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Displaying 1-10 letters out of 2262 published
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The USPSTF Recommendations Are Not Scientifically Based - Underestimate the Benefit of Mammography and Admit That Lives Will Be Lost Unnecessarily
Submit responseThe US Preventive Services Task Force (USPSTF) acknowledges that mammography screening, beginning at the age of 40, significantly decreases breast cancer deaths. Their guidelines, however, ignore the science and direct measurements of benefit to limit access to screening.
1. None of the parameters of screening change abruptly at the age of 50 or any other age (1). The age of 50 is an arbitrary threshold. 2. The USPSTF correctly used the randomized, controlled trials (RCT) as scientific proof of benefit. However, since the RCT did not stratify by risk, there is no proof that screening based on risk will save lives, and no scientific support for recommending screening based on risk (2). Screening only women at high risk will miss the 75-90% of breast cancers that occur in women who are not at high risk. 3. The USPSTF chose the lowest possible reduction in breast cancer deaths (15%), unaware of the fact that the RCT underestimate benefit. Women allocated to be screened who refuse the invitation, and die of breast cancer, are still counted as having been screened (non-compliance). Women allocated to be controls whose lives are saved by mammograms that they obtain outside the trial, are still counted as unscreened controls (contamination). 4. The USPSTF recognizes a 30 % decrease in breast cancer deaths in the U.S. since 1990 but ignore it, and ignore the 40% decrease in breast cancer deaths reported in Sweden (3), predominantly due to screening, that applies to women in their forties. 5 Ignoring direct data they used a 15% reduction in deaths and estimated 1300 women needed to be screened (NTS) to save one life was a reasonable number to support recommending mammography. They would deny screening to women ages 40-49 because they estimated their NTS was 1900. In reality there is 30-40% decrease in deaths for women in their forties so, using their formula, the NTS is 950-705 for women in their forties putting them well below the threshold. 6 Most false positive mammograms are easily resolved with a few extra pictures. Most biopsies are needle biopsies. Over treatment is not the fault of mammography and should be addressed to the oncologists. 7. The Task Force admits that lives will be lost by increasing the time between screens to two years.
Before denying women access to screening, anyone advising women needs to be aware of the facts.
References
1. Kopans DB. Informed decision making: age of 50 is arbitrary and has no demonstrated influence on breast cancer screening in women. Am J Roentgenology 2005;185:177-82
2. Kopans DB. Screening mammography for women age 40 to 49 years. Ann Intern Med. 2007;147:740-1.
3. Swedish Organised Service Screening Evaluation Group. Reduction in breast cancer mortality from organized service screening with mammography: 1. Further confirmation with extended data. Cancer Epidemiol Biomarkers Prev. 2006;15:45-51.
Conflict of Interest:
None declared
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Overdiagnosis with breast screening was seriously underestimated
Submit responseNelson et al. calculate the reduction in breast cancer mortality based on the randomised trials (1), but for the most important harm, overdiagnosis, they present no calculations. They quote a mixture of observational studies and results from statistical models with unverifiable and doubtful assumptions. Only for the Malmo trial do they quote real data, but these data were obtained 15 years after the trial ended, when many additional cancers had occurred in both arms of the trial. When we corrected for this dilution, and for the fact that 24% of the women in the control group were also screened during the trial, we found 25% overdiagnosis (2), rather than the 10% reported by the authors.
It is indefensible that Nelson et al. base their estimate of overdiagnosis on flawed studies when there are data from about 600,000 randomised women, which we pooled in our Cochrane systematic review in 2009 (3), and before that in 2006 and 2001. We found 31% more lumpectomies and mastectomies. In July, we reported 52% overdiagnosis in a systematic review of publicly organised mammography screening programmes, without using assumptions or statistical modelling (4). It is also curious that Nelson et al. do not quote our Cochrane review, as they searched the Cochrane Library.
