Letters
Author Affiliations: Center for Medicine and the Media, Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire (Schwartz, Woloshin). Corresponding Author: Lisa M. Schwartz, MD, MS, Center for Medicine and the Media, Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, 35 Centerra Pkwy, Lebanon, NH 03756 ([email protected]). Conflict of Interest Disclosures: Drs Schwartz and Woloshin report that they are cofounders and shareholders of Informulary Inc, a provider of data about the benefits, harms, and uncertainties of prescription drugs. They prepared the drug facts box for Belviq, which is posted online by Consumer Reports (http://www.consumerreports.org/cro/news/2013/06/making-sense-of -belviq-s-weight-loss-claims/index.htm). 1. Council on Science and Public Health. Is obesity a disease? report of the Council on Science and Public Health. CSAPH Report 3-A-13. http://www.ama-assn.org/assets/meeting/2013a/a13-addendum -refcomm-d.pdf. Accessed April 19, 2014. 2. Food and Drug Administration. Belviq approval letter. Application No. 022529Orig1s000. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012 /022529Orig1s000Approv.pdf. Accessed June 14, 2014.
Renda Soylemez Wiener, MD, MPH Christopher G. Slatore, MD, MSc
3. Food and Drug Administration. Qsymia approval letter. http://www .accessdata.fda.gov/drugsatfda_docs/appletter/2012/022580Origs000ltr.pdf. Accessed June 14, 2014.
Author Affiliations: The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts (Wiener); Center for Healthcare Organization & Implementation Research, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts (Wiener); Health Services Research & Development, Portland VA Medical Center, Portland, Oregon (Slatore); Division of Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland (Slatore).
Real-World Evidence About Potential Psychosocial Harms of Lung Cancer Screening
Corresponding Author: Renda Soylemez Wiener, MD, MPH, The Pulmonary Center, Boston University School of Medicine, 72 E Concord St, R-304, Boston, MA 02118 ([email protected]).
To the Editor We applaud Harris and colleagues1 for their clearly organized taxonomy of potential harms associated with lowdose computed tomographic screening for lung cancer, which includes “psychological harms” as 1 of 4 categories. The authors point out that patients undergoing surveillance for a screening-detected indeterminate nodule are exposed to a prolonged state of uncertainty but comment that there is limited evidence about the associated psychological harms. We would like to direct readers to research we have conducted to evaluate the psychological impact on patients undergoing surveillance for an indeterminate pulmonary nodule.2-4 Although the patients in our studies had incidentally detected nodules, we believe the psychological distress many patients described can shed light on how patients may experience surveillance of screen-detected nodules. Indeed, our results are likely more informative of what patients who receive care in real-world settings may experience than studies of patients enrolled in lung cancer screening trials. Sources of distress included fear of cancer (most patients grossly overestimated the likelihood that the nodule was malignant), concerns about the evaluation process (eg, radiation exposure, pain, and physical complications should invasive testing be needed), guilt about tobacco use, and the frustrating uncertainty about what the nodule was and what the workup might entail. Our work demonstrates the potential magnitude and downstream effects of these psychological harms, which affected adherence with care in some cases and which led others to make dramatic lifestyle changes (ie, changing jobs to have more time with family under the assumption the nodule would turn out to be malignant). Most importantly, our work highlights actions clinicians can take to reduce the distress patients experience after a pulmonary nodule is detected. In particular, patient-clinician communication processes must be improved. We suggest several communication strategies endorsed by patients.2,4 These in1416
clude notifying the patient of the finding of a nodule in a conversation rather than by letter; using plain, understandable language that is not dismissive; explaining what the nodule looks like and what it may be; providing an estimate of the likelihood that the nodule is cancer; explaining the plan for workup, including expected duration of surveillance, a rationale for why or why not a biopsy may be needed, and acknowledgment of the potential harms of evaluation; and allowing time to address patients’ questions and concerns. These strategies may help mitigate the distress patients undergoing surveillance of a nodule—whether screen detected or incidentally identified— may experience.
