Letters
of encouraging it.2 A critical mass of informed citizens will not resolve all health care problems but can constitute a major triggering factor for better care. Informed patients will ask questions that require physicians to become better informed, who in turn will more easily see through biased reporting and attempts to create undue hopes and fears. In the 19th century, people’s health improved from a combination of clean water, better hygiene, and sufficient amounts of food. The 20th century saw the professionalization of medicine and scientific breakthroughs, but it has left us with uninformed physicians and patients. In the 21st century, we need a third revolution to promote clean information and better physicians.
Schwartz1 is in contrast to another recent article on drug treatment of obesity, which noted that the new drugs may be useful adjuncts to lifestyle treatment for carefully selected patients.4 Bias against people with obesity, even from physicians, is well documented.5 Patients with obesity have difficulty finding clinicians who take their condition seriously enough to offer compassionate, evidence-based treatment.
Odette Wegwarth, PhD Gerd Gigerenzer, PhD
Corresponding Author: Theodore K. Kyle, RPh, MBA, Office of the Chairman, Obesity Action Coalition, 2270 Country Club Dr, Pittsburgh, PA 15241 (ted.kyle @conscienhealth.org).
Author Affiliations: Max Planck Institute for Human Development, Harding Center for Risk Literacy, Berlin, Germany (Wegwarth, Gigerenzer). Corresponding Author: Odette Wegwarth, PhD, Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany ([email protected]). Conflict of Interest Disclosures: None reported. 1. Gigerenzer G, Mata J, Frank R. Public knowledge of benefits of breast and prostate cancer screening in Europe. J Natl Cancer Inst. 2009;101(17):1216-1220. 2. Gigerenzer G, Gray JAM. Launching the century of the patient. In: Gigerenzer G, Gray JAM, eds. Better Doctors, Better Patients, Better Decisions: Envisioning Healthcare 2020: Strüngmann Forum Report. Vol 6. Cambridge, MA: MIT Press; 2011:1-19. 3. Wegwarth O, Schwartz LM, Woloshin S, Gaissmaier W, Gigerenzer G. Do physicians understand cancer screening statistics? a national survey of primary care physicians in the United States. Ann Intern Med. 2012;156(5):340-349. 4. Bond M. Decision-making: risk school. Nature. 2009;461(7268): 1189-1192.
Theodore K. Kyle, RPh, MBA Joseph Nadglowski Jr, BS Author Affiliations: Obesity Action Coalition, Tampa, Florida (Kyle, Nadglowski).
Conflict of Interest Disclosures: Mr Kyle is an unpaid board member and chairman of the Obesity Action Coalition. Mr Nadglowski is an employee of the Obesity Action Coalition, a 501C3 organization that receives financial support from Vivus Inc, which markets phentermine-topiramate (Qysmia), and Eisai Inc, which markets lorcaserin hydrochloride (Belviq). 1. Woloshin S, Schwartz LM. The new weight-loss drugs, lorcaserin and phentermine-topiramate: slim pickings? JAMA Intern Med. 2014;174(4):615-619. 2. Expert Panel on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (US). Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1998. 3. American Medical Association. Resolution 420 (A-13): recognition of obesity as a disease. Proceedings of the House of Delegates 162nd Annual Meeting, June 15-19, 2013. http://www.ama-assn.org/assets/meeting/2013a /a13-addendum-refcomm-d.pdf. Accessed February 14, 2014. 4. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311(1):74-86. 5. Puhl RM, Heuer CA. The stigma of obesity: a review and update. Obesity (Silver Spring). 2009;17(5):941-964.
