Re: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial
PART 2:
Levman keeps dismissing population-based studies, as they are, allegedly, inferior (or "misleading") to the findings of randomized controlled trials. Yet, the Cochrane group reported that out of the eight large prospective randomized mammogram trials half of them are seriously flawed, while only three trials are adequately randomized none of which showing a statistically significant breast cancer mortality benefit [13]. If you take the commonly unacknowledged flaws in the pro-mammogram studies into consideration you'll end up with very little, if any, robust evidence, as far as randomized controlled trials concern, in favor of a mammography benefit [9,13].
Levman explained that randomized controlled trials are "the strongest source" of scientific evidence [1]. A much more important and fundamental principle affects any methodological source of evidence, beyond the strength of source of evidence. That is, a good "tool", such as a randomized controlled trial, is only of meaningful service and reliance if it is utilized properly.
For instance, the HIP trial was shown to be severely flawed and biased [13]. The Swedish Two-County trial has also many serious flaws: the assessment of cause of death by the trial authors was not blinded [23], another investigation of the data of one of the counties found only a 10% decrease in mortality (compared to 24% as claimed by Tabar, et al.) [24], and a number of breast cancers and deaths were not accounted for [25]. Evidently, "confounding factors", leading to misleading unreliable conclusions, are quite abound in large pro-mammogram randomized trials [13].
Highly touted by the leadership of the mammography community, these two aforecited large randomized trials were very influential in the induction of organized screening programs around the world. Where were the pro-mammogram voices who are swift and eager to "find fault" in anti-mammogram research but remained silent and inert about these seriously flawed randomized trials? Why, instead, do they keep citing them as relevant pro-mammography evidence? If a good tool had been used improperly, is the result of its use still relevant simply because the tool has the name "randomized controlled trial" stamped on it?
Levman's prime reliance on the value of randomized controlled trials would suggest he would heavily focus on statistically significant findings thereof, as it is the principal overriding factor of the method to form strong conclusions from. But oddly, in his response [1], after commenting on a subunit of data of the current Miller et al. study [16] regarding the prevalence screening issue, showing no statistical significance, Levman also goes on to cite "the UK Age trial" [11] in which no statistical significance was reached in terms of breast cancer mortality reduction as if these data were embodied with great scientific relevance. Does Levman inadvertently assign an undeserved status of specious significance to statistically insignificant pro-mammogram findings within fundamentally anti-mammogram randomized controlled trials? Is the resort to potential random findings of failed randomized controlled mammogram trials superior to findings of rigorous population-based studies?
Contrary to Levman's statement "the alternative population based studies that do not control the mammographic screening status of each subject are a much less reliable source on which to base conclusions", Gøtzsche explained why the old randomized mammogram trials are inadequate and unreliable to reveal the effect of screening and why, therefore, population-based studies become most relevant to present times [9].
Ask yourself, should you ignore or casually dismiss a plethora of relevant population-based studies from many nations, such as Norway, the US, the UK, the Netherlands, Australia, Italy, Sweden, Switzerland, Belgium, Denmark, that show either no noteworthy reduction in breast cancer mortality from systematic screening with mammography or no significant change in incidence of invasive advanced breast cancers after 10-15+ years of widespread screening in favor of a few large prospective randomized controlled trials some of which are seriously flawed and the most reliable of the bunch found no statistically significant decrease in mortality from breast cancer?
To get a clear(er) picture of a situation, arguably, the overall evidence needs to be taken into consideration, rather than relying on a very small set of large randomized controlled trials, very few of which are scientifically reliable. And, if one recognizes and acknowledges the significant impact of vested interests in a lot of pro-mammogram research [9,26], the medical industry's unscientific notions on the progression of breast cancer, the neglect or dismissal of the data on total mortality, collateral damages, and the vast extent of overdiagnosis in the evaluation of the benefit of mammography, if one does not neglect to earnestly consider the various research data from numerous meaningful population studies on the lack of a notable benefit on mortality and the incidence of advanced malignant breast cancer, or the data from many nations showing that breast cancer mortality had declined years prior to the general introduction of organized mammographic screening programs or that the reduction in breast cancer mortality in non-screened ages declined much more than in screen ages [27], the overall evidence for the pro-screening value of mammography resembles much more a piece of Swiss cheese rather than a block of solid concrete.
One can hope that the public recognizes the importance and necessity to scrutinize mammography on many of these, oftentimes disregarded albeit pertinent, issues to gain a more complete and more realistic view of the status of this procedure.
References
1. Levman J, "Re: Accusations of Bias Versus Actual Bias Regarding Mammography", British Medical Journal, 348:g366, 7-April-2014.