Conflict of Interest Disclosures: None reported. 1. Harris RP, Sheridan SL, Lewis CL, et al. The harms of screening: a proposed taxonomy and application to lung cancer screening. JAMA Intern Med. 2014;174 (2):281-285. 2. Wiener RS, Gould MK, Woloshin S, Schwartz LM, Clark JA. What do you mean, a spot? a qualitative analysis of patients’ reactions to discussions with their physicians about pulmonary nodules. Chest. 2013;143(3):672-677. 3. Wiener RS, Gould MK, Woloshin S, Schwartz LM, Clark JA. “The thing is not knowing”: patients’ perspectives on surveillance of an indeterminate pulmonary nodule [published online December 16, 2012]. Health Expect. doi:10.1111/hex.12036. 4. Slatore CG, Press N, Au DH, Curtis JR, Wiener RS, Ganzini L. What the heck is a “nodule”? a qualitative study of veterans with pulmonary nodules. Ann Am Thorac Soc. 2013;10(4):330-335.
In Reply We thank Wiener and Slatore for their letter and for informing us of their excellent research to examine the psychological harms of detecting indeterminate pulmonary nodules. Although their studies do not deal with screen-detected nodules, we agree that their findings are relevant to similar nodules found on lung cancer screening. And, as we suspected, their findings are sobering. Clearly there are human costs to extended surveillance and prolonged uncertainty. As one of their patients stated so well: “the thing is not knowing.”1 This type of research needs to be conducted more widely, and for more screening situations, to help us better quantify the effects of screening on real people’s lives. We also agree with Wiener and Slatore about the potential benefit of improved communication with patients as a way to reduce psychological harm. However, findings from the breast cancer screening literature suggest that the time for education is before, not after, the screening test.2 Furthermore, several studies have documented that reducing the time between receiving an abnormal mammogram result and the resolution of the finding can reduce distress.3 Finally, the psychological (as well as other) harms of lung cancer screening could also be reduced by screening less in-
JAMA Internal Medicine August 2014 Volume 174, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Birmingham User on 06/09/2015
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Letters
tensively. For example, limiting screening to only a higherrisk group over a shorter period (eg, 3-5 annual screens rather than the recommended 25) could result in nearly the same reduction in lung cancer deaths with fewer harms, including fewer indeterminate nodules.4 Starting a screening program with less-intensive screening, increasing intensity only if indicated by future research, may be a better approach than starting the program with high intensity and then trying to scale screening back if suggested by further evidence.
cannot be mitigated. The harms caused by a false-positive cancer screening test finding can be controlled if the informed patient chooses watchful waiting rather than an immediate invasive biopsy. Women who refuse screening mammography because of pain or the wish to avoid ionizing radiation to their breasts should be informed of these issues and offered screening with MRI.
Russell P. Harris, MD, MPH Stacey L. Sheridan, MD, MPH Carmen L. Lewis, MD, MPH
Corresponding Author: David L. Keller, MD, PO Box 14295, Torrance, CA 90503 ([email protected]). Conflict of Interest Disclosures: None reported.
Author Affiliations: Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill (Harris); Division of General Medicine and Epidemiology, University of North Carolina at Chapel Hill (Sheridan); Division of General Medicine and Clinical Epidemiology, Department of Medicine, University of North Carolina at Chapel Hill (Lewis). Corresponding Author: Russell P. Harris, MD, MPH, Cecil G. Sheps Center for Health Services Research, University of North Carolina, 725 Martin Luther King Blvd, CB7590, Chapel Hill, NC 27599-7590 ([email protected]). Conflict of Interest Disclosures: None reported. 1. Wiener RS, Gould MK, Woloshin S, Schwartz LM, Clark JA. “The thing is not knowing”: patients’ perspectives on surveillance of an indeterminate pulmonary nodule [published online December 16, 2012]. Health Expect. doi:10.1111/hex.12o36. 2. Austoker J, Ong G. Written information needs of women who are recalled for further investigation of breast screening: results of a multicentre study. J Med Screen. 1994;1(4):238-244. 3. Barton MB, Morley DS, Moore S, et al. Decreasing women’s anxieties after abnormal mammograms: a controlled trial. J Natl Cancer Inst. 2004;96(7):529538. 4. Kovalchik SA, Tammemagi M, Berg CD, et al. Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med. 2013;369(3): 245-254.