Nelson et al. reported that most studies found between 1% and 10% overdiagnosis. However, systematic reviewing is not a consensus conference, it is a scientific discipline, and Nelson et al. overlook that the small estimates of overdiagnosis are based on poor science, mostly produced by researchers with vested interests in screening. If one opens one's eyes, unaided by any statistical tricks, one cannot escape seeing a huge amount of overdiagnosis, e.g. in the UK (4,5).
The U.S. Preventive Services Task Force now recommends against breast screening in women aged 40-49 years, but it may be the case for all age groups that the harms outweigh the benefits. An effect of 15% and an overdiagnosis of 30% mean that for every 2000 women invited for screening throughout 10 years, one will have her life prolonged and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily (3). Furthermore, in USA about 1000 women will have experienced a false positive diagnosis (3). The psychological strain until one knows whether or not it was cancer can be severe. The harms caused by overdiagnosis are life-long.
References
1. Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for Breast Cancer: An Update for the U.S. Preventive Services Task Force. Ann Intern Med 2009; 151: 727-37.
2. Gotzsche PC, Jorgensen KJ. Estimate of harm/benefit ratio of mammography screening was five times too optimistic. http://bmj.bmjjournals.com/cgi/eletters/332/7543/691, 2006.
3. Gotzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2009;(4):CD001877.
4. Jorgensen KJ, Gotzsche PC. Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends. BMJ 2009; 339: b2587.
5. Jorgensen KJ, Gotzsche PC. It is time for a new paradigm for overdiagnosis with screening mammography. http://www.bmj.com/cgi/eletters/339/jul09_1/b2587 - 218754, 2009.
Conflict of Interest:
None declared
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Comment to Editorial: Cost-Effectiveness of Biologics as First-Line Treatment of Rheumatoid Arthritis (Ann Intern Med 2009 151:668-669)
Submit responseDr Maarten Boers writes elegantly about our cost-effectiveness study. We appreciate his ideas but some require comment(1). He feels, "curiously, the investigators shy away from a firm conclusion, instead stating that the cost-effectiveness of early biologics is still uncertain." We feel that the case cannot be closed for at least three major reasons: 1. The long-term impact of very early initiation of aggressive antirheumatic therapy, and biologic therapy, in particular, is largely unknown. These include the long-term impact on mortality, the need for joint replacement and the rate of disability decades after the initiation of these therapeutic strategies. 2. Other parameters profoundly impact the cost-effectiveness ratio of these therapeutic strategies, the major ones being the availability of effective alternatives after failure of several biologics, the price of these agents, the induction of long-term drug-free remission and the ability to identify responders to biologics before treatment initiation. Because of these uncertainties, a firm conclusion is not justified. Rather, our findings support the use of aggressive DMARDs before biologics in very early RA from a cost-effectiveness perspective. The study identifies the key parameters that are uncertain and drive the results, and which should be studied to improve future decisions.
We calibrated estimates of the published literature against real patients from the National Data Bank for Rheumatic Diseases (NDB). Such calibration techniques are appropriate and commonly applied in cost- effectiveness studies. Calibration in an another unrelated data set would further validate the model. However, at present, significant circularity is unlikely given that the patient populations used to derive most of the parameters and those used to calibrate the model are largely different.
Finally, Dr Boers takes issue with the model and its treatment of glucocorticoids and feels that including them in only the NSAID strategy arm is "medically inappropriate." Glucocorticoids are effective and clinically useful. In the doses originally used for rheumatoid arthritis, the benefits were outweighed by serious and sometimes fatal long-term effects, increased susceptibility to infection, osteoporosis, obesity, hypertension, or glucose intolerance. The long-term risk/benefit ratio of lower doses is debated(2), and in North America, more likely to be used to put out "fires" rather than long-term. Adding steroids to the DMARD strategy would, as Dr Boers points out, likely to be a conservative bias with respect to the findings(3).
REFERENCES
1. Finckh A, Bansback N, Marra CA, Anis AH, Michaud K, Lubin S, et al. Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost- effectiveness analysis. Ann Intern Med 2009;151(9):612-21.
2. Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Ines LB, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 2006;65(3):285-93.
