Correspondence with the National Institute for Health and Clinical Excellence

This page lists correspondence with the National Institute for Health and Clinical Excellence. On 3 December 2012 BMJ editor in chief Dr Fiona Godlee wrote to NICE's chair, Professor Sir Michael Rawlins. In her letter she says: "Now that serious doubts have been raised about the evidence behind claims for oseltamivir’s effectiveness and safety, I am asking you to withdraw approval for oseltamivir until NICE has received and reviewed the full clinical trial data and those anonymised data are available for independent scrutiny."

 

All rapid responses

Rapid responses are electronic letters to the editor. They enable our users to debate issues raised in articles published on bmj.com. Although a selection of rapid responses will be included as edited readers' letters in the weekly print issue of the BMJ, their first appearance online means that they are published articles. If you need the url (web address) of an individual response, perhaps for citation purposes, simply click on the response headline and copy the url from the browser window.

History repeats itself: the authors of this article from The Netherlands have joined the group of authors who question the positive impact of early detection on advanced cancer rate by repeating the same mistake that we have critiqued so many times; the Dutch colleagues, just like all the other anti-screening authors, lack precise knowledge about each tumor’s detection mode. They admit that “the Netherlands cancer registry registers anonymous population data”, which means that they could not distinguish among cancers detected in women who attended screening (screen detected plus interval cases) and cancers that were detected outside screening. It is certain that the majority of the “early stage breast cancer” in the Dutch study was detected among women who attended screening; on the other hand, it is very likely that the majority of their “advanced stage breast cancers” were patient and physician detected outside screening. Thus, making claims that modern mammography screening has little or no effect in decreasing the advanced cancer rate (or reducing breast cancer death, as other authors concluded) is simply a biased guess.

Yet, despite inadequate data and the resulting unjustified assumptions, all these authors still consider their inaccurate and often flawed estimates worthy of publication. It should be noted that the authors have already observed a significant decrease in advanced cancers as a result of screening, despite the short follow-up time; had they removed the large number of advanced cancers detected among the 27-30% non-attendees, they would have been able to see the desired significant decrease in advanced breast cancer rate in women actually screened, but this requires knowledge about “detection mode” which the authors do not have. In addition, they have not commented on “downward stage shifting” within the Stage II and III categories: both a 12 mm invasive cancer with a single metastasis and a 48 mm invasive cancer with several positive lymph nodes and periglandular growth belong to the same Stage II category, although the two cases will certainly have a different outcome. They have also not cited the relevant literature; an association between mammography screening programs and similar downstaging of breast carcinomas in older women has previously been documented and reported (1-4).

“Mammography-detected breast cancer is associated with a shift toward earlier-stage diagnosis in women 75 years and older, subsequently reducing the rate of more advanced, difficult–to-treat cases”. ”We did observe an increase in early stage breast cancer over time, but this increase was balanced by a decrease in higher-stage disease – exactly what we would hope to achieve in a screening program” (1). Solin LJ et al reported that “Significant downstaging was found for the breast cancers detected in women who had undergone mammographic screening compared to the breast cancers detected in women who had not undergone mammographic screening” (2). Norman et al published that “Mammography screening was associated with lower rates of late-stage breast cancer among both premenopausal (OR = 0.64, 95% CI 0.50-0.81) and postmenopausal (OR = 0.44, 95% CI 0.35-0.56) women”. “With modern mammography in the community, rates of late-stage breast cancer diagnoses are lower in screened compared to non-screened women ages 40 and older” (3). Taplin et al “concluded that enrollment in organized screening is associated with reduced odds of late-stage breast cancer (4). Webb et al found that breast cancer death at all ages occur most often among women who have not undergone screening with mammography (5).

How many more articles will be published without access to accurate data on detection mode and without sufficiently long follow-up? This type of poor research has been a recurring theme during the past decade which harms women and confuses their physicians. This article should not have been published in a peer-reviewed journal.