In Defense of Screening for Breast Cancer With Magnetic Resonance Imaging To the Editor Regarding the recent commentary by Hwang and Bedrosian1: 1. The high prices charged by hospitals for magnetic resonance imaging (MRI) examinations are not intrinsically necessary. The regular cash price for a noncontrast 3 Tesla brain MRI, including all physician and facility charges, is $350 at a local for-profit imaging center.2 The local nonprofit hospitals charge far more for the same examination. 2. Younger women have a higher content of glandular breast tissue, which is sensitive to the ionizing radiation exposure with mammography. They also have more expected years of lifespan during which to develop radiationinduced breast malignant neoplasms. 3. Many women are not compliant with screening mammography because of the pain caused by the compression of the breast glandular tissues. Again, younger women are more affected by this pain and have more quality-adjusted life years to lose by not screening. Breast MRI is not painful. 4. The increased sensitivity of breast MRI, even at the expense of reduced specificity, is compatible with the purpose of a screening examination. When screening for cancer, a false-positive finding can be addressed with further testing, but the harm caused by a false-negative finding often jamainternalmedicine.com
David L. Keller, MD
1. Hwang E, Bedrosian I. Patterns of breast magnetic resonance imaging use: an opportunity for data-driven resource allocation. JAMA Intern Med. 2014;174(1): 122-124. 2. MRI Center of Torrance, CA. http://www.mricenters.com. Accessed November 18, 2013.
In Reply We thank Dr Keller for drawing attention to several additional points regarding the use of breast magnetic resonance imaging (MRI) for breast cancer screening. With respect to the first comment, we concur that the attributes of a screening test include that it must be both noninvasive and inexpensive. While the $350 reported charges for an MRI by a forprofit screening center is not exorbitant, it still remains much higher than the cost of a routine screening mammogram, is a significant out-of-pocket cost for most patients, and begs the question of whether patients should cover the cost of their own cancer screening, given that MRI has not been shown to offer benefit over mammography for the general population. Dr Keller further mentions the limitations of mammography, particularly in younger women. Most breast cancer screening guidelines recommend against mammographic screening in women younger than 40 years owing to the low breast cancer incidence in this population; women in this age group constitute only 6.5% of all newly diagnosed breast cancers.1 Furthermore, it has been clearly demonstrated that premenopausal women experience MRI changes with the menstrual cycle, which can often lead to false-positive MRI findings.2 Thus younger patients are likely to derive the least benefit and possibly greatest harm from the increased sensitivity of MRI screening, resulting in additional workup and unnecessary biopsies. The last and most salient comment refers to the value of breast MRI as a screening test. The National Cancer Institute states that at least 2 requirements must be met for a screening test to be efficacious3: 1. A test or procedure must be available to detect cancers earlier than if the cancer were detected as a result of the development of symptoms. 2. Evidence must be available that treatment initiated earlier as a consequence of screening results in an improved outcome. Both mammography and MRI likely fulfill these criteria. However, of more practical relevance are the questions: “what is the likelihood of disease in the setting of a positive test result?” (positive predictive value [PPV]) and “what is the likelihood of no disease in the setting of a negative test?” (negative predictive value [NPV]). Importantly, both PPV and NPV are JAMA Internal Medicine August 2014 Volume 174, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Birmingham User on 06/09/2015
1417
Author Affiliations: Center for Medicine and the Media, Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire (Schwartz, Woloshin). Corresponding Author: Lisa M. Schwartz, MD, MS, Center for Medicine and the Media, Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, 35 Centerra Pkwy, Lebanon, NH 03756 ([email protected]). Conflict of Interest Disclosures: Drs Schwartz and Woloshin report that they are cofounders and shareholders of Informulary Inc, a provider of data about the benefits, harms, and uncertainties of prescription drugs. They prepared the drug facts box for Belviq, which is posted online by Consumer Reports (http://www.consumerreports.org/cro/news/2013/06/making-sense-of -belviq-s-weight-loss-claims/index.htm). 1. Council on Science and Public Health. Is obesity a disease? report of the Council on Science and Public Health. CSAPH Report 3-A-13. http://www.ama-assn.org/assets/meeting/2013a/a13-addendum -refcomm-d.pdf. Accessed April 19, 2014. 2. Food and Drug Administration. Belviq approval letter. Application No. 022529Orig1s000. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012 /022529Orig1s000Approv.pdf. Accessed June 14, 2014.