2. Hefti R, "Accusations of Bias Versus Actual Bias Regarding Mammography", British Medical Journal, 348:g366, March 31, 2014.
3. Gøtzsche PC, "Relation between breast cancer mortality and screening effectiveness: systematic review of the mammography trials", Dan Med Bull. 2011 Mar;58(3):A4246.
4. Gøtzsche PC, Jørgensen KJ, Zahl PH, Mæhlen J, "Why mammography screening has not lived up to expectations from the randomised trials", Cancer Causes Control. 2012 Jan;23(1):15-21.
5. Bleyer A, Welch HG, "Effect of three decades of screening mammography on breast-cancer incidence", N Engl J Med. 2012 Nov 22;367(21):1998-2005. doi: 10.1056/NEJMoa1206809.
6. Gøtzsche PC, Olsen O, “Is screening for breast cancer with mammography justifiable”, Lancet. 2000 Jan 8;355(9198):129-34.
7. Gøtzsche PC, “Commentary: Medicalisation of risk factors”, BMJ. 2002 April 13; 324(7342): 886–891.
8. Gøtzsche PC, “Time to stop mammography screening”, CMAJ. 2011 Nov 22;183(17):1957-8.
9. Gøtzsche PC, "Benefit and harms of mammography screening, and invitations to screening, Written statement for the UK hearing on mammography screening, 8 March 2012", 2012 Feb 27. http://www.cochrane.dk/screening/Statement for UK Panel.pdf.
10. Gøtzsche PC, “Mammography Screening: Truth, Lies and Controversy”, 2012
11. Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L; Trial Management Group, "Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial", Lancet. 2006 Dec 9;368(9552):2053-60.
12. Andersson I, Aspegren K, Janzon L, Landberg T, Lindholm K, Linell F, Ljungberg O, Ranstam J, Sigfússon B, "Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial", BMJ. 1988 Oct 15;297(6654):943-8.
13. Gøtzsche PC, Nielsen M, "Screening for breast cancer with mammography", Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001877. doi: 10.1002/14651858.CD001877.pub3.
14. Gøtzsche PC, Jørgensen KJ, "Screening for breast cancer with mammography", Cochrane Database Syst Rev. 2013 Jun 4;6:CD001877. doi: 10.1002/14651858.CD001877.pub5.
15. Brodersen J, Jørgensen KJ, Gøtzsche PC, “The benefits and harms of screening for cancer with a focus on breast screening.”, Pol Arch Med Wewn. 2010 Mar;120(3):89-94.
16. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA, "Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial", BMJ. 2014 Feb 11;348:g366. doi: 10.1136/bmj.g366.
17. Lynge E, "Mammography screening for breast cancer in Copenhagen April 1991-March 1997. Mammography Screening Evaluation Group", APMIS Suppl. 1998;83:1-44.
18. Welch HG, “Should I Be Tested for Cancer?: Maybe Not and Here's Why”, 2006
19. Zahl PH, Maehlen J, Welch HG, “The Natural History of Invasive Breast Cancers Detected by Screening Mammography”, Arch Intern Med., Vol. 168, No. 21, Pg. 2311-2316, 2008
20. Baum M, "Harms from breast cancer screening outweigh benefits if death caused by treatment is included", BMJ. 2013 Jan 23;346:f385. doi: 10.1136/bmj.f385.
21. Early Breast Cancer Trialists' Collaborative Group, “Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials”, Lancet. 2000 May 20;355(9217):1757-70.
22. Early Breast Cancer Trialists' Collaborative Group, “Radiotherapy for early breast cancer”, Cochrane Database Syst Rev. 2002;(2):CD003647.
23. Gøtzsche PC, Nielsen M, "Screening for breast cancer with mammography", Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001877.
24. Nyström L, Andersson I, Bjurstam N, Frisell J, Nordenskjöld B, Rutqvist LE, “Long-term effects of mammography screening: updated overview of the Swedish randomised trials”, Lancet. 2002 Mar 16;359(9310):909-19.
25. Zahl PH, Gøtzsche PC, Andersen JM, Mæhlen J., “Results of the Two-County trial of mammography screening are not compatible with contemporaneous official Swedish breast cancer statistics.”, Dan Med Bull. 2006 Nov;53(4):438-40.
26. Jørgensen KJ, Klahn A, Gøtzsche PC, “Are benefits and harms in mammography screening given equal attention in scientific articles? A cross-sectional study”, BMC Med. 2007 May 30;5:12.
27. Autier P, Boniol M, Gavin A, Vatten LJ, “Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database”, BMJ. 2011 Jul 28;343:d4411. doi: 10.1136/bmj.d4411.