1. Malmgren JA, Parikh J, Atwood MK, Kaplan HG. Improved prognosis of Women aged 75 and Older with Mammography-detected Breast Cancer. Radiology. 2014 Aug 5:140209
2. Solin LJ, Schultz DJ, Kessler HB, Hanchak NA. Downstaging of Breast Carcinomas in Older Women Associated with Mammographic Screening. Breast J. 1999 Mar;5(2):94-100.
3. Norman SA, Localio AR, Zhou L, Weber AL, et al. Benefit of screening mammography in reducing the rate of late-stage breast cancer diagnoses (United States). Cancer Causes Control. 2006 Sep;17(7):921-9.
4. Taplin SH, Ichikawa L, Buist DS, Seger D, White E. Evaluating organized breast cancer screening implementation: the prevention of late-stage disease? Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):225-34.
5. Webb ML, Cady B, Michaelson JS, et al. A failure analysis of invasive breast cancer: Most deaths from disease occur in women not regularly screened. Cancer. 2014 Sep 15;120(18):2839-46. doi: 10.1002/cncr.28199. Epub 2013 Sep 9.

László Tabár, MD, FACR(Hon)

Competing interests: No competing interests

15 September 2014
Laszlo K Tabar
Radiologist
Department of Mammography, Falun Central Hospital, Falun, Sweden
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Dear Sir,
As the author of this article, I am pleasantly surprised to still be receiving occasional correspondence about it. I would appreciate your updating my email address.

The email address that appears in the article: tzewey@singnet.com
My current email address: tzewey@gmail.com

Thank you
Dr. T W Loong

Competing interests: No competing interests

15 September 2014
Tze-Wey Loong
Family Physician
King George's Medical Centre, Blk 803, King George's Ave. #01-144 S(200803), Singapore
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We were disappointed to read Professor Clark’s defence of the perceived value of the Cancer Drugs Fund ((CDF); feature article published in the BMJ Sept 11th.)

Since the establishment of the CDF there have been concerns (1, 2) that it would undermine NICE, permitting funding of drugs NICE had not yet appraised, as well as those found not to be cost-effective. Since the announcement of the introduction of ‘value for money’ criteria into the CDF drugs’ evaluation, NICE is not only being undermined, but their technology appraisal process duplicated. We believe NICE would dispute the claim that: “[NICE] have enough [clinical trials evidence] to say whether a drug works, but not how well or what effect it has on the patient pathway” - conveniently, there is no evidence that the CDF can do it better since they have yet to try. Sir Andrew Dillon told MPs it ‘makes no sense’ that medication NICE has ruled as not cost-effective is available through the CDF. Professor Clark’s comments that, “we’ll be working going forwards much better with NHS England and NICE” may not be aligned with Sir Andrew’s request for “an alignment of processes and methodologies”.(3)

Professor Clark asserts that the English public feel that cancer is worthy of greater spend than other diseases based on the following: “[The NICE end of life criteria approach] was never challenged…that told me it was in the psyche of English people and…it reflects something that most people agree with”. This is a very flawed argument which assumes that the public understood the opportunity cost associated with the CDF and realised they were preferentially paying for cancer. It is also arguably false according to empirical research.(4) Every pound spent on cancer drugs in the NHS is not spent on another health good. While Professor Clark may claim the CDF was ‘additional’ money, it would be naive to assume that the £20 billion efficiency savings which are consuming the NHS at present, were unrelated to the now £280 million being spent on the CDF.

While Professor Clark congratulates the CDF for reimbursing medicines only at the lowest price proposed for use in the NHS, he is later quoted conceding that, “some companies have seen the CDF as an easy route to funding…because they [pharmaceutical companies] don’t have to drop the price to get CDF approval.” In our paper,(5) we demonstrated that there is greater prescribing of non-cost-effective drugs in England than Wales (without a CDF), with slower adoption of new cost-effective drugs.

