Dear Philipp,
What about Proton Beam Therapy? That is rapidly on its way to becoming the next white elephant in the treatment options for early prostate cancer. And these treatment options are all a fallout of the original PSA test.
There are already seven such hugely expensive centres in the USA and now UK oncologists have also decided that they too want atleast one such unit in the UK. Each UK centre will cost about 140 million pounds to set up, with annual revenue costs for NHS commissioners expected to be a further 50-100 million pounds to treat 1500 cases annually. No one has bothered to do any sums as to where all this money will come from, in the light of the NHS entering into a frozen financial tundra very soon.
We recently did a rapid review of the evidence around proton beam therapy and were appalled at the lack of any robust evidence around treatment of oncological conditions with proton beam therapy. This again ties in with Ben's email about policy makers and guideline developers ignoring systematic reviews and meta-analysis.
I'm cutting and pasting a summary of our rapid evidence review here, for you and others to have a read:
Evidence of Clinical Effectiveness
1. Very recently, in September 2009, AHRQ (the US
Government Agency for Healthcare Research and Quality published an evidence
brief on proton beam therapy.
It categorically states:
It is very likely that, as this technology
becomes increasingly available, it will also be increasingly used with much
broader indications. This anticipated diffusion of the technology can have
important implications (economic, regarding prioritization of resources, and
potentially on health outcomes). Especially for many common cancers, such as
breast, prostate, lung, and pancreatic cancers, it is essential that the
theorized advantages of particle beam therapy vs. contemporary alternative
interventions are proven in controlled clinical trials, along with concomitant
economic evaluations.
View Executive Summary as PDF
Particle Beam Radiation Therapies for Cancer
Final Technical Brief
Final
Research Review (PDF)
Final
Appendices (PDF)
The AHRQ summary brief for policy makers
clearly states:
Particle beam radiation therapy(PBRT)
is an alternative to other types of radiation therapies for treating cancer.
This summary reviews the different types of PBRT, their potential advantages
and disadvantages, and their current uses. At present, there is very limited
evidence comparing the safety and effectiveness of PBRT with other types of
radiation therapies for people with cancer. Therefore, it is not possible to
draw conclusions about the comparative safety and effectiveness of PBRT at this
time.
Policymaker Summary Guide
2. In 2008, the Singapore HTA Programme
reviewed proton therapy:
http://www.singhealth.com.sg/NR/rdonlyres/1E7AAD9E-9E50-4C18-8A81-ECF143D1EA8F/10291/PBT.pdf
The findings of the report were: While Proton
Beam Therapy (PBT) appears to be promising, the technology has not been fully
tested, as comparative studies are few
3. In 2007,
a systematic review of the clinical effectiveness for proton therapy by
Olsen et al for the Norwegian Knowledge Centre for Health Services concluded
that 'The evidence on clinical efficacy of proton therapy relies to a large
extent on non-controlled studies, and thus is associated with low level of evidence
according to standard heath technology assessment and evidence based medicine
criteria':
http://www.dsko.org/files/ParticleNorskanalyse.pdf
4. In 2007, a systematic review of the
clinical and cost effectiveness of hadron therapy in cancer by Lodge et al
concluded that ‘no firm conclusions about clinical or cost-effectiveness of
proton therapy or of C-ions could be drawn’:
https://espace.cern.ch/partnersite/Bibliography%20on%20Hadron%20Therapy/History%20and%20Literature%20Reviews%20on%20HT/LODGE-A%20systematic%20Literature%20review%20of%20the%20clinical%20and%20cost-effectiveness%20of%20hadron%20therapy%20in%20cancer.pdf
5. The 2007 issue of the Australian and New
Zealand Horizon Scanning Network (ANZHSN) Bulletin on the topic states:
However, it is unclear if proton beam therapy
for uveal melanoma results in a substantial improvement of eye
preservation rates and the ocular complications observed post-treatment are of
concern. Further studies are required to address the flaws of previous studies
and to compare proton beam therapy to existing techniques.