Competing interests:
Author of the (e)book "The Mammogram Myth" (2013)
Rapid Response:
Re: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial
PART 2:
Levman keeps dismissing population-based studies, as they are, allegedly, inferior (or "misleading") to the findings of randomized controlled trials. Yet, the Cochrane group reported that out of the eight large prospective randomized mammogram trials half of them are seriously flawed, while only three trials are adequately randomized none of which showing a statistically significant breast cancer mortality benefit [13]. If you take the commonly unacknowledged flaws in the pro-mammogram studies into consideration you'll end up with very little, if any, robust evidence, as far as randomized controlled trials concern, in favor of a mammography benefit [9,13].
Levman explained that randomized controlled trials are "the strongest source" of scientific evidence [1]. A much more important and fundamental principle affects any methodological source of evidence, beyond the strength of source of evidence. That is, a good "tool", such as a randomized controlled trial, is only of meaningful service and reliance if it is utilized properly.
For instance, the HIP trial was shown to be severely flawed and biased [13]. The Swedish Two-County trial has also many serious flaws: the assessment of cause of death by the trial authors was not blinded [23], another investigation of the data of one of the counties found only a 10% decrease in mortality (compared to 24% as claimed by Tabar, et al.) [24], and a number of breast cancers and deaths were not accounted for [25]. Evidently, "confounding factors", leading to misleading unreliable conclusions, are quite abound in large pro-mammogram randomized trials [13].
Highly touted by the leadership of the mammography community, these two aforecited large randomized trials were very influential in the induction of organized screening programs around the world. Where were the pro-mammogram voices who are swift and eager to "find fault" in anti-mammogram research but remained silent and inert about these seriously flawed randomized trials? Why, instead, do they keep citing them as relevant pro-mammography evidence? If a good tool had been used improperly, is the result of its use still relevant simply because the tool has the name "randomized controlled trial" stamped on it?
Levman's prime reliance on the value of randomized controlled trials would suggest he would heavily focus on statistically significant findings thereof, as it is the principal overriding factor of the method to form strong conclusions from. But oddly, in his response [1], after commenting on a subunit of data of the current Miller et al. study [16] regarding the prevalence screening issue, showing no statistical significance, Levman also goes on to cite "the UK Age trial" [11] in which no statistical significance was reached in terms of breast cancer mortality reduction as if these data were embodied with great scientific relevance. Does Levman inadvertently assign an undeserved status of specious significance to statistically insignificant pro-mammogram findings within fundamentally anti-mammogram randomized controlled trials? Is the resort to potential random findings of failed randomized controlled mammogram trials superior to findings of rigorous population-based studies?
Contrary to Levman's statement "the alternative population based studies that do not control the mammographic screening status of each subject are a much less reliable source on which to base conclusions", Gøtzsche explained why the old randomized mammogram trials are inadequate and unreliable to reveal the effect of screening and why, therefore, population-based studies become most relevant to present times [9].
Ask yourself, should you ignore or casually dismiss a plethora of relevant population-based studies from many nations, such as Norway, the US, the UK, the Netherlands, Australia, Italy, Sweden, Switzerland, Belgium, Denmark, that show either no noteworthy reduction in breast cancer mortality from systematic screening with mammography or no significant change in incidence of invasive advanced breast cancers after 10-15+ years of widespread screening in favor of a few large prospective randomized controlled trials some of which are seriously flawed and the most reliable of the bunch found no statistically significant decrease in mortality from breast cancer?
To get a clear(er) picture of a situation, arguably, the overall evidence needs to be taken into consideration, rather than relying on a very small set of large randomized controlled trials, very few of which are scientifically reliable. And, if one recognizes and acknowledges the significant impact of vested interests in a lot of pro-mammogram research [9,26], the medical industry's unscientific notions on the progression of breast cancer, the neglect or dismissal of the data on total mortality, collateral damages, and the vast extent of overdiagnosis in the evaluation of the benefit of mammography, if one does not neglect to earnestly consider the various research data from numerous meaningful population studies on the lack of a notable benefit on mortality and the incidence of advanced malignant breast cancer, or the data from many nations showing that breast cancer mortality had declined years prior to the general introduction of organized mammographic screening programs or that the reduction in breast cancer mortality in non-screened ages declined much more than in screen ages [27], the overall evidence for the pro-screening value of mammography resembles much more a piece of Swiss cheese rather than a block of solid concrete.
One can hope that the public recognizes the importance and necessity to scrutinize mammography on many of these, oftentimes disregarded albeit pertinent, issues to gain a more complete and more realistic view of the status of this procedure.
References
1. Levman J, "Re: Accusations of Bias Versus Actual Bias Regarding Mammography", British Medical Journal, 348:g366, 7-April-2014.
