Letters Conflict of Interest Disclosures: None reported. 1. Williams SV, Eisenberg JM. A controlled trial to decrease the unnecessary use 1. Fisher ES, Wennberg DE, Stukel TA, Gottlieb DJ, Lucas FL, Pinder EL. of diagnostic tests. J Gen Intern Med. 1986;1(1):8-13. doi:10.1007/BF02596318 The implications of regional variations in Medicare spending, part 1: the content, 2. Geleris JD, Shih G, Logio L. Analysis of diagnostic test ordering habits among quality, and accessibility of care. Ann Intern Med. 2003;138(4):273-287. doi:10 internal medicine residents [published online October 8, 2018]. JAMA Intern Med. .7326/0003-4819-138-4-200302180-00006 doi:10.1001/jamainternmed.2018.3519 2. Weinberger SE. Providing high-value, cost-conscious care: a critical seventh general competency for physicians. Ann Intern Med. 2011;155(6):386-388. doi:10.7326/0003-4819-155-6-201109200-00007 Prohibited Stimulants in Dietary Supplements 3. Asch DA, Nicholson S, Srinivas S, Herrin J, Epstein AJ. Evaluating obstetrical After Enforcement Action by the US Food and Drug residency programs using patient outcomes. JAMA. 2009;302(12):1277-1283. Administration doi:10.1001/jama.2009.1356 The US Food and Drug Administration (FDA) is responsible for 4. Kahneman D, Rosenfield AM, Gandhi L, Blaser T. Noise: how to overcome the eliminating adulterated and potentially hazardous dietary supple- high, hidden cost of inconsistent decision making. https://hbr.org/2016/10 /noise. Published October 2016. Accessed January 30, 2018. ments from the marketplace. The FDA uses a variety of enforce- 5. O’Brien DK, Flood J, Wesley R. Resident test ordering patterns. Fam Pract Res ment actions, including public notices, to remove potentially J. 1987;7(1):42-50. hazardous ingredients. How- 6. Dine CJ, Bellini LM, Diemer G, et al. Assessing correlations of physicians’ ever, it is not known whether Editor's Note page 1723 practice intensity and certainty during residency training. J Grad Med Educ. public notices are effective. We 2015;7(4):603-609. doi:10.4300/JGME-D-15-00092.1 explored the effectiveness of the FDA’s public notices issued be- tween 2013 and 2016 targeting prohibited sympathomimetic Editor's Note stimulants in supplements. We analyzed supplements purchased The Persistent Problem of Overuse of Diagnostic in 2014 and the same brands purchased again in 2017 to deter- Testing Among House Staff—Time to Move Forward mine the presence of prohibited stimulants before and after the I was a second-year medical student at the University of Penn- FDA issued public notices. sylvania, Philadelphia, in 1978, and I had the immense good for- tune to work with Sankey Williams, MD, and John Eisenberg, MD. Methods | From January 1, 2013, to December 31, 2016, the They were performing a trial to evaluate the influence of educa- FDA issued notices regarding 4 prohibited sympathomimetic tion on reducing house staff use of unnecessary inpatient labo- stimulants: 1,3-dimethylamylamine (1,3-DMAA), 1,3- ratory testing.1 The educational intervention had no benefit on dimethylbutylamine (DMBA), β-methylphenylethylamine house staff ordering behavior, but it had resounding effects on (BMPEA), and methylsynephrine (oxilofrine).1-4 The FDA how I came to view routine use of many different types of test- notices regarding ingredients in supplements not catego- ing and treatments that I had previously assumed were evidence rized as sympathomimetic stimulants, such as picamilon, based. That early research experience led me to carefully ques- were excluded from the current analysis. We previously ana- tion the evidence base for many commonly used tests and pro- lyzed all supplements on sale in 2014 listing Acacia rigidula cedures: How will the information from this test help me to take as an ingredient for the presence of 1 stimulant, BMPEA.1 For better care of my patient? Will it lead to better outcomes? Could the current study, we purchased the same brands of supple- I have gotten there without the use of this test? ments in 2017. Supplements purchased in 2014 were reana- The Research Letter by Geleris et al2 in this issue of JAMA lyzed for 1,3-DMAA, DMBA, and oxilofrine, and supplements Internal Medicine brought back my 40-year-old memories of purchased in 2017 were analyzed for all 4 prohibited stimu- research on the overuse of diagnostic testing by house staff. lants subject to FDA enforcement action. As previously Clearly, the problem has not gone away. In their study, Geleris described,1 liquid chromatography–quadrupole time-of- et al2 found that there is tremendous