Renda Soylemez Wiener, MD, MPH Christopher G. Slatore, MD, MSc
3. Food and Drug Administration. Qsymia approval letter. http://www .accessdata.fda.gov/drugsatfda_docs/appletter/2012/022580Origs000ltr.pdf. Accessed June 14, 2014.
Author Affiliations: The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts (Wiener); Center for Healthcare Organization & Implementation Research, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts (Wiener); Health Services Research & Development, Portland VA Medical Center, Portland, Oregon (Slatore); Division of Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland (Slatore).
Real-World Evidence About Potential Psychosocial Harms of Lung Cancer Screening
Corresponding Author: Renda Soylemez Wiener, MD, MPH, The Pulmonary Center, Boston University School of Medicine, 72 E Concord St, R-304, Boston, MA 02118 ([email protected]).
To the Editor We applaud Harris and colleagues1 for their clearly organized taxonomy of potential harms associated with lowdose computed tomographic screening for lung cancer, which includes “psychological harms” as 1 of 4 categories. The authors point out that patients undergoing surveillance for a screening-detected indeterminate nodule are exposed to a prolonged state of uncertainty but comment that there is limited evidence about the associated psychological harms. We would like to direct readers to research we have conducted to evaluate the psychological impact on patients undergoing surveillance for an indeterminate pulmonary nodule.2-4 Although the patients in our studies had incidentally detected nodules, we believe the psychological distress many patients described can shed light on how patients may experience surveillance of screen-detected nodules. Indeed, our results are likely more informative of what patients who receive care in real-world settings may experience than studies of patients enrolled in lung cancer screening trials. Sources of distress included fear of cancer (most patients grossly overestimated the likelihood that the nodule was malignant), concerns about the evaluation process (eg, radiation exposure, pain, and physical complications should invasive testing be needed), guilt about tobacco use, and the frustrating uncertainty about what the nodule was and what the workup might entail. Our work demonstrates the potential magnitude and downstream effects of these psychological harms, which affected adherence with care in some cases and which led others to make dramatic lifestyle changes (ie, changing jobs to have more time with family under the assumption the nodule would turn out to be malignant). Most importantly, our work highlights actions clinicians can take to reduce the distress patients experience after a pulmonary nodule is detected. In particular, patient-clinician communication processes must be improved. We suggest several communication strategies endorsed by patients.2,4 These in1416
clude notifying the patient of the finding of a nodule in a conversation rather than by letter; using plain, understandable language that is not dismissive; explaining what the nodule looks like and what it may be; providing an estimate of the likelihood that the nodule is cancer; explaining the plan for workup, including expected duration of surveillance, a rationale for why or why not a biopsy may be needed, and acknowledgment of the potential harms of evaluation; and allowing time to address patients’ questions and concerns. These strategies may help mitigate the distress patients undergoing surveillance of a nodule—whether screen detected or incidentally identified— may experience.