2. Hefti R, "Accusations of Bias Versus Actual Bias Regarding Mammography", British Medical Journal, 348:g366, March 31, 2014.
3. Gøtzsche PC, "Relation between breast cancer mortality and screening effectiveness: systematic review of the mammography trials", Dan Med Bull. 2011 Mar;58(3):A4246.
4. Gøtzsche PC, Jørgensen KJ, Zahl PH, Mæhlen J, "Why mammography screening has not lived up to expectations from the randomised trials", Cancer Causes Control. 2012 Jan;23(1):15-21.
5. Bleyer A, Welch HG, "Effect of three decades of screening mammography on breast-cancer incidence", N Engl J Med. 2012 Nov 22;367(21):1998-2005. doi: 10.1056/NEJMoa1206809.
6. Gøtzsche PC, Olsen O, “Is screening for breast cancer with mammography justifiable”, Lancet. 2000 Jan 8;355(9198):129-34.
7. Gøtzsche PC, “Commentary: Medicalisation of risk factors”, BMJ. 2002 April 13; 324(7342): 886–891.
8. Gøtzsche PC, “Time to stop mammography screening”, CMAJ. 2011 Nov 22;183(17):1957-8.
9. Gøtzsche PC, "Benefit and harms of mammography screening, and invitations to screening, Written statement for the UK hearing on mammography screening, 8 March 2012", 2012 Feb 27. http://www.cochrane.dk/screening/Statement for UK Panel.pdf.
10. Gøtzsche PC, “Mammography Screening: Truth, Lies and Controversy”, 2012
11. Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L; Trial Management Group, "Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial", Lancet. 2006 Dec 9;368(9552):2053-60.
12. Andersson I, Aspegren K, Janzon L, Landberg T, Lindholm K, Linell F, Ljungberg O, Ranstam J, Sigfússon B, "Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial", BMJ. 1988 Oct 15;297(6654):943-8.
13. Gøtzsche PC, Nielsen M, "Screening for breast cancer with mammography", Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001877. doi: 10.1002/14651858.CD001877.pub3.
14. Gøtzsche PC, Jørgensen KJ, "Screening for breast cancer with mammography", Cochrane Database Syst Rev. 2013 Jun 4;6:CD001877. doi: 10.1002/14651858.CD001877.pub5.
15. Brodersen J, Jørgensen KJ, Gøtzsche PC, “The benefits and harms of screening for cancer with a focus on breast screening.”, Pol Arch Med Wewn. 2010 Mar;120(3):89-94.
16. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA, "Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial", BMJ. 2014 Feb 11;348:g366. doi: 10.1136/bmj.g366.
17. Lynge E, "Mammography screening for breast cancer in Copenhagen April 1991-March 1997. Mammography Screening Evaluation Group", APMIS Suppl. 1998;83:1-44.
18. Welch HG, “Should I Be Tested for Cancer?: Maybe Not and Here's Why”, 2006
19. Zahl PH, Maehlen J, Welch HG, “The Natural History of Invasive Breast Cancers Detected by Screening Mammography”, Arch Intern Med., Vol. 168, No. 21, Pg. 2311-2316, 2008
20. Baum M, "Harms from breast cancer screening outweigh benefits if death caused by treatment is included", BMJ. 2013 Jan 23;346:f385. doi: 10.1136/bmj.f385.
21. Early Breast Cancer Trialists' Collaborative Group, “Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials”, Lancet. 2000 May 20;355(9217):1757-70.
22. Early Breast Cancer Trialists' Collaborative Group, “Radiotherapy for early breast cancer”, Cochrane Database Syst Rev. 2002;(2):CD003647.
23. Gøtzsche PC, Nielsen M, "Screening for breast cancer with mammography", Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001877.
24. Nyström L, Andersson I, Bjurstam N, Frisell J, Nordenskjöld B, Rutqvist LE, “Long-term effects of mammography screening: updated overview of the Swedish randomised trials”, Lancet. 2002 Mar 16;359(9310):909-19.
25. Zahl PH, Gøtzsche PC, Andersen JM, Mæhlen J., “Results of the Two-County trial of mammography screening are not compatible with contemporaneous official Swedish breast cancer statistics.”, Dan Med Bull. 2006 Nov;53(4):438-40.
26. Jørgensen KJ, Klahn A, Gøtzsche PC, “Are benefits and harms in mammography screening given equal attention in scientific articles? A cross-sectional study”, BMC Med. 2007 May 30;5:12.
27. Autier P, Boniol M, Gavin A, Vatten LJ, “Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database”, BMJ. 2011 Jul 28;343:d4411. doi: 10.1136/bmj.d4411.
Competing interests: Author of the (e)book "The Mammogram Myth" (2013)