variation in inpatient labo- flight mass spectrometry was used to analyze the supple- ratory test and radiology test ordering among the house staff, ments, and the presence of each stimulant was confirmed by an indicator (particularly when outcomes do not differ) of ques- accurate mass, retention time, isotope pattern, and at least 1 tionable or unnecessary care, and we publish studies like this fragment ion in the mass spectra. one to keep the conversation moving forward. Medicine re- mains largely an apprenticeship. The practice patterns that resi- Results | Of the 21 brands of supplements analyzed in 2014, a dents develop are likely to persist throughout their careers. total of 12 brands (57%) were still available for purchase in 2017. Residency is the perfect time to think clearly and deeply what The 12 brands that were available in both 2014 and 2017 were can be learned from each potential test and to order only those included in the current analysis (Table). In 2013, the FDA is- tests that will affect the care of the patient. sued a public notice about the use of 1,3-DMAA. Of the 12 supplements purchased in 2014, 1,3-DMAA was present in 6 Rita F. Redberg, MD, MSc (50%). The FDA issued notices about the use of DMBA and BMPEA in 2015 and oxilofrine in 2016. Of the 12 supplements Author Affiliations: Department of Medicine, University of California, purchased in 2017, a total of 9 (75%) contained at least 1 of the San Francisco; Editor, JAMA Internal Medicine. 4 stimulants subject to FDA notices, and 6 (50%) contained 2 Published Online: October 8, 2018. doi:10.1001/jamainternmed.2018.3503 or more. One stimulant, DMBA, was not detected in any supple- Corresponding Author: Rita F. Redberg, MD, Department of Medicine, University of California, San Francisco, 505 Parnassus, Room M1180, ment purchased in 2014. After the FDA issued a public notice San Francisco, CA 94143 ([email protected]). about DMBA in 2015, DMBA was detected in 4 of the 12 supple- Conflict of Interest Disclosures: None reported. ments (33%) purchased in 2017. jamainternalmedicine.com (Reprinted) JAMA Internal Medicine December 2018 Volume 178, Number 12 1721 © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Letters Abbreviations: BMPEA, indicates Table. Quantities of 4 Experimental Stimulants Subject to FDA Public Notices in Supplements β-methylphenylethylamine; Purchased in 2014 and 2017 DMBA, 1,3-dimethylbutylamine; BMPEA,b Mean 1,3-DMAA,c Mean DMBA,d Mean (SD), 1,3-DMAA, 1,3-dimethylamylamine; Claim on Label (SD), mg per Pill (SD), mg per Pill mg per Pill Oxilofrine,e Mean (SD), FDA, US Food and Drug Producta or Website or Capsule or Capsule or Capsule mg per Pill or Capsule Administration; ND, not detectable. Supplements Purchased in 2014 a Coded indicator of the product. A Cognitive function ND ND ND 0.07 (0.04) b β-Methylphenylethylamine is not B Weight loss ND ND ND 54.31 (0.82) approved for use in humans. Quantities of BMPEA in products C Weight loss 18.71 (2.16) 36.70 (11.91)f ND 34.07 (10.06) purchased in 2014 were previously D Weight loss 5.74 (1.15) ND ND 26.48 (2.56) reported.1 E Weight loss 27.35 (5.87) 34.68 (0.89)f ND 34.31 (2.06) c 1,3-Dimethylamylamine is a 1940s F Weight loss ND ND ND 0.31 (0.04) to 1960s nasal decongestant (Eli Lilly & Co) that was withdrawn G Sports supplement 3.22 (0.67) ND ND 7.78 (0.49) from the market in the 1970s. It was H Sports supplement 31.23 (5.72) ND ND 31.07 (1.94) never approved for oral use. I Weight loss 9.89 (1.26) 12.17 (1.23)f ND 25.62 (1.53) d 1,3-Dimethylbutylamine is not J Weight loss 3.35 (0.74) 12.03 (1.31)f ND 37.45 (1.21) approved for use in humans. e K Weight loss 0.97 (0.31) 11.39 (1.74)f ND 40.75 (5.31) Oxilofrine was previously available in several European countries. It f L Weight loss 23.05 (2.79) 26.89 (6.05) ND 37.44 (7.43) increased blood pressure and Supplements Purchased in 2017 cardiac output and was available in A Cognitive function ND ND ND 0.05 (0.01)f 16- to 40-mg capsules. It was never approved for use in the United f B Weight loss ND ND ND 40.84 (6.48) States. f f C Weight loss ND ND 30.43 (3.26) 7.09 (0.91) f Quantities represent stimulants in D Weight loss ND ND ND 28.38 (0.82)f supplements after the FDA issued a public notice about the stimulant. Eg Weight loss 17.23 (1.47)f 36.12 (5.45)f ND 27.43 (1.06)f The date of the FDA warning for F Weight loss ND ND ND ND 1,3-DMAA was July 2013; DMBA, G Sports supplement ND ND ND ND April 2015; BMPEA, April 2015; and oxilofrine (referred to as H Sports supplement ND ND ND ND methylsynephrine), April 2016.