Drug Treatment of Obesity To the Editor We object to the explicit trivialization of obesity by Woloshin and Schwartz1 in their article on the weight-loss medications, lorcaserin hydrochloride and phentermine topiramate. The authors' assertion that “obesity is not an emergency—it is not even a disease”1(p618) is incorrect and of concern to millions of people whose health and quality of life are greatly diminished by this chronic disease. In 1998, an expert panel convened by the National Institutes of Health stated that “obesity is a chronic disease, and both the patient and the practitioner need to understand that successful treatment requires a life-long effort.” 2(p1) Subsequently, many other organizations—including The Obesity Society, the American Association of Clinical Endocrinologists, and most recently, the American Medical Association 3 —have all affirmed that obesity is indeed a chronic disease. Yet Woloshin and Schwartz1 use their opinion that obesity is not a disease as justification for taking issue with the Food and Drug Administration’s decision to approve 2 new treatments and to dismiss their benefits as unimportant. The goal of nonsurgical treatment of obesity is to achieve and maintain a 5% to 10% loss of body weight, which has been shown to yield important improvements in health and quality of life.3 The dismissive tone of the article by Woloshin and 1414
To the Editor The Obesity Society, of which I am the president, is concerned with Woloshin and Schwartz’s dismissal of obesity as a disease, disregard for the well-established benefits of modest weight loss, and focus on cardiovascular risk as the sole reason to treat obesity.1 The authors declare, “…obesity is not an emergency, it is not even a disease.”1(p618) Many diseases are not emergencies yet still warrant medical intervention. In fact, the American Medical Association recently joined The Obesity Society, the American Association for Clinical Endocrinologists, the World Health Organization, the National Institutes of Health, and the Food and Drug Administration (FDA), among many others, in classifying obesity as a disease.2 The authors also characterize 5% weight loss as an insufficient benefit. Yet, science clearly demonstrates that this magnitude of weight loss improves diabetes, physical functioning, pain, and quality of life.3 A singular focus on using obesity drugs to reduce cardiovascular events misses the numerous important benefits of treating obesity on overall health. Moreover, Woloshin and Schwartz 1 exaggerate the potential adverse effects of lorcaserin hydrochloride and phentermine-topiramate, suggesting an underlying bias in their argument: that any risk (even potential) is unac-
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Letters
ceptable. Further, the authors describe one of the medications as “toxic” and the other as causing heart valve regurgitation.1 To the contrary, the FDA accepted the phase 3 safety data as evidence for the absence of an effect on valvular heart disease. Selective 5-HT2c drugs like lorcaserin affect only those receptors, and not serotonin receptors, mediating the valvular cardiac effect (5-HT2b).4 The FDA, based on the recommendation of an expert advisory panel, has adopted an approach that permits approval for obesity drugs based on reasonable confidence of general and cardiovascular safety while conducting definitive outcomes trials to assess cardiovascular events.5 The FDA has taken this position to address the lack of treatment options for patients with obesity. In addition, the authors’ focus on mean weight loss ignores the reality that not every patient with obesity will respond to every obesity medication. Recognizing this, the FDA provides guidance for stopping these drug therapies when no benefit is likely.5 As is with any medication, a healthy conversations between physicians and patients supports informed choices made through close consideration of the risks and benefits of obesity pharmacotherapy. Opinion that strays from scientific data may keep those affected by obesity from seeking, and accessing, the medications they need. Steven R. Smith, MD Author Affiliations: President, The Obesity Society; Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford-Burnham Medical Research Institute, Orlando. Corresponding Author: Steven R. Smith, MD, Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford-Burnham Clinical Research Institute, 301 Princeton St, Orlando, FL 32804 (steven.r.smith.md @flhosp.org). Conflict of Interest Disclosures: Dr Smith holds stock in Jenrin Discovery and Zafgen; has research grants from Amylin Pharmaceuticals, Eli Lilly and Company, and Takeda; serves on advisory boards for Amylin Pharmaceuticals and Takeda; and is a consultant for Amylin Pharmaceuticals, Arena Pharmaceuticals Inc, AstraZeneca, Boehringer Ingelheim Pharma GmbH & Co KG, BristolMeyersSquibb, Eisai Inc, Elcelyx, Eli Lilly and Company, Five Prime Therapeutics Inc, GSK US Processing/Genpact AP, NGM Pharma, Novo Nordisk A/S, Orexigen Theralpeutics Inc, Piramal Life Sciences, Takeda Global Research and Development Inc, and Zafgen. 