Conflict of Interest Disclosures: None reported. 1. Harris RP, Sheridan SL, Lewis CL, et al. The harms of screening: a proposed taxonomy and application to lung cancer screening. JAMA Intern Med. 2014;174 (2):281-285. 2. Wiener RS, Gould MK, Woloshin S, Schwartz LM, Clark JA. What do you mean, a spot? a qualitative analysis of patients’ reactions to discussions with their physicians about pulmonary nodules. Chest. 2013;143(3):672-677. 3. Wiener RS, Gould MK, Woloshin S, Schwartz LM, Clark JA. “The thing is not knowing”: patients’ perspectives on surveillance of an indeterminate pulmonary nodule [published online December 16, 2012]. Health Expect. doi:10.1111/hex.12036. 4. Slatore CG, Press N, Au DH, Curtis JR, Wiener RS, Ganzini L. What the heck is a “nodule”? a qualitative study of veterans with pulmonary nodules. Ann Am Thorac Soc. 2013;10(4):330-335.
In Reply We thank Wiener and Slatore for their letter and for informing us of their excellent research to examine the psychological harms of detecting indeterminate pulmonary nodules. Although their studies do not deal with screen-detected nodules, we agree that their findings are relevant to similar nodules found on lung cancer screening. And, as we suspected, their findings are sobering. Clearly there are human costs to extended surveillance and prolonged uncertainty. As one of their patients stated so well: “the thing is not knowing.”1 This type of research needs to be conducted more widely, and for more screening situations, to help us better quantify the effects of screening on real people’s lives. We also agree with Wiener and Slatore about the potential benefit of improved communication with patients as a way to reduce psychological harm. However, findings from the breast cancer screening literature suggest that the time for education is before, not after, the screening test.2 Furthermore, several studies have documented that reducing the time between receiving an abnormal mammogram result and the resolution of the finding can reduce distress.3 Finally, the psychological (as well as other) harms of lung cancer screening could also be reduced by screening less in-
JAMA Internal Medicine August 2014 Volume 174, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Birmingham User on 06/09/2015
jamainternalmedicine.com
Letters
tensively. For example, limiting screening to only a higherrisk group over a shorter period (eg, 3-5 annual screens rather than the recommended 25) could result in nearly the same reduction in lung cancer deaths with fewer harms, including fewer indeterminate nodules.4 Starting a screening program with less-intensive screening, increasing intensity only if indicated by future research, may be a better approach than starting the program with high intensity and then trying to scale screening back if suggested by further evidence.
cannot be mitigated. The harms caused by a false-positive cancer screening test finding can be controlled if the informed patient chooses watchful waiting rather than an immediate invasive biopsy. Women who refuse screening mammography because of pain or the wish to avoid ionizing radiation to their breasts should be informed of these issues and offered screening with MRI.
Russell P. Harris, MD, MPH Stacey L. Sheridan, MD, MPH Carmen L. Lewis, MD, MPH
Corresponding Author: David L. Keller, MD, PO Box 14295, Torrance, CA 90503 ([email protected]). Conflict of Interest Disclosures: None reported.
Author Affiliations: Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill (Harris); Division of General Medicine and Epidemiology, University of North Carolina at Chapel Hill (Sheridan); Division of General Medicine and Clinical Epidemiology, Department of Medicine, University of North Carolina at Chapel Hill (Lewis). Corresponding Author: Russell P. Harris, MD, MPH, Cecil G. Sheps Center for Health Services Research, University of North Carolina, 725 Martin Luther King Blvd, CB7590, Chapel Hill, NC 27599-7590 ([email protected]). Conflict of Interest Disclosures: None reported. 1. Wiener RS, Gould MK, Woloshin S, Schwartz LM, Clark JA. “The thing is not knowing”: patients’ perspectives on surveillance of an indeterminate pulmonary nodule [published online December 16, 2012]. Health Expect. doi:10.1111/hex.12o36. 2. Austoker J, Ong G. Written information needs of women who are recalled for further investigation of breast screening: results of a multicentre study. J Med Screen. 1994;1(4):238-244. 3. Barton MB, Morley DS, Moore S, et al. Decreasing women’s anxieties after abnormal mammograms: a controlled trial. J Natl Cancer Inst. 2004;96(7):529538. 4. Kovalchik SA, Tammemagi M, Berg CD, et al. Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med. 2013;369(3): 245-254.
