems to imply, unassailable facts. Indeed many of the points Coffey highlights are contestable and have been effectively contested. Some examples (Coffey’s statements in italics) are as follows:
“The report found that Green… aimed to prove a point that even at the time was known not to be the case. A 1961 compilation of studies…showed CIS progressed to invasive cancer in 28.3 percent of cases.”
There was no medical certainty about the proportion of cases of CIS which would advance to invasive cancer, either in 1961 or subsequently. In 1976 the British Medical Journal described this very question as a “fierce controversy”.1 Studies, with accompanying disagreements relating to appropriate treatment, continued throughout the period under discussion. In 1993 an Australian researcher reviewed all the studies of the progression of CIS that he could find since 1955. He commented on how controversial it was. He concluded that the studies showed the invasive potential of CIN1 to be 1 percent, CIN2 to be 5 percent and CIN3 or CIS to be 12 percent or possibly more.2 The reality was even more complicated, as pathologists constantly disputed the allocation of dysplasia into the various grades of CIN1, 2 and 3. As American professor of gynecology Leopold Koss stated in 1979, “Truly it can be repeated that one man’s dysplasia (CIN1( is another man’s carcinoma in situ (CIN3).”3
2 “Standard treatment of the time involved excising all affected tissue and the ‘conservative’ treatment conisation was in use well prior to 1966.”
Coffey cites 1958 “official policy”, as did Judge Silvia Cartwright, to show this. This National Women’s “official policy” was agreed to at a meeting of only nine senior consultants (including one paediatrician) with two dissenting voices.4 Many doctors, in New Zealand and overseas, still opted for the more invasive hysterectomy as treatment for CIS. A 1983 study noted that in the USA hysterectomy had been the most common treatment since the 1950s.5 In fact Coffey acknowledges this variation in preferred treatments in the next paragraph when she writes, “During this period, some centres were beginning to use cone biopsy as effective treatment; however there were limitations to its use.”
3. “Cartwright concluded that Green’s 1966 proposal was a ‘research proposal’.”
Professor Barbara Heslop explained this more appropriately in its historical context when she wrote: “The investigation was basically a collection of clinical cases whose attributes were to be reported retrospectively.” 6 Green certainly planned to publish in international medical journals (he had an academic post which held expectations of scientific publications) but he was, as Professor Heslop wrote, a “clinical collector”. He himself used the term “medical cartography” to describe his research.7 Sir William Liley told Green in 1975:”Your dogged long term data collection lacks the instant appeal of some of the other exploits about the place.”8 Green was first and foremost a gynaecologist however, and as American professor of bioethics, Robert Baker, wrote of the 1960s, it was presumed at that time that “the therapeutic relationship would automatically predominate over the scientist”subject relationship.”9 That certainly applied to Green.
4. “In addition, patients over the age of 35 were included in the research in breach of the protocol.”
The 1966 management protocol was to “extend” conservative treatment to all those under the age of 35, which did not mean that such management was restricted to that age group. Indeed, the protocol shows the extent to which clinical decisions predominated over any research objectives. The conservative treatment regime was extended to cover at least all young women, who could be most harmed by excessive intervention, but it was never intended that conservative treatment would only apply to young women; the choice of treatment was done on a case”by”case basis.
5. ” Patients also had to return for repeated tests and other invasive procedures.”
Coffey presents this as a negative outcome, as though it was an unnecessary encumbrance for the women. However, in her recommendations, Judge Cartwright (p 210) wrote: “Any woman who has received a diagnosis of CIS … must have her condition monitored for life.”
6. “… new”born babies had their vaginas swabbed without formal consent from the parents.“
Regarding the infant vaginal swabs, a press release by Judge Cartwright’s counsel stated “Mothers were told of the tests.” In her report, Cartwright commented on the lack of consent.10 By this she must have meant written consent. Yet oral consent was also the format for Sir William Liley’s intra”uterine blood transfusions from the early 1960s and Sir Graham Liggins’s infusion of corticosteroids from the late 1960s, at the same institution, which were internationally acclaimed. These need to be placed in the context of the times. Similarly the trial of radiotherapy and hysterectomy for cervical cancer, initiated in 1972, which Coffey refers to, complied with international practice for randomised controlled trials and the principle of equipoise.11
7. “The patients were divided retrospectively into two groups which overlapped strongly but not completely with groups defined by Green, that he called ‘special series’.”
Despite writing this, Coffey herself makes it clear that the two groups created by Dr Bill McIndoe et al in 1984 (numbering 817 and 131) had nothing to do with the two groups whose records Green analysed (numbering 27 and 25).
8. “While Coney and Bunkle may have made a mistake [thinking there were two groups], it’s clear the judge didn’t.”
Judge Cartwright most definitely accepted Coney and Bunkle’s interpretation; on page 95 Cartwright wrote:
“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 the women in the limited treatment group were twelve times more likely to die as the fully treated group” [my italics].
Cartwright accepted this as “accurately reflect[ing] the findings of the 1984 McIndoe paper.” She therefore accepted unequivocally that there were two groups, one of which had “limited or no treatment”.
