Letters

peting outcomes than the healthy RCT populations. As we noted in our article,1 no single observational study can be considered definitive, and we cannot exclude unmeasured confounding. Neither can we, however, continue to assume that the treatment benefits and harms seen in RCTs of healthy populations generalize to less healthy clinical populations. The inappropriateness of this extrapolation is increasingly apparent.4 In our article,1 we highlighted the need for RCTs in representative samples of older adults, preferably with risk stratification to detect net benefits and harms in relevant subgroups. Alternatively, real-time clinical registries may shed further light on harms and benefits in key subgroups. The adverse effects of serious fall injuries such as fractures and head injuries on survival and function are comparable to cardiovascular events. The onus, therefore, is on those recommending treatment to show evidence of benefit and lack of harm in the populations for whom they recommend treatment. This is particularly true because, as Fried et al5 found, older persons’ willingness to take medication for prevention of cardiovascular disease is less related to potential benefits than to potential adverse effects. Mary E. Tinetti, MD Ling Han, MD, PhD Gail J. McAvay, PhD Author Affiliations: Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. Corresponding Author: Mary E. Tinetti, MD, Yale School of Medicine, Internal Medicine, 333 Cedar St, PO Box 208025, New Haven, CT, 06520-8025 (mary [email protected]). Conflict of Interest Disclosures: None reported. 1. Tinetti ME, Han L, Lee DS, et al. Antihypertensive medications and serious fall injuries in a nationally representative sample of older adults. JAMA Intern Med. 2014;174(4):588-595. 2. Peters R, Beckett N, Burch L, et al. The effect of treatment based on a diuretic (indapamide) +/- ACE inhibitor (perindopril) on fractures in the Hypertension in the Very Elderly Trial (HYVET). Age Ageing. 2010;39(5):609-616. 3. Tinetti ME, Han L, McAvay GJ, et al. Anti-hypertensive medications and cardiovascular events in older adults with multiple chronic conditions. PLoS One. 2014;9(3):e90733. doi:10.1371/journal.pone.0090733. 4. O’Hare AM, Hotchkiss JR, Kurella Tamura M, et al. Interpreting treatment effects from clinical trials in the context of real-world risk information: end-stage renal disease prevention in older adults. JAMA Intern Med. 2014;174 (3):391-397. 5. Fried TR, Tinetti ME, Towle V, O’Leary JR, Iannone L. Effects of benefits and harms on older persons’ willingness to take medication for primary cardiovascular prevention. Arch Intern Med. 2011;171(10):923-928.

New EMA Policy—Further Measures Needed to Support Comparative Effectiveness Assessments To the Editor We agree with Dr Steinbrook1(p373) that implementation of the new policy of the European Medicines Agency (EMA) on the proactive release of clinical trial data means that “a new era of clinical trial data as a public good will begin.” However, the policy has a major flaw: it will not apply to drugs approved before the effective date.2 A previous transparency initiative, the Food and Drug Administration Amendments Act of 2007, also has the same problem.3 Thus, despite the recent EMA initiative, although comprehensive information will be available on newer drugs in the future, published informa1874

tion on established drugs (ie, approved before the effective date of the policy) will still remain biased, even though they will account for the lion’s share of drugs prescribed in clinical practice for years to come. This imbalance will hamper a meaningful comparison of established and newer drugs and therefore devaluate comparative effectiveness research (especially when indirect comparisons are required). In addition, open questions on established drugs will never be answered. This is particularly relevant for drugs with a large public health impact such as Tamiflu (oseltamivir phosphate; Genentech): it took independent researchers several years to obtain all of the relevant clinical trial data. With the technical possibilities regulatory agencies offer, it would be easy to fill the existing evidence gap and post clinical study reports of all established drugs (or drugs that were never approved) in a central repository. Pharmaceutical companies could also release further reports never submitted to regulatory agencies, thus underlining their commitment to transparency. Unfortunately, EMA’s move towards transparency is again open for discussion. After public consultation on a promising draft policy in 2013,1 in May 2014, EMA—in a step widely criticized as a U-turn—suggested a revised version of the policy, which restricted access to clinical study reports to a view-onscreen-only mode, allowed for redaction of study methods and results, and included restrictive terms of use.4,5 Even after EMA withdrew some of the restrictions on data access, the Agency’s management board was unable to reach a resolution. Further debate and possible adoption of the policy are now planned for October 2014. The initiative by EMA could represent a major breakthrough for transparency in clinical research. However, even after implementation, in many cases independent researchers will still have insufficient information to produce a complete and unbiased comparative effectiveness assessment of a drug. In the interest of patient care, we should make sure we do not give up our pursuit of transparency before reaching the goal line. Beate Wieseler, PhD Natalie McGauran Thomas Kaiser, MD Author Affiliations: Institute for Quality and Efficiency in Health Care, Cologne, Germany. Corresponding Author: Beate Wieseler, PhD, Head of Drug Assessment Department, Institute for Quality and Efficiency in Health Care, Im Mediapark 8, 50670 Cologne, Germany ([email protected]) Conflict of Interest Disclosures: All authors are employees of Institute for Quality and Efficiency in Health Care. In order to produce unbiased health technology assessment reports, the institute depends on access to all of the relevant data on the topic under investigation. The authors therefore support public access to clinical study reports submitted to regulatory authorities. 1. Steinbrook R. The European Medicines Agency and the brave new world of access to clinical trial data. JAMA Intern Med. 2013;173(5):373-374. 2. European Medicines Agency. Draft Policy 70: publication and access to clinical-trial data. 2013. http://www.ema.europa.eu/ema/index.jsp?curl=pages %2Fincludes%2Fdocument%2Fdocument_detail.jsp%3FwebContentId %3DWC500144730&mid=WC0b01ac058009a3dc. Accessed September 22, 2014.