AND
In conclusion, the evidence for proton beam therapy in
neoplasms involving, or adjacent to, cranial structures
remains inconclusive. Further studies are required to determine if proton
therapy is indeed substantially better compared to conventional radiotherapy,
as inferred by numerous treatment planning studies.
http://www.health.gov.au/internet/horizon/publishing.nsf/Content/FCA3C530CC5EDC91CA257244007B32CD/$File/FINAL%20ANZHSN%20Bulletin,%20Issue%203.pdf (Pages 3 and 4 of
pdf copy).
The full horizon scanning reports can be
accessed online at:
Proton beam therapy for the treatment of neoplasms involving
cranial structures (May 2007) (PDF 971 KB)
Proton beam therapy for the treatment of uveal melanoma (May
2007) (PDF 740 KB)
6. A 2007 Review article ‘Proton Therapy in
Clinical Practice: Current Clinical Evidence’ by Brada et al makes similar
observations to those made by the other systematic reviews:
http://jco.ascopubs.org/cgi/content/full/25/8/965?ijkey=264b01950bd3c41d0125e9e48905b8a317797cd1&keytype2=tf_ipsecsha
7. Brada et
al, writing in the Journal Of Oncology in 2008, make the following assertion:
The consumer
representatives have been influenced by informationthat mostly
originates from proponents of protons with frequentcommercial
interest in the new equipment. Such reports are subjectto
understandable bias and conflict of interest with few qualmsabout
overstating the available evidence. The current spateof systematic
reviews tries to redress the balance. In the lightof the overall
agreement of lack of existing clinical evidencefor benefit of
protons, to demand that at least some of theclaims are
substantiated does not seem too much to ask. Randomizedcontrolled
trials in the absence of level 2 evidence at thisstage may be
excessive, and outcome from well designed prospectivephase II
studies, away from commercial influence and focusingprincipally on
toxicity end points, would be a good start. Eventhe Institute of
Medicine, part of the US National Academicof Science, is in favor
of knowing what works (www.iom.edu).
Finally,
regarding cost—yes, Morgan can travel acrossthe oceans in a new
rocket-propelled plane, and yes, do notask us to pay for it. If the
plane actually gets him to theland destination faster, we may pay.
http://jco.ascopubs.org/cgi/content/full/26/15/2592-a
Evidence of Cost Effectiveness
1. Maastricht; 2008(The Netherlands) PMID 18707784-- "Cost-effectiveness of
particle therapy: Current evidence and future needs." (Pijls-Johannesma M,
Radiother Oncol. 2008 Nov;89(2):127-34. Epub 2008 Aug 15.)
* Literature review of cost and cost-effectiveness of proton therapy
* Outcome: Literature scarce, non-comparable, and not performed according to standard health technology assessment criteria
* Conclusion: Model-based economic evaluations may help gain evidence-based insight into cost-effectiveness
2. Fox Chase; 2007 PMID 17704408 -- "Is proton beam therapy cost effective in the treatment of adenocarcinoma of the prostate?" (Konski A, J Clin Oncol. 2007 Aug 20;25(24):3603-8.)
* Markov model. Cost-effectiveness evaluation of 91.8 CGE proton beam vs. 81 CGE photon IMRT, using cost, bNED, utility data
* 15 year model: 70 year old: cost of protons $63,500 vs. IMRT $36,800; 60 year old: protons $65,000 vs. photons $39,400. Incremental cost/QALY 70-year old $63,6000 and 60-year old $55,700
* Conclusion: Assuming 10 Gy additional dose-escalation, proton beam not cost-effective for most patients
* Editorial (PMID 17704400): PT legitimate form of EBRT for prostate cancer, but if dose escalation cannot be achieved over existing therapies, economic utility relies on clear and meaningful difference in quality of life. This area should be investigated urgently
3. Yale; 2007PMID 17500444-- "Point/counterpoint.
Proton therapy is too expensive for the minimal potential improvements in
outcome claimed." (Schulz RJ, Med Phys. 2007 Apr;34(4):1135-8.)
4. Lundkvist J, Ekman M, Ericsson SR, Jonsson B, Glimelius
B.Cost-effectiveness of proton radiation in the treatment of
childhood medulloblastoma. Cancer 2005; 103: 793–801
This is the only health economic article that claims that proton
beam therapy is cost-effective, and the only economic basis on which NCG wants
to commission proton-beam therapy, but the economic analysis is flawed
The analysis
looks at four cancers - and the ICERs are very different, (see below). This
means that the cost effectiveness is
highly dependent upon casemix.
