Dear Piersante,
 
Richard Saitz from our Group wrote a great Blog in BMJ Evidenced-Based Medicine Blog on this subject (incidentally, as healthcare commissioners, we are all now coming under enormous pressure to publicly fund all this - no one thinks to ask us where we will get the money from, or from which existing funding pot we will withdraw the money from, in order to fund this).
 
My only criticism of Richard's great article, is that Richard as a Prof of Public Health, does not explicitly mention anywhere that all screening programmes need to meet Wilson-Jungner's criteria for screening (as a public health service), and this trial certainly doesn't answer all the WJ questions.

Universal screening with computed tomography for lung cancer? Finally a randomized trial…but what to do??

11 Jul, 11 | by Dr Richard Saitz, Editor of Evidence-Based Medicine
 
 
Expert opinion and observational studies have favored lung cancer screening but trials (of plain xrays) have not shown benefit, until now. For years, many have been asking for a randomized trial. Now that the results of the (US) National Lung Screening Trial (NSLT) have been published, it reminds me of the admonition to “be careful what you ask for, you just might get it.”
 
The randomized trial compared three screenings, either low dose CT scans or plain chest radiographs and adherence to the screening protocol was >90%. How to address a positive test was left to clinicians outside the trial. It enrolled 53 454 participants age 55-74, who smoked at least 30 pack-years currently or who had quit in the past 15 years, and had not had lung cancer or a recent chest CT scan, hemoptysis or unexplained weight loss. The authors estimate only 7% of US current or former smokers would meet these criteria. So the study results do NOT apply to 93% of smokers. One wonders though, to whom they will be applied (paying customers?).
 
What were the results? Amazingly, despite the publication source (New England Journal of Medicine, http://bit.ly/qKs6Lq) and widely agreed upon reporting guidelines, the main results are presented as relative reductions, making them seem large (a 20% decrease in death from lung cancer). I don’t mean to minimize though, just to be clear—it is important that there was a reduction, and more lung cancers were diagnosed in the (low dose) CT group, which had fewer lung cancer deaths. The absolute reduction was the difference between 356 lung cancer deaths in 144,103 person-years in the CT group and 443/143,368 in the plain x-ray group. The absolute risk of lung cancer death among those screened at least once was 1.3% in the CT group, 1.6% in the x-ray group, an absolute risk reduction of 0.312%, for a number needed to screen with 3 tests of 320 to prevent 1 lung cancer death over 7 years. Overall mortality was also reduced (by 0.5%). Complications of evaluation of a positive test were 1.4% in the CT group, 1.6% in the x-ray group.

The vast majority of positive tests were false positives (96% in the CT group, 95% in the x-ray group).
 
None of this addresses long term cumulative population harms from radiation exposure or any impact on likelihood of quitting smoking.
What to do? Many may reach different conclusions depending on the presentation of the results. Others will take these results and then add patient values and preferences. Others still may wish to wait to see the cost effectiveness analyses.
 
What will you do? You now have the evidence…
 
Regards,
 
Ash
Dr Ash Paul
Medical Director
NHS Bedfordshire
21 Kimbolton Road
Bedford
MK40 2AW
Tel no: 01234897224
Email: [log in to unmask]
 


From: Piersante Sestini <[log in to unmask]>
To: [log in to unmask]
Sent: Saturday, 13 August 2011, 4:34
Subject: Re: Something else does indeed need to be done

Thanks to all for this beautiful summer thread.

I stand on the same line as Stephen Senn

I agree that the problem must be tackled, but first we need see what the problem is.

We are talking about narrative reviews.
These are commentaries which need to be written by experts in the field.
To be an expert of research, someone must have practice of research.
For a number of reasons (normative, financial and practical), it is almost impossible nowadays to conduct independent research
Therefore, to become an expert one must somehow depend on industry funds.

The choice then is between having reviews written by somebody with some linkage (and dependency) from the industry, having them written by someone who has little idea of what is writing about, on having no reviews at all.

I clearly prefer the first hypothesis. I also agree that full disclosure is imperative and that it is not enough.

There is another fallacy that hasn't be mentioned: the "ad hominem" fallacy. That is, to judge *who* say something or *why*, rather than the *arguments* that s/he  put forwards.

To judge the plausibility and the fairness of the arguments is the job of editors and of their choice of reviewers and peer reviewers.