Finally, one of the most lamentable features of the CDF has been the lack of quality data collection to steer future decision-making. There has been no request for quality of life, or patient reported outcome measure data. And no attempt so far to address early evidence that suggested that prescribing of chemotherapy through the CDF was of much shorter duration than that expected from clinical trials.(6)

Our message is this: Where is the evidence? We have found no convincing evidence that the English public value cancer above other serious/life-threatening diseases; no convincing evidence that cancer drugs will prolong cancer survival greater than comparable cancer treatments, such as radiotherapy or surgery, in fact the reverse,(7) and where is the evidence that the CDF has provided invaluable data to improve decision-making in chemotherapy? The public preference for cancer over other diseases and for cancer drugs over other treatments has been assumed and we are left with the question: where else might this money have been better spent?

1. Howell J. Return of the postcode lottery Opportunity cost of the Cancer Drugs Fund. British Medical Journal. 2011;342.
2. Thornton S. Return of the postcode lottery Cancer Drugs Fund is not a fair allocation of NHS resources. British Medical Journal. 2011;342.
3. Knapton S. Cancer Drugs Fund makes no sense, says head of drugs rationing body NICE. The Telegraph. 2014 02 Sept Sect. Health News.
4. Linley WG, Hughes DA. Societal views on NICE, cancer drugs fund and value-based pricing criteria for prioritising medicines: a cross-sectional survey of 4118 adults in Great Britain. Health Econ. 2013;22(8):948-64.
5. Chamberlain C, Collin SM, Stephens P, Donovan J, Bahl A, Hollingworth W. Does the cancer drugs fund lead to faster uptake of cost-effective drugs? A time-trend analysis comparing England and Wales. Br J Cancer. 2014.
6. Stephens P, Thomson D. The Cancer Drug Fund 1 year on--success or failure? Lancet Oncol. 2012;13(8):754-7.
7. Foot C, Harrison, T. How to improve cancer survival, explaining England's relatively poor rates. Cavendish Square, London W1G 0AN: The King's Fund and Cancer research UK, 2011.

Competing interests: No competing interests

15 September 2014
Charlotte Chamberlain
NIHR Doctoral Fellow
William Hollingworth
School of Social and Community Medicine, University of Bristol
Canynge Hall, 39 Whatley Rd, Bristol BS8 2PS
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Dr McCartney (1) is to be congratulated on commenting on the futility of the current health checks programme as a public health measure.

Public Health has a worthy tradition of concern with evaluating its activities and taking heed of evidence of effectiveness.It is very sad that one of the most important English public health agencies, Public Health England (PHE), appears to neglect past research or a Cochrane Review (2,) in pursuing this activity which has not been shown to have any effect on either population health or the reduction of health inequalities. Not only does this programme consume considerable resources but there is little effort to determine its effectiveness in either outcome or process terms.

Public Health has always considered that its activities should be independent of political considerations and should influence the health of the public.

1. BMJ 2014;349:g4752
2. BMJ 2013;347:f5227

Competing interests: No competing interests

15 September 2014
Walter W Holland
Visiting professor
LSE Health, London School of Economics and Political Science
Houghton St, London WC2A 2AE
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The issue determining if a patient should be referred to a specialist breast clinic is whether the general practitioner can adequately reassure the patient that they do not have a remediable breast problem, notably a breast cancer. With a lump this is simple. Such reassurance requires triple assessment (clinical, imaging and biopsy) and the patient should be referred. Features from the history such as character of lump, family history or endocrine exposure may be epidemiologically interesting but are of no use in determining the cause of a lump. Information on comorbidity, drug and social history are of more practical value.

The wider problem is a combination of 1)the apparent lack of confidence in breast assessment by GPs (who receive 2 days of undergraduate breast teaching locally) and 2) patient anxiety, in part driven by charity, media and government-sponsored awareness campaigns (which have yet to have been shown to produce an increase in breast cancer diagnosis). This has contributed to an increase in referrals to the specialist breast clinic in Edinburgh of around 4% per year while symptomatic cancer diagnosis has increased by about 2% per year. Currently about 1 in 19 patients referred to our specialist breast clinic has breast cancer. Most patients with breast pain and skin lesions should not need to be seen at a specialist breast clinic but again, this requires the GP to be confident to adequately assess and reassure the patient who is often programmed to seek specialist referral.