It looks like there is absolutely no cost-effectiveness for medulloblastoma and
head-neck cancer. However, it is nowhere near cost effective for breast cancer
and probably not cost effective for prostate cancer.
The other problem with this analysis - the
sensitivity analysis is very simplistic. Given the title of the
paper is 'Proton therapy of cancer: Potential clinical advantages and
cost-effectiveness' one would have expected quite detailed consideration of the
uncertainty in this analysis. It simply isn't there.
The models maximise the potential
benefit by extrapolating benefits assuming a life expectancy of 100 years.This is probably not defensible, unless this is the life expectancy in Sweden.The costs are rather old (2002)
and updated using the consumer price index rather than the relevant health
price index.One is not sure what difference this would
make, but its not good practice.The
cost of a proton facility is low compared to the figures quotes for the UK -
62.5 million euros.The life expectancy for the facility is set at 30 yearsrather than the normal 25. Both of these push down the expected cost per
case of the facility.
The assumptions are generally very generous nature and serious questions need
to be asked as to whether this paper
would be accepted in a UK decision-making setting.
Breast cancer
Average breast cancer patient 66 608
High risk population (assuming double risk of cardiac disease) 34 290
High proton radiation cost estimate** 94 282
Low proton radiation cost estimate *** 60 757
Prostate
cancer
Standard case results 26 776
High proton radiation cost estimate** 35 304
Low proton radiation cost estimate *** 24 727
Head-Neck
cancer
Standard
case results 3811
High proton radiation cost estimate** 6305
Low proton radiation cost estimate *** 3225
Medulloblastoma
Standard case results Dominates
High proton radiation cost estimate Dominates
Low proton radiation cost estimate Dominates
Regards,
Ash
Dr Ash Paul
Medical Director
NHS Bedfordshire
21 Kimbolton Road
Bedford
MK40 2AW
Tel no: 01234795705
Email: [log in to unmask]
________________________________
From: "Dahm, Philipp" <[log in to unmask]>
To: [log in to unmask]
Sent: Sun, 4 April, 2010 15:55:12
Subject: Re: Do you know good examples where guidelines ignore evidence?
Dear Paul:
The American Cancer Society recently released a position paper on PCA screening; they are a lot more reserved than the AUA (also a position paper that updates a recent "Best Practice Policy Statement")
The there is of course recent guidance of the USPTF that explicitly recommends against PCA screening in the elderly.
Another maybe even better example that relate to prostate cancer relates to the use of total androgen ablation (TAB; i.e. combination of orchiectomy/LHRH analog or antagonist + an anti-androgen) for metastatic prostate cancer. There are multiple SRs that suggest that any benefit of adding an anti-androgen adds at best a marginal benefit with regards to overall and disease specific survival. Nevertheless, guidelines such as those by ASCO state that it should be "considered". The Chinese guidelines do not provide explicit recommendations for anything, but actually appear to encourage the routine use.
I wonder has anybody done a systematic study looking at how methodological rigor of guidelines is associated with recommendations that appears to contradict existing evidence?
In know there is NIH R0-1 funded grant project ongoing by one of the GRADE members looking at recommendations and COI of guideline panelists.
Ph*
Philipp Dahm, MD, MHSc, FACS
Associate Professor of Urology, Associate Residency Program Director & Director of Clinical Research
Department of Urology
University of Florida
College of Medicine, Health Science Center
Box 100247, Room N2-15
Gainesville, FL 32610-0247
Phone: (352) 273-7936
Fax: (352) 273-7515
Email: [log in to unmask]
Website: http://evidence-based.urology.ufl.edu
This communication may contain information that is legally exempt from disclosure. If you are not the intended recipient, please note that any dissemination, distribution or copying of this communication is strictly prohibited. Anyone who receives this message in error should notify the sender immediately by telephone, or by return email and delete the message from their computer.