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3. Turner EH. Closing a loophole in the FDA Amendments Act. Science. 2008; 322(5898):44-46. 4. Goldacre B, Godlee F, Heneghan C, et al. Open letter: European Medicines Agency should remove barriers to access clinical trial data. BMJ. 2014;348:g3768. 5. Wieseler B, McGauran N, Kaiser T. EMA’s transparency policy: a placebo intervention? [electronic response to Torjesen I. European drug agency backtracks on plan to give researchers access to clinical trial reports]. BMJ. 2014. http://www.bmj.com/content/348/bmj.g3432?tab=responses. Accessed September 22, 2014.

CORRECTION

ties. Dr Bratzler reported serving as a technical advisor and consultant for OFMQ and Telligen, being employed as full-time faculty for Oklahoma University Health Sciences Center, and receiving grant support from the Centers for Disease Control and Prevention. Dr Fine receives annual royalties from the chapter he authored titled “Community-Acquired Pneumonia in Adults: Risk Stratification and the Decision to Admit” published in UpToDate and has ownership of mutual funds that invest in companies in the health care sector. Missing Previous Presentation Information: In the Original Investigation titled “Association of Treatment With Carvedilol vs Metoprolol Succinate and Mortality in Patients With Heart Failure” published in the October 2014 issue of JAMA Internal Medicine (2014;174[10]:1597-1604. 10.1001/jamainternmed.2014.5792), the previous presentation information was missing. It should read as follows: Previous Presentation: This study was presented at the European Society of Cardiology Congress; August 31, 2014; Barcelona, Spain.

Missing Conflict of Interest Disclosure: In the Original Investigation titled “Effect of Bisphosphonate Use on Risk of Postmenopausal Breast Cancer: Results From the Randomized Clinical Trials of Alendronate and Zoledronic Acid” published in the October 2014 issue of JAMA Internal Medicine (2014;174[10]:1551-1558. doi:10 .1001/jamainternmed.2014.3634), there was an error in the Conflict of Interest Disclosures. The correct version reads as follows: “Dr Ensrud serves as a consultant on a data monitoring committee for Merck Sharp & Dohme. Dr Black has received grant support from Novartis and Merck and consulting, lecture, or advisory board fees from Lilly, Novartis, Amgen, Radius, and Merck. No other disclosures are reported.” This article was corrected online.

Error in Discussion: In the article titled “Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010,” published online August 25 and also in the October print issue of JAMA Internal Medicine (doi:10.1001 /jamainternmed.2014.4005), an incorrect term was used in the Discussion section. In the second paragraph, the first sentence should have read as follows: “Approximately 60% of all opioid analgesic overdoses occur among patients who have legitimate prescriptions from a single provider.26” This article was corrected online and in print.

Error in Conflict of Interest Disclosures: In the Original Investigation titled “Quality of Care for Elderly Patients Hospitalized for Pneumonia in the United States, 2006 to 2010” published online September 8, 2014, in JAMA Internal Medicine (doi:10.1001/jamainternmed.2014.4501), there was an omission in the Conflict of Interest Disclosures. The paragraph should have read: Dr Hausmann reported receiving support from a Veterans Affairs Career Development Award (RCD 06-387). Dr Nsa and Ms Auden reported being employees of the Oklahoma Foundation for Medical Quality (OFMQ), a Centers for Medicare & Medicaid Services (CMS) contractor, and participated in the study as part of their employment du-

Error in Table 3: In the article titled “The Quality of Supportive Cancer Care in the Veterans Affairs Health System and Targets for Improvement,” published online October 14, 2013, and also in the December 9/23, 2013, print issue of JAMA Internal Medicine (2013;173[22]:2071-2079. doi:10.1001/jamainternmed.2013.10797), an incorrect quality indicator statement appeared on page 2076 in Table 3. In that table, the quality indicator statement for quality indicator 80 should have read as follows: “IF a patient is newly known to have advanced cancer after a surgery, diagnostic test, or physical examination…THEN a discussion including prognosis and advance care planning should be documented within 1 mo or a reason why such a discussion did not occur.” This article was corrected online.

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New EMA policy-further measures needed to support comparative effectiveness assessments.

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