In Defense of Screening for Breast Cancer With Magnetic Resonance Imaging To the Editor Regarding the recent commentary by Hwang and Bedrosian1: 1. The high prices charged by hospitals for magnetic resonance imaging (MRI) examinations are not intrinsically necessary. The regular cash price for a noncontrast 3 Tesla brain MRI, including all physician and facility charges, is $350 at a local for-profit imaging center.2 The local nonprofit hospitals charge far more for the same examination. 2. Younger women have a higher content of glandular breast tissue, which is sensitive to the ionizing radiation exposure with mammography. They also have more expected years of lifespan during which to develop radiationinduced breast malignant neoplasms. 3. Many women are not compliant with screening mammography because of the pain caused by the compression of the breast glandular tissues. Again, younger women are more affected by this pain and have more quality-adjusted life years to lose by not screening. Breast MRI is not painful. 4. The increased sensitivity of breast MRI, even at the expense of reduced specificity, is compatible with the purpose of a screening examination. When screening for cancer, a false-positive finding can be addressed with further testing, but the harm caused by a false-negative finding often jamainternalmedicine.com
David L. Keller, MD
1. Hwang E, Bedrosian I. Patterns of breast magnetic resonance imaging use: an opportunity for data-driven resource allocation. JAMA Intern Med. 2014;174(1): 122-124. 2. MRI Center of Torrance, CA. http://www.mricenters.com. Accessed November 18, 2013.
In Reply We thank Dr Keller for drawing attention to several additional points regarding the use of breast magnetic resonance imaging (MRI) for breast cancer screening. With respect to the first comment, we concur that the attributes of a screening test include that it must be both noninvasive and inexpensive. While the $350 reported charges for an MRI by a forprofit screening center is not exorbitant, it still remains much higher than the cost of a routine screening mammogram, is a significant out-of-pocket cost for most patients, and begs the question of whether patients should cover the cost of their own cancer screening, given that MRI has not been shown to offer benefit over mammography for the general population. Dr Keller further mentions the limitations of mammography, particularly in younger women. Most breast cancer screening guidelines recommend against mammographic screening in women younger than 40 years owing to the low breast cancer incidence in this population; women in this age group constitute only 6.5% of all newly diagnosed breast cancers.1 Furthermore, it has been clearly demonstrated that premenopausal women experience MRI changes with the menstrual cycle, which can often lead to false-positive MRI findings.2 Thus younger patients are likely to derive the least benefit and possibly greatest harm from the increased sensitivity of MRI screening, resulting in additional workup and unnecessary biopsies. The last and most salient comment refers to the value of breast MRI as a screening test. The National Cancer Institute states that at least 2 requirements must be met for a screening test to be efficacious3: 1. A test or procedure must be available to detect cancers earlier than if the cancer were detected as a result of the development of symptoms. 2. Evidence must be available that treatment initiated earlier as a consequence of screening results in an improved outcome. Both mammography and MRI likely fulfill these criteria. However, of more practical relevance are the questions: “what is the likelihood of disease in the setting of a positive test result?” (positive predictive value [PPV]) and “what is the likelihood of no disease in the setting of a negative test?” (negative predictive value [NPV]). Importantly, both PPV and NPV are JAMA Internal Medicine August 2014 Volume 174, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Birmingham User on 06/09/2015
1417