1. Woloshin S, Schwartz LM. The new weight-loss drugs, lorcaserin and phentermine-topiramate: slim pickings? JAMA Intern Med. 2014;174(4): 615-619. 2. American Medical Association. Resolution 420 (A-13): recognition of obesity as a disease. Proceedings of the House of Delegates 162nd Annual Meeting, June 15-19, 2013. http://www.ama-assn.org/assets/meeting/2013a /a13-addendum-refcomm-d.pdf. June 19, 2013. Accessed February 14, 2014. 3. AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society [published online November 12, 2013]. Obesity (Silver Spring). doi:10.1002/oby.20660. 4. Meltzer HY, Roth BL. Lorcaserin and pimavanserin: emerging selectivity of serotonin receptor subtype-targeted drugs. J Clin Invest. 2013;123(12):4986-4991. 5. Food and Drug Administration Center for Drug Evaluation and Research. Summary Minutes of the Endocrinologic and Metabolic Drugs Advisory Committee Meeting. http://www.fda.gov/downloads /AdvisoryCommittees/CommitteesMeetingMaterials/Drugs /EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM303352.pdf. March 2012. Accessed February 14, 2014. jamainternalmedicine.com
In Reply The Obesity Society and the Obesity Action Coalition are mistaken. Our article was motivated by genuine concern for the health of people living with obesity, regardless of how it is classified. Although it is true that the American Medical Association now calls obesity a disease, the association did so against the advice of its own Council on Science and Public Health. The council stated “opinions within the medical profession have been divided for a number of years on whether obesity should be considered a disease, rather than a condition or disease risk factor.”1(p2) We a g re e w it h t h e c o u n c i l’s c o n c l u s i o n t h at “ it i s unclear that recognizing obesity as a disease, as opposed to a ‘condition’ or ‘disorder’ will result in improved health outcomes.”1(p6) Our goal was not to debate diagnostic labels, however, but to review the benefits, harms, and uncertainties of the new weight-loss drugs lorcaserin hydrochloride (Belviq) and phentermine-topiramate (Qysmia). This evidence from the phase 3 trials that the Food and Drug Administration (FDA) relied on to approve the drugs will help people who are obese make their own informed decisions. One fact to highlight is that both drugs were approved on the basis of a surrogate outcome, weight loss. A 5% loss of weight has been associated with improvements in some patient outcomes; it is not known, however, whether these drugs improve morbidity or mortality. On average, patients taking phentermine-topiramate can expect a 7% weight loss, but those taking lorcaserin can only expect a 3% weight loss. Smith claims we exaggerated the potential adverse effects of the drugs. In fact, we simply quoted what the FDA said in the approval letters: “there have been signals of a serious risk of major adverse cardiovascular events with some medications developed for the treatment of obesity, and available data have not definitively excluded the potential for this serious risk with [lorcaserin hydrochloride or phentermine and topiramate extended release].”2,3 With regard to possible cardiac valvulopathy, the lorcaserin studies did not meet the FDA’s criteria for excluding a 50% increase in risk. In fact, the FDA was sufficiently concerned about potential cardiovascular adverse effects that it required postmarketing cardiovascular outcome studies for both drugs. Unfortunately, the studies appear to be 8 to 16 months behind schedule. Recruitment for the lorcaserin study has only just begun, and the phenterminetopiramate study has not even been registered yet. Even if the studies are completed on time, results are not due until 2018.2,3 Eisai Inc and Vivus Inc, the manufacturers of the weight-loss drugs, provide financial support to The Obesity Society and the Obesity Action Coalition. The society and the coalition should advocate with the companies for the completion of these postmarketing studies as soon as possible. In the meantime, physicians and patients should approach these drugs cautiously. Lisa M. Schwartz, MD, MS Steven Woloshin, MD, MS JAMA Internal Medicine August 2014 Volume 174, Number 8
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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-
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of encouraging it.2 A critical mass of informed citizens will not resolve all health care problems but can constitute a major triggering factor for better care. Informed patients will ask questions that require physicians to become better informed, who in turn will more easily see through biased reporting and attempts to create undue hopes and fears. In the 19th century, people’s health improved from a combination of clean water, better hygiene, and sufficient amounts of food. The 20th century saw the professionalization of medicine and scientific breakthroughs, but it has left us with uninformed physicians and patients. In the 21st century, we need a third revolution to promote clean information and better physicians.