General practitioners lacking confidence in clinical assessment of the breast are encouraged to get in touch with their local breast unit and arrange to join us for a few clinics.

Competing interests: No competing interests

15 September 2014
Matthew D. Barber
Consultant Breast Surgeon
Edinburgh Breast Unit
Western General Hospital, Edinburgh EH4 2XU
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Arnott claims that

"In England we have a very clear philosophical basis for the public health legislation that prohibits smoking in enclosed public places. This is based on John Stuart Mill’s harm principle which holds that the actions of individuals should only be limited to prevent harm to other individuals."

This is not true. The smoking ban in, more accurately, non residential buildings and secure mental hospitals, prohibits private smoking clubs, even those staffed on a volunteer basis by their own (smoking) members. Countries which adhere to Mill's philosophy permit smoking in bars staffed only by the bar owner. Currently, at least, the Netherlands is one such country. It should be remembered that the stated purpose of the UK indoor smoking ban is to protect employees - not to protect customers, who may choose to go elsewhere.

Regarding electronic cigarettes: all the debates now taking place are academic, as the UK Government is obliged, in 2016, to adopt into UK law, the EU Tobacco Products Directive. The most important of many restrictions placed on ecigs by the TPD are

1. Liquid strength restricted to 2% nicotine

Around 25% of current vapers - these who smoked 20 a day or more,choose stronger liquid.

2. Refillable devices only permitted where there is no possibility of leakage.

This is impossible to achieve and so all refillable devices currently on sale will be banned.

The inevitable consequence of the TPD is that only disposable cartridge "cig-a-like" devices will be available. For the ex 20 a day smoker, these cost about around £50 a week to run, compared with £8 for refillable devices using ready mixed liquid, or £3 using liquid home-mixed from 7.2% nicotine concentrate.

In view of the TPD, the Tobacco Control Industry can choose to be as generous, or vindictive, as it wishes towards vapers. The outcome will be the same.

Competing interests: No competing interests

15 September 2014
Jonathan H Bagley
Lecturer in Mathematics
School of Mathematics, University of Manchester
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National Institute for Heath and Care Excellence (NICE) updated Guidelines (CG175) on prostate cancer in January 2014 1. The guideline does not address the issue of men who present with a raised Prostate Specific Antigen (PSA) in primary care who are symptom free and are not referred for further investigation.

The guidelines cater for PSA follow-up and kinetics with shared care protocols during active surveillance. Guideline 1.3.46 advises that serial PSA levels should be measured using the same assay technique. To quantify biochemical relapse, guideline 1.3.51 recommends that PSA doubling time should be estimated based on a minimum of 3 measurements over at least six months 2.

PSA exists in multiple isoforms and is measured by immunoassay on many platforms. Calibration standards differ with Hybritech calibrated assays giving values about 20% higher than the WHO IRP 96/670 standard for the same sample. Combining biological variation with an analytical variation of 5%, a difference greater than 20.5% is needed to be sure of real change in the PSA value and the 95th percentile critical difference is 45.8%. A single laboratory should be used for all PSA estimations on an individual patient to reduce false positives in disease monitoring. This should be included explicitly in NICE guidelines on prostate cancer treatment 2.

References
1. http://www.nice.org.uk/Guidance/CG175 (accessed 14th September 2014)
2. Graham J, Kirkbride P, Cann K, Hasler E, Prettyjohns M. Prostate cancer: summary of updated NICE guidance. BMJ. 2014 Jan 8;348:f7524. doi: 10.1136/bmj.f7524.
3. Tormey WP. The complexity of PSA interpretation in clinical practice. Surgeon. 2014 Jul 2. pii: S1479-666X(14)00051-1. doi: 10.1016/j.surge.2014.04.003.