3. Maillefert JF. Appropriate and inappropriate use of oral glucocorticoid therapy in rheumatoid arthritis. Joint Bone Spine 2006;73(3):234-5.
Conflict of Interest:
None declared
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Vaccination Against Pandemic Influenza (H1N1): Adjuvant does matter
Submit responseIn their study Khazeni et al. chose to examine an adjuvanted vaccine as a conservative estimate in light of potentially increased vaccine side effects and costs with an adjuvant (1). They assumed that severe pandemic (H1N1) vaccine side effects could occur in 1 in 100000 vaccinated individuals (2). They state that they examined vaccine efficacy consistent with nonadjuvanted pandemic (H1N1) trial results (3), so the decision to use nonadjuvanted vaccine would not affect their conclusions other than decreasing costs, as they described in sensitivity analysis. We believe that the question of adjuvanted versus nonadjuvanted vaccine pandemic (H1N1) is rather important. Not only concerning the issues that were addressed by Khazeni et al, but also concerning the acceptability of the vaccination among the population. In this respect, Germany currently experiences a dramatic public discussion. This is driven by the fact that the federal and state health departments ordered adjuvanted vaccine for the general population whereas some governmental employees and politicians receive nonadjuvanted vaccine. As a result, not only the public opinion but also the opinion of healthcare workers seems to be biased. In a survey supported by the state health department, the statuary accident insurance and the state chamber of physicians (4), it was found that only 29,9% of physicians providing outpatient medical care want to receive adjuvanted A/H1N1 vaccination. This low acceptability points to the importance of the emotional public safety discussion, even in healthcare professionals such as physicians. We thereofore believe that information politics should be improved.
References
1. Khazeni N, Hutton DW, Garber AM, Hupert N, Owens DK. Effectiveness and Cost-Effectiveness of Vaccination Against Pandemic Influenza (H1N1) 2009. Ann Intern Med. 2009 Oct 5. [Epub ahead of print]
2. Neustadt RE, Fineberg HV. The Swine Flu Affair: Decision Making on a Slippery Disease. Washington, DC: National Academies Press Online; 1978.
3. Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, et al. Response after one dose of a monovalent influenza A (H1N1) 2009 vaccine - preliminary report. N Engl J Med. 2009. [PMID: 19745216]
4. Berlin State Chamber of Physicians: http://www.aerztekammer- berlin.de/40presse/15_meldungen/00659_FOBI_Neue_Grippe/index.htm (last update: 2009-11-19)
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The Editors' Response
Submit response"In response to media reports that imply otherwise, Annals of Internal Medicine did not schedule the publication of the US Preventive Services Task Force recommendations about breast cancer screening to coincide with a particular date or event. The background papers (which underwent several rounds of revision over about 5 months based on independent peer review comments and Annals' statistical editor's comments) and the recommendation statement were all in final, accepted form by September 10, 2009. Annals scheduled them to appear in the next available print issue, which was the November 17th issue. Our routine print production process takes about 2 months from final acceptance to print." The Editors
Conflict of Interest:
None declared
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The Editors' Response
Submit response"In response to media reports that imply otherwise, Annals of Internal Medicine did not schedule the publication of the US Preventive Services Task Force recommendations about breast cancer screening to coincide with a particular date or event. The background papers (which underwent several rounds of revision over about 5 months based on independent peer review comments and Annals' statistical editor's comments) and the recommendation statement were all in final, accepted form by September 10, 2009. Annals scheduled them to appear in the next available print issue, which was the November 17th issue. Our routine print production process takes about 2 months from final acceptance to print." The Editors
Conflict of Interest:
None declared
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The Editors' Response
Submit response"In response to media reports that imply otherwise, Annals of Internal Medicine did not schedule the publication of the US Preventive Services Task Force recommendations about breast cancer screening to coincide with a particular date or event. The background papers (which underwent several rounds of revision over about 5 months based on independentpeer review comments and Annals' statistical editor's comments) and the recommendation statement were all in final, accepted form by September 10, 2009. Annals scheduled them to appear in the next available print issue, which was the November 17th issue. Our routine print production process takes about 2 months from final acceptance to print." The Editors
Conflict of Interest:
None declared
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Re:The 40-50 age group.