Even the worst criminals have the right to expose their point of view. That has to be carefully scrutinized, of course, but it still must be listened and then could be accepted or rejected by the judge an jury, who are responsible for protecting the community from the consequences of accepting false arguments,

What is the duty of the judge in courts is the duty of editors and peer reviewers in the publishing business (with different tools: I am net saying that authors are criminals).
The poor quality of reporting, the unfairness of reviews, the lack of presenting contrasting points of view in current publications is not just the fault of writers:  it is a consequence of the acquiescence of most editors towards the industry (large sponsored trials and reviews from "opinion leaders" do increase the Impact Factor, and large Impact Factors increase publisher's satisfaction) and their batteries of low-quality and sponsored peer reviewers.

Yesterday I was reading the report of a publicly funded (if scientists are biased by money, then public millions should have the same effect of private money, and producers of CT scanners and healthcare organizations also have financial interests), large trial on lung cancer screening just published on the NEJM. This is a very important study with important results, which will be widely read and quoted for years. Still, the lack of proper review and the number of reporting flaws is impressive: their primary outcomes are survival and incidence of cancer, yet they fail to present proper actuarial curves. Cases occurring after missing a screening are combined with those occurring after the screening period (rather than considered as interval cancers), there is no mention of the time when they  started to count cancers as occurring after the screening period rather than interval cancers. They fail to give an estimate of potential overdiagnosis (at least 30% of cancers detected by CT screening, according to my raw computation), just to name a few.
If I would write a letter about it, I would complain more with the reviewers than with the authors.


Therefore, it is my opinion that the editor of the BMJ is simply giving up her duty and responsibility, proposing to refuse to judge what she is supposed to judge.

It is this the main field of the battle, and the only measure that I can propose, in addition to exercising judgment, is to abandon anonymous peer review (would it be any better a football game with an anonymous arbiter?) in favor of open review and to disclose the conflicts of interests of peer reviewers as well as of the authors. But no rule can succeed by itself, unless associated to a strong commitment to improve the quality of the process of peer review of commentaries as well as of original research.

As proposed by Stephen, this approach would have the advantage of non being limited to face commercial conflicts of interests, but also those arising from competition for public funds  or from careers in the health systems, or any other conflict or flaw.


This, and not the "ad hominem" fallacy should be in my opinion editor's response to the problems posed by the conflicts of interest.


regards,
Piersante Sestini

On 11/08/12 14:02, Stephen Senn wrote:
> I am certainly not proposing that we do nothing to improve the reporting of pharma trials. Jeremy is no doubt unaware of the proposal that I made at my inaugural lecture, Figures, Figurers and Pharmaceuticals at University College London in 1997 (which is understandable and forgivable) but which I have made in print elsewhere since,  that data from clinical trials should be made publicly available(1). I also think and have said so in print that the situation on authorship of pharma trials needs to be improved (1,6) but that many academic lab heads should also ask themselves whether their presence on publications is justified.
>
> As regards trusting results, my solution is that everybody (including but not restricted to the pharma industry) should be much more open about sharing data (This is one of the excellent things about Cochrane but it comes with a warning: you should pay careful attention to the data Cochrane provides but you should be critical about the results of any analyses.) This includes being open with patients and healthy volunteers(3,4). Partly under pressure from others, pharma is taking steps in the right direction but academia should not be complacent. I think that many academics are blissfully unaware as to what changes in their own practice will be necessary (2,5,7).
> Stephen
>
> References
> 1. Senn, S. J. (2002), "Authorship of Drug Industry Trials," Pharmaceutical Statistics, 1, 5-7.
> 2. Senn, S. J. (2006), "Sharp Tongues and Bitter Pills," Significance, 3, 123-125.
> 3 Senn. S.J. (1997), "Are Placebo Run Ins Justified?," BRITISH MEDICAL JOURNAL, 314, 1191-1193.
> 4. Working Party on Statistical Issues in First-in-Man Studies. (2007), "Statistical Issues in First-in-Man Studies," Journal of the Royal Statistical Society, Series A, 170, 517-579
> 5.  Senn, S. J. (2002), "Maintaining the Integrity of the Scientific Record. Scientific Standards Observed by Medical Journals Can Still Be Improved," BRITISH MEDICAL JOURNAL, 324, 169.
> 6. Senn, S. J. (2002), "Rules for Publication of Industry-Sponsored Clinical Trials," in Rules for Publication of Industry Sponsored Trials, eds. G. Stock and M. Lessl, Berlin: Ernst Schering Research Foundation.
> 7. Senn, S. J. (2005), "Bitter Pills and Puffed Trials," PLoS Medicine, 2.
>