William P. Tormey
Department of Chemical Pathology
Beaumont Hospital,
Dublin 9
Ireland
billtormey@gmail.com

There are no competing interests.

Competing interests: No competing interests

15 September 2014
William Tormey
Consultant Chemical Pathologist
Beaumont Hospital
Dublin 9, Ireland
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The paper by Hunt et al has clearly sparked long overdue interest in the subject of b12 deficiency and surprise at the unreliability of the serum b12 test.

It may be worth looking closer into three issues: firstly, what were the deficient levels intended to identify? A brief look back at history in the 1940s and 50s shows that pharmaceutical companies interests were related to the identification and treatment of anaemia. A condition, which at the time was believed to precede neurological damage. Yet in the 1960s the metabolic functions of b12 were established and indicated that the neurological damage most likely would precede the anaemia. Yet were the deficient ranges adjusted accordingly?

The second issue relates to treatment and returning the serum b12 levels to normal. Even back in 1926 this was, in respect of the anaemia, recognised as being a symptom that was quickly and easily treated. Yet even then (at a time when the anaemia was thought to precede the neurological damage) the nerve damage proved difficult to treat and reverse fully even with intensive care and treatment. In short, returning a patient's b12 levels to within the normal range has no relationship to whether or not the neuro damage has been resolved.

Indeed it would be interesting to note how the serum b12 test or any other, could establish what cellular damage has taken place and if and when that damage is rectified. Thus a patient needs to be treated according to symptoms.

Finally, treatment protocols in the UK are lacking comparative to most developed nations. Admittedly the UK use hydroxocobalamin rather than cyanocobalamin, but surely this does not warrant patients having to wait two months longer than those in France or the US, for a maintenance dose?

So, when it comes to GPs reporting that their patients are not deficient - is that assertion made relative to whether or not their patients have deficient serum b12 levels? Should that level be raised how many more would have symptoms attributed to a deficiency. Or, if another, more reliable test relative to possible neurological injury, came into common usage, would the percentage reported by GPs go up substantially?

Competing interests: No competing interests

15 September 2014
K Thompson
Self Employed
France
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Self-harm is prolific and protean. Its self-deceptive, sadomasochistic manifestations include injuries, accidents, addiction, tattoos, body-piercing, promiscuity, infidelity, fanaticism, cruelty, crime, violence, and suicide. What should we do? We should understand that we all have both a life wish (libido) and a death wish (mortido). And we should be alert to the mortido, because it never rests, and it’s always with us. 


Competing interests: No competing interests

14 September 2014
Hugh Mann
Physician
Retired
New York, USA
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Whilst doctors and patients mostly aim for and achieve a joint understanding on diagnosis and treatment, this may not always be possible.

General Medical Council Good Medical Practice Guidance states: "If you feel your doctor has not made the right diagnosis or is not offering the right treatment, you can ask for a second opinion from another doctor." (1) This also gives advice on when to obtain a second opinion in situations of end of life care; or suggest a second opinion in situations where a patient requests a treatment that the doctor considers would not be of benefit.

In instances where a patient does not ask for a second opinion, but does not agree with a diagnosis or treatment, and the therapeutic alliance is at risk of breaking down, it may sometimes be helpful for a consultant to ask whether a patient would agree to a second consultant opinion. Consideration should be made whether this should be a doctor based on a different team, possibly elsewhere - if that is an option; and whether this is to take over care if the opinion is different.

Such second opinions suggested by a consultant may facilitate a positive solution to a disagreement, potentially decrease the risk of a complaint, and allow subsequent peer discussion and review with the doctor giving the second opinion.

Peter Simmons
Consultant Psychiatrist

(1) Good medical practice (2013). General Medical Council. http://www.gmc-uk.org/guidance/21774.asp (accessed 14 September 2014)

Competing interests: No competing interests

14 September 2014
Peter Simmons
Consultant Psychiatrist
Rosanne House - 2nd floor, Parkway, Welwyn Garden City, Hertfordshire. AL8 6HG
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