-----Original Message-----
From: Evidence based health (EBH) [mailto:[log in to unmask]] On Behalf Of Paul Glasziou
Sent: Sunday, April 04, 2010 5:48 AM
To: [log in to unmask]
Subject: Re: Do you know good examples where guidelines ignore evidence?
Dear Lilya
The NICE guidelines I found (CG58 - Prostate Cancer Diagnosis and
Treatment) seems to skirt around the issue of PSA screening or case
finding but starts at the decision to have a biopsy!
"To help men decide whether to have a prostate biopsy, healthcare
professionals should discuss
with them their prostate specific antigen (PSA) level, digital rectal
examination (DRE) findings
(including an estimate of prostate size) and comorbidities, together
with their risk factors
(including increasing age and black African and black Caribbean
ethnicity) and any history of a
previous negative prostate biopsy. The serum PSA level alone should not
automatically lead to
a prostate biopsy."
Is there another guideline on PSA? I also note this was February 2008 -
and the 2 large RCTs of screening published in March 2009.
Seems guideline writers have an uphill battle keeping long guidelines up
to date!
Thanks
Paul Glasziou
Liliya Bakiyeva wrote:
> NICE guidelines on prostate disease - completely out of tune with the
> evidence on PSA testing & monitoring.
> NICE guidelines on ECT - only recommend it as a "last resort"
> treatment and seemingly ignore all the evidence supporting ECT's
> efficacy in severe/psychotic depression. Did I mention that these
> guidelines were put together without any psychiatrists on board?
>
> On 3 April 2010 19:54, Fell Greg <[log in to unmask]
> <mailto:[log in to unmask]>> wrote:
>
> CG96 - chron neuropathic pain
> Section on pregabalin seems like it was written by Pfizer. Seems
> to completely ignore the cochrane reviews - from which one might
> infer that gabapentin is just about equally effecacious (oh and
> much cheaper).
> That recommendation will cost taxpayers at least £0.5m in our
> district alone (500k people) - by directing to pregab when
> gabapentin might do. Seems like a case of accepting 'a little bit
> less health for an awful lot less brass'
>
> Why?
> Long arm of pharma influence?
>
> Over emphasis on expert opinion (which can be biased or unbiased)
> and under emphasis on evidence?
>
> Underemphasis on resource impact of recomentations. NICE is not
> responsible for assessing and dealing with the opportunity cost of
> its recomendations
>
>
>
> Greg Fell
> 07957 144899
>
> ----- Original Message -----
> From: Evidence based health (EBH)
> <[log in to unmask]
> <mailto:[log in to unmask]>>
> To: [log in to unmask]
> <mailto:[log in to unmask]>
> <[log in to unmask]
> <mailto:[log in to unmask]>>
> Sent: Sat Apr 03 17:00:38 2010
> Subject: Do you know good examples where guidelines ignore evidence?
>
> Dear All,
> Do you have examples of guidelines that appear to ignore or contradict
> evidence? For example, self-monitoring of blood glucose has been
> recommended by many guidelines (including ADA and NICE guidelines in
> 2008) despite weak evidence, and in 2007 the DiGEM trial[1] which
> pretty
> clearly showed no benefit (and perhaps some harm). We are particularly
> interested examples that might help us understand *why* some
> guidelines
> appear to ignore evidence, but we'd also be interested in studies that
> simply document the extent to which guidelines use best evidence, e.g,
> Andy Oxman's 2007 review of WHO guidelines showing that "Systematic
> reviews and concise summaries of findings are rarely used for
> developing
> recommendations." [2]
> Many thanks
> Paul Glasziou & Chris Del Mar
> 1. Farmer A et al Impact of self monitoring of blood glucose in the
> management of patients with non-insulin treated diabetes: open
> parallel
> group randomised trial. BMJ. 2007 Jul 21;335(7611):132. Epub 2007
> Jun 25.
> (The ADA guidelines were "revised October 2007, published 2008 but do
> not mention the July 2007 trial; the NICE guidelines mention DiGEM but
> state it was not published at the time of writing).
> 2. Oxman AD, Lavis JN, Fretheim A. Use of evidence in WHO
> recommendations. Lancet. 2007 Jun 2;369(9576):1883-9.