Schwartz1 is in contrast to another recent article on drug treatment of obesity, which noted that the new drugs may be useful adjuncts to lifestyle treatment for carefully selected patients.4 Bias against people with obesity, even from physicians, is well documented.5 Patients with obesity have difficulty finding clinicians who take their condition seriously enough to offer compassionate, evidence-based treatment.
Odette Wegwarth, PhD Gerd Gigerenzer, PhD
Corresponding Author: Theodore K. Kyle, RPh, MBA, Office of the Chairman, Obesity Action Coalition, 2270 Country Club Dr, Pittsburgh, PA 15241 (ted.kyle @conscienhealth.org).
Author Affiliations: Max Planck Institute for Human Development, Harding Center for Risk Literacy, Berlin, Germany (Wegwarth, Gigerenzer). Corresponding Author: Odette Wegwarth, PhD, Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany ([email protected]). Conflict of Interest Disclosures: None reported. 1. Gigerenzer G, Mata J, Frank R. Public knowledge of benefits of breast and prostate cancer screening in Europe. J Natl Cancer Inst. 2009;101(17):1216-1220. 2. Gigerenzer G, Gray JAM. Launching the century of the patient. In: Gigerenzer G, Gray JAM, eds. Better Doctors, Better Patients, Better Decisions: Envisioning Healthcare 2020: Strüngmann Forum Report. Vol 6. Cambridge, MA: MIT Press; 2011:1-19. 3. Wegwarth O, Schwartz LM, Woloshin S, Gaissmaier W, Gigerenzer G. Do physicians understand cancer screening statistics? a national survey of primary care physicians in the United States. Ann Intern Med. 2012;156(5):340-349. 4. Bond M. Decision-making: risk school. Nature. 2009;461(7268): 1189-1192.
Theodore K. Kyle, RPh, MBA Joseph Nadglowski Jr, BS Author Affiliations: Obesity Action Coalition, Tampa, Florida (Kyle, Nadglowski).
Conflict of Interest Disclosures: Mr Kyle is an unpaid board member and chairman of the Obesity Action Coalition. Mr Nadglowski is an employee of the Obesity Action Coalition, a 501C3 organization that receives financial support from Vivus Inc, which markets phentermine-topiramate (Qysmia), and Eisai Inc, which markets lorcaserin hydrochloride (Belviq). 1. Woloshin S, Schwartz LM. The new weight-loss drugs, lorcaserin and phentermine-topiramate: slim pickings? JAMA Intern Med. 2014;174(4):615-619. 2. Expert Panel on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (US). Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1998. 3. American Medical Association. Resolution 420 (A-13): recognition of obesity as a disease. Proceedings of the House of Delegates 162nd Annual Meeting, June 15-19, 2013. http://www.ama-assn.org/assets/meeting/2013a /a13-addendum-refcomm-d.pdf. Accessed February 14, 2014. 4. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311(1):74-86. 5. Puhl RM, Heuer CA. The stigma of obesity: a review and update. Obesity (Silver Spring). 2009;17(5):941-964.