Submit responseThe U.S. Preventive Services Task Force (USPSTF) recently recommended against routine mammographic screening in women ages 40-49 (1). The recommendation was based on the relative probability of unscreened women dying of breast cancer and the reduction in mortality provided by mammographic screening. Based on these studies the USPSTF issued a blanket recommended against routine screening mammography in all women 40-49 years -of-age (1).
Lacking from the USPSTF study is evidence to support a reduction in mammography screening in African American and Latino women who are less than 50 years-of-age (1). The USPSTF study analyzed the risk/benefit mammography as a function of a woman's age but did not consider the potential contributions of race and ethnicity (1). Investigators did not state the racial and ethnic composition of study participants and there was no analysis of the risk/benefit of mammography in African-American and Latino women (1).
It is concerning that USPSTF issued a one-size-fits-all blanket breast cancer screening recommendation without considering whether the recommendation is appropriate for all women.
Our current recommendations for mammographic screening are based on studies in European, European-Canadian and European-American women. Eight reported randomized trials studied mammography's effectiveness in the United States, Sweden, Canada, and the United Kingdom (for a review, see reference 2). These studies balance the relative contributions of mammographic density (sensitivity and specificity of mammography) and the death rate from breast cancers (2). To our knowledge, there has been no large-scale analysis of the effectiveness of mammographic screening in African-American and Latino women.
Studies of mammographic screening in women ages 40-49 are complex because younger women have a lower incidence of breast cancer, denser breast tissue (which can lower sensitivity), and, on average, faster growing, biologically aggressive cancers. Relative to European-American women, African-American women have lower breast density, faster growing cancers, and a higher likelihood of dying from breast cancer (3-5). Since the death rate from breast cancer in African-American women is higher and mammographic density is typically lower, it is likely that the benefit from mammographic screening will be higher in African-American, and perhaps Latino women, than in European-American women.
So where's the evidence to recommend against routine mammography screening of African American and Latino women under 50 years-of-age?
We agree with the USPSTF that there is a need for change. But the change we call for is an end to one-size-fits-all recommendations and inclusion of African-American and Latino women in clinical trials testing the benefit of mammographic screening.
References:
(1) Mandelblatt, J.S. et al. Effects of Mammography Screening Under Different Screening Schedules: Model Estimates of Potential Benefits and Harms (2009) Annals of Internal Medicine 151: 738-745
(2) Elmore, J.E., et al. Screening for Breast Cancer. (2005) JAMA 293:1245-1256.
(3) Stuedal, A., et al. Does Breast Size Modify the Association between Mammographic Density and Breast Cancer Risk? (2008) Cancer Epidemiol Biomarkers Prev 17:621-627.
(4) Ursin, G., et al. Mammographic Density and Breast Cancer in Three Ethnic Groups (2003) Cancer Epidemiol Biomarkers Prev 12:332-339..
(5) Elledge, R.M., et al. Tumor Biologic Factors and Breast Cancer Prognosis Among White, Hispanic, and Black Women in the United States (1994) JNCI 86:705-712.
Conflict of Interest:
None declared
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Re:The 40-50 age group.
Submit responseThis is one problem with what we do on a daily basis. Evidence has to be separated from the intuitive reactions we have. The response from the radiologist implies that he knows that all of the tumors he finds will have an impact on the life of the patient.
Conflict of Interest:
None declared
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The 40-50 age group.
Submit responseAs lead mammographer in my hospital, I can tell you that if we stop screening 40-50 yr. olds we will experience a giant step backward in detecting early cancer. Many of the cases that are detected at in situ or stage 1 will be seen later in her life as Stage 3 or 4 ; not much prevention there. I am sure women are much smarter than that. Shame on giving in on Government health care ideas.
Conflict of Interest:
None declared