9. “… the proportion of invasive cancer in those inadequately treated was much higher compared with those who had returned to negative cytology”.
How had they “returned to negative cytology”? There is no evidence that their treatment was any different from the others (indeed McIndoe himself told Coney that treatment did not enter their study12) but their disease had disappeared. The distinction was not “inadequately treated” and “adequately treated”, but rather “positive cytology” and “negative cytology”. The McIndoe paper stated: “The 131 patients in group 2 continued to produce abnormal cytology …irrespective of the initial management or the histologic completeness of excision of the lesion”.13
10. “… 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…”
Coffey refers to the 1986 paper on carcinoma of the vulva as critical of conservative treatment, yet overlooks the conclusion of this paper which advised caution in treatment: “Although a small proportion of recurrences will occur, mutilating vulvectomy [should be] avoided.”14 Coffey actually confuses the two studies (1984 and 1986), when she reverts to a discussion of the 1984 McIndoe paper.
11. “CIS is and was a totally curable lesion.”
Would a modern gynaecologist agree with this assessment? If so, how does one explain that cervical cancer has not been eliminated from our population? Indeed the McIndoe paper stated: “Thus, whether or not the lesion is completely excised does not appear to influence the possibility of invasion occurring subsequently.”15
12. “evidence of continuing disease, demonstrating that the intervention was inadequate… this differs from group 1 patients, who were successfully treated at the outset.”
As stated above, Group 1 and Group 2 had a similar range of treatments, the differences did not relate to treatment but rather whether or not they had continuing disease.
13. “This paper [McCredie et al. 2008] 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 methodology of the 2008 paper has been questioned by Sandercock and Burls, who wrote: “This paper states clearly that the authors divided their sample into adequately and inadequately treated groups. However, a major problem in their methods is that they use the outcome following treatment as part of the classification system.” Sandercock and Burls cite the 2008 paper:
“Any procedure followed by a positive smear in the following 6-24 months was classified as inadequate treatment (Figure 1). Four women who developed cancer within 2 years of CIN3 diagnosis, but who had no follow-up cytology, were assumed to have had inadequate treatment.”
Sandercock and Burls comment that: “Given that they partially base the classification of adequacy of treatment on outcomes, it is totally unsurprising and uninformative that the authors should find that women who are classified as ‘inadequately treated’ have poorer outcomes. It is difficult to follow exactly what this paper was trying to prove, but as a means to demonstrate that conservative treatment led to worse outcomes, the methods are wholly inadequate.”16
14. “This study [McCredie 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.“
Apart from the questionable methodology referred to above, it should also be noted that a study on outcomes cannot make such pronouncements on what the intentions were of those who managed the women’s conditions.
15. “[Green’s] ‘atypical’ viewpoint was also promoted in the scientific literature and in the press, creating confusion within the medical scene and with the public.“
For Coffey this included undergraduate and postgraduate medical students. Yet Green’s achievement was to encourage an openness to look at the evidence. In this, he followed Thomas McKeown, the British Professor of Social Medicine who questioned the role of modern medicine by studying data on causes of death over a 200- year period (this included a questioning of the role of cervical screening).17 Far from creating confusion, Green’s willingness to debate the evidence and to question modern medicine and technological interventions is exactly what a modern democratic society should seek to promote, and this should certainly be a goal of the Skeptics Society.
- Leading article 1976: BMJ 2, 659-60.
- Östör, AG 1993: Intern. J. Gyn. Path. 12, 2, 1993, 186-92.
- Koss, LG 1978: Obstet Gynecol. 51, 377.
- Bryder, L 2009: A History of the ‘Unfortunate Experiment’ at National Women’s Hospital, Auckland University Press, Auckland.
- Larsson, G 1983: Acta Obstetricia et Gynecologica Scandinavia, Supplement 114, Lund, 9-10.
- Heslop, B 2004: NZMJ 117, 1199 (www.nzma.org.nz.ezproxy.auckland.ac.nz/journal/117-1199/1000).
- Cited in Bryder, 128.
- Cited in Bryder, 88.
- Baker, R 1998: in cooperation with Herych, E (eds), Ethics Codes in Medicine: Foundations and Achievements of Codification since 1947, Ashgate, Aldershot, 322-4.
- Bryder, 132-3.
- Bryder, 71-2.
- Bryder, 33.
- McIndoe, WA; McLean, MR; Jones, RW; Mullins, PR 1984: Obstet Gynecol. 64, 4, 454.
- Jones, RW; McLean, MR 1986: Obstet Gynecol. 68, 4, 499-503.
- Mcindoe et al, 457.
- Sandercock, J; Burls, A 2010: NZMJ 123, 1320; ISSN 1175 8716, 119. (www.nzma.org.nz/journal//123-1320/4280/)
- McKeown, T 1976: The Role of Medicine: Dream, mirage or nemesis? Nuffield Provincial Hospitals Trust, London
- McKeown, T; Knox, EG 1968: ‘The Framework Required for Validation of Prescriptive Screening’, in McKeown, T (ed.), Screening in Medical Care: reviewing the Evidence: A collection of Essays, Nuffield Provincial Hospitals Trust, Oxford University Press, London.