Drug Treatment of Obesity To the Editor We object to the explicit trivialization of obesity by Woloshin and Schwartz1 in their article on the weight-loss medications, lorcaserin hydrochloride and phentermine topiramate. The authors' assertion that “obesity is not an emergency—it is not even a disease”1(p618) is incorrect and of concern to millions of people whose health and quality of life are greatly diminished by this chronic disease. In 1998, an expert panel convened by the National Institutes of Health stated that “obesity is a chronic disease, and both the patient and the practitioner need to understand that successful treatment requires a life-long effort.” 2(p1) Subsequently, many other organizations—including The Obesity Society, the American Association of Clinical Endocrinologists, and most recently, the American Medical Association 3 —have all affirmed that obesity is indeed a chronic disease. Yet Woloshin and Schwartz1 use their opinion that obesity is not a disease as justification for taking issue with the Food and Drug Administration’s decision to approve 2 new treatments and to dismiss their benefits as unimportant. The goal of nonsurgical treatment of obesity is to achieve and maintain a 5% to 10% loss of body weight, which has been shown to yield important improvements in health and quality of life.3 The dismissive tone of the article by Woloshin and 1414
To the Editor The Obesity Society, of which I am the president, is concerned with Woloshin and Schwartz’s dismissal of obesity as a disease, disregard for the well-established benefits of modest weight loss, and focus on cardiovascular risk as the sole reason to treat obesity.1 The authors declare, “…obesity is not an emergency, it is not even a disease.”1(p618) Many diseases are not emergencies yet still warrant medical intervention. In fact, the American Medical Association recently joined The Obesity Society, the American Association for Clinical Endocrinologists, the World Health Organization, the National Institutes of Health, and the Food and Drug Administration (FDA), among many others, in classifying obesity as a disease.2 The authors also characterize 5% weight loss as an insufficient benefit. Yet, science clearly demonstrates that this magnitude of weight loss improves diabetes, physical functioning, pain, and quality of life.3 A singular focus on using obesity drugs to reduce cardiovascular events misses the numerous important benefits of treating obesity on overall health. Moreover, Woloshin and Schwartz 1 exaggerate the potential adverse effects of lorcaserin hydrochloride and phentermine-topiramate, suggesting an underlying bias in their argument: that any risk (even potential) is unac-
JAMA Internal Medicine August 2014 Volume 174, Number 8
Copyright 2014 American Medical Association. All rights reserved.
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Letters
ceptable. Further, the authors describe one of the medications as “toxic” and the other as causing heart valve regurgitation.1 To the contrary, the FDA accepted the phase 3 safety data as evidence for the absence of an effect on valvular heart disease. Selective 5-HT2c drugs like lorcaserin affect only those receptors, and not serotonin receptors, mediating the valvular cardiac effect (5-HT2b).4 The FDA, based on the recommendation of an expert advisory panel, has adopted an approach that permits approval for obesity drugs based on reasonable confidence of general and cardiovascular safety while conducting definitive outcomes trials to assess cardiovascular events.5 The FDA has taken this position to address the lack of treatment options for patients with obesity. In addition, the authors’ focus on mean weight loss ignores the reality that not every patient with obesity will respond to every obesity medication. Recognizing this, the FDA provides guidance for stopping these drug therapies when no benefit is likely.5 As is with any medication, a healthy conversations between physicians and patients supports informed choices made through close consideration of the risks and benefits of obesity pharmacotherapy. Opinion that strays from scientific data may keep those affected by obesity from seeking, and accessing, the medications they need. Steven R. Smith, MD Author Affiliations: President, The Obesity Society; Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford-Burnham Medical Research Institute, Orlando. Corresponding Author: Steven R. Smith, MD, Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford-Burnham Clinical Research Institute, 301 Princeton St, Orlando, FL 32804 (steven.r.smith.md @flhosp.org). Conflict of Interest Disclosures: Dr Smith holds stock in Jenrin Discovery and Zafgen; has research grants from Amylin Pharmaceuticals, Eli Lilly and Company, and Takeda; serves on advisory boards for Amylin Pharmaceuticals and Takeda; and is a consultant for Amylin Pharmaceuticals, Arena Pharmaceuticals Inc, AstraZeneca, Boehringer Ingelheim Pharma GmbH & Co KG, BristolMeyersSquibb, Eisai Inc, Elcelyx, Eli Lilly and Company, Five Prime Therapeutics Inc, GSK US Processing/Genpact AP, NGM Pharma, Novo Nordisk A/S, Orexigen Theralpeutics Inc, Piramal Life Sciences, Takeda Global Research and Development Inc, and Zafgen. 1. Woloshin S, Schwartz LM. The new weight-loss drugs, lorcaserin and phentermine-topiramate: slim pickings? JAMA Intern Med. 2014;174(4): 615-619. 2. American Medical Association. Resolution 420 (A-13): recognition of obesity as a disease. Proceedings of the House of Delegates 162nd Annual Meeting, June 15-19, 2013. http://www.ama-assn.org/assets/meeting/2013a /a13-addendum-refcomm-d.pdf. June 19, 2013. Accessed February 14, 2014. 3. AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society [published online November 12, 2013]. Obesity (Silver Spring). doi:10.1002/oby.20660. 4. Meltzer HY, Roth BL. Lorcaserin and pimavanserin: emerging selectivity of serotonin receptor subtype-targeted drugs. J Clin Invest. 2013;123(12):4986-4991. 5. Food and Drug Administration Center for Drug Evaluation and Research. Summary Minutes of the Endocrinologic and Metabolic Drugs Advisory Committee Meeting. http://www.fda.gov/downloads /AdvisoryCommittees/CommitteesMeetingMaterials/Drugs /EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM303352.pdf. March 2012. Accessed February 14, 2014. jamainternalmedicine.com
In Reply The Obesity Society and the Obesity Action Coalition are mistaken. Our article was motivated by genuine concern for the health of people living with obesity, regardless of how it is classified. Although it is true that the American Medical Association now calls obesity a disease, the association did so against the advice of its own Council on Science and Public Health. The council stated “opinions within the medical profession have been divided for a number of years on whether obesity should be considered a disease, rather than a condition or disease risk factor.”1(p2) We a g re e w it h t h e c o u n c i l’s c o n c l u s i o n t h at “ it i s unclear that recognizing obesity as a disease, as opposed to a ‘condition’ or ‘disorder’ will result in improved health outcomes.”1(p6) Our goal was not to debate diagnostic labels, however, but to review the benefits, harms, and uncertainties of the new weight-loss drugs lorcaserin hydrochloride (Belviq) and phentermine-topiramate (Qysmia). This evidence from the phase 3 trials that the Food and Drug Administration (FDA) relied on to approve the drugs will help people who are obese make their own informed decisions. One fact to highlight is that both drugs were approved on the basis of a surrogate outcome, weight loss. A 5% loss of weight has been associated with improvements in some patient outcomes; it is not known, however, whether these drugs improve morbidity or mortality. On average, patients taking phentermine-topiramate can expect a 7% weight loss, but those taking lorcaserin can only expect a 3% weight loss. Smith claims we exaggerated the potential adverse effects of the drugs. In fact, we simply quoted what the FDA said in the approval letters: “there have been signals of a serious risk of major adverse cardiovascular events with some medications developed for the treatment of obesity, and available data have not definitively excluded the potential for this serious risk with [lorcaserin hydrochloride or phentermine and topiramate extended release].”2,3 With regard to possible cardiac valvulopathy, the lorcaserin studies did not meet the FDA’s criteria for excluding a 50% increase in risk. In fact, the FDA was sufficiently concerned about potential cardiovascular adverse effects that it required postmarketing cardiovascular outcome studies for both drugs. Unfortunately, the studies appear to be 8 to 16 months behind schedule. Recruitment for the lorcaserin study has only just begun, and the phenterminetopiramate study has not even been registered yet. Even if the studies are completed on time, results are not due until 2018.2,3 Eisai Inc and Vivus Inc, the manufacturers of the weight-loss drugs, provide financial support to The Obesity Society and the Obesity Action Coalition. The society and the coalition should advocate with the companies for the completion of these postmarketing studies as soon as possible. In the meantime, physicians and patients should approach these drugs cautiously. Lisa M. Schwartz, MD, MS Steven Woloshin, MD, MS JAMA Internal Medicine August 2014 Volume 174, Number 8
Copyright 2014 American Medical Association. All rights reserved.
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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
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