- Email: [email protected]
GSK Nixing Physician Dollars
GSK Nixing Physician Dollars Other Companies Not to Follow Suit
lucrative speakers bureaus, provide ghostwriting services for peer-reviewed papers, and pay big consulting fees.” The GSK changes come as several factors are combining to increase transparency and reduce the influence that the marketing arms of drug companies have on physician decisions.
HERE COMES THE SUN by ERIC BERGER Special Contributor to Annals News & Perspective
A
t a time when several forces have aligned to rein in the practice of using physicians to promote pharmaceuticals, the British drug company GlaxoSmithKline (GSK) announced in December it will no longer pay physicians to market its products. “We believe that it is imperative that we continue to actively challenge our business model at every level to ensure we are responding to the needs of patients and meeting the wider expectations of society,” Andrew Witty, chief executive officer of GSK said at the time. “We recognize that we have an important role to play in providing doctors with information about our medicines, but this must be done clearly, transparently, and without any perception of conflict of interest.” Among the specific reforms the company promised to make were not paying physicians to speak on behalf of GSK products at medical conferences and no longer compensating drug representatives on the number of prescriptions that physicians write. Instead, the company said, sales representatives will be evaluated and rewarded for their technical knowledge, the quality of the service they deliver to support improved patient care, and the overall performance of GSK’s business. The company plans to implement the changes for compensating drug representatives by early 2015 and end direct compensation for physicians by 2016. The
Volume 63, no. 6 : June 2014
proposed changes were met with a mix of hope and skepticism in the community of health care that tracks medical ethics. “I’m not sure exactly why they moved this way, right now, but from an industry perspective I do think it is important,” said Nathan Allen, MD, an assistant professor of medicine and medical ethics at Baylor College of Medicine in Houston, TX. “It’s probably a continued step in the right direction to make sure that providers aren’t unduly influenced by industry.” Much of the fight to reform the way in which pharmaceutical companies have marketed their products has taken place at medical colleges such as Baylor, where students have been active in campaigns to reduce the influence of marketing representatives. “This is a growing trend, and we hope that other pharmaceutical companies will take GSK’s lead and end the practice of paying physicians to endorse their products,” said Nida Degesys, MD, president of the American Medical Student Association. Still, much skepticism remained about the efficacy of the proposed changes. On the Web site of the magazine Scientific American, which frequently publishes articles about medical ethics, executive editor Fred Guterl wrote, “In an industry rife with conflicts of interest, this move is welcome news for consumers. It is unlikely, however, to have much effect. Entanglements between researchers and drug companies are thick. Drug firms have many ways of enriching favored doctors and researchers—they include them as members of
O
ne factor is the Physician Payments Sunshine Act, passed into law in 2010 as part of the Patient Protection and Affordable Care Act, but which is only now coming into effect. Beginning in August 2013, the law required pharmaceutical manufacturers to collect data about payments and gifts made by drug and medical device companies to physicians and teaching hospitals. The Centers for Medicare & Medicaid Services has set June 30, 2014, as a target date by which physicians can access data about their August 1 through December 31 report. Then, by September 30, CMS expects to release the data publicly through a searchable Web site. “The goal is to help inform consumers and patients in all medical fields about financial relationships between drug makers and doctors, with uniform disclosure,” said US Sen. Charles Grassley, R-Iowa, who coauthored the legislation creating the act. “The public deserves a much better picture of the drug industry’s financial presence in medicine than it has today.” Grassley said he was spurred to write the legislation after several high-profile cases of questionable financial relationships between drug companies and physicians. For example, he cited the resignation of Charles Nemeroff, MD, as chairman of psychiatry at Emory University in 2008. An Emory investigation of Dr. Nemeroff turned up more than $800,000 in income from GSK for more than 250 speaking engagements during 6 years that the professor did not disclose to the university. Annals of Emergency Medicine 19A
Although the United Kingdom–based GSK did not cite the US disclosure law in its decision to stop direct compensation to physicians for speaking engagements, medical ethicists believe the act must have at least influenced the company. “I don’t know if it’s in direct response to that, but I think it is a continuation of changes we’ve seen in the industry,” said Dr. Allen, the Baylor ethicist. “At least some of those are in the spirit of what is in the Sunshine Act.”
DOLLARS FOR DOCS
A
nother force for shining sunlight on the practice of paying physicians has been an ongoing investigation by Pro Publica, an independent, nonprofit newsroom, titled “Dollars for Docs.” Collected from various public disclosures, the Dollars for Docs database contains records of more than $2 billion in payments to physicians, other medical providers, and health care institutions by 15 pharmaceutical companies since 2009. In a 2010 report, the news organization found that 43 physicians had earned $200,000 between 2009 and early 2010, according to reports from 7 companies that had publicly disclosed such payments to date: GlaxoSmithKline, AstraZeneca, Eli Lilly and Co, Pfizer, Cephalon, Merck & Co, and Johnson & Johnson. Earnings were almost certainly much higher, the news organization said, noting that some 70 drug companies had not reported all of their paid speakers and consultants. Of the 384 providers whom Pro Publica identified as receiving $100,000 or more between 2009 and early 2010, just 1 was certified in emergency medicine, New York City–based John Cahill, MD, who received $165,800 from GSK in speakers fees. A third factor has been the PharmFree Campaign, launched by the American Medical Students Association in 2002. The campaign, active in medical schools, encourages all physicians-in-training and health care providers to eschew gifts from drug companies and seek out evidencebased and unbiased sources of information rather than to rely on pharmaceutical industry representatives for education. In 2007, the campaign launched its PharmFree Scorecard, which ranks US
20A Annals of Emergency Medicine
medical schools according to their policies to limit the access and influence of pharmaceutical companies and their representatives at schools and academic teaching centers. Now in its second decade of existence, the campaign has succeeded in training half a generation of physicians in the ways in which pharmaceutical companies can subtly and not-so-subtly influence their decisions as caregivers. “During the last decade, there has been increased education down to the medical school level on the impact of relationships between physicians and organizations, and people have become much more aware of these concerns,” Dr. Allen said. “We have seen changes that have gradually come about at many academic hospitals and centers, including reducing access by industry representatives and decreases in the numbers of free meals provided for physicians in the hospital settings.” So will the GSK decision to step back from directly paying physician speaker fees have much of an influence on the rest of the industry? To answer the question, Annals News & Perspective reached out to the Pharmaceutical Research and Manufacturers of America, as well as several of the world’s largest drug companies. PhRMA, the industry trade group, defended the current practice of paying physicians speaker’s fees to promote drug industry products. “PhRMA believes that the exchange of information between biopharmaceutical and health care professionals is vitally important to improved patient care and better treatments,” said Matthew Bennett, senior vice president at PhRMA. The trade group added that drug companies are continually seeking new ways to “optimize the flow of information with physicians.”
NOT FOLLOWING SUIT
H
owever, none of the drug companies contacted by Annals appeared to be prepared to follow GSK’s lead by enacting substantial reforms, at least not immediately. “We don’t have plans to change our practices at this time,” said Julie Masow, a
spokeswoman for Novartis, the Switzerlandbased drug manufacturer. “We support transparency in the relationships between health care companies and health care professionals and are committed to ensuring that physicians and patients have the information they need to make informed health care decisions.” Another Swiss company, Roche, also indicated that the GSK decision would have no effect on its operations and that neither would the Sunshine Act’s coming into full force later in 2014. “We have no plans to discontinue payments to health care professionals for speaking engagements, attendance at medical conferences, or other work,” said Nadine Pinell, a spokeswoman for Genentech, the US-based subsidiary of Roche. “The Sunshine Act does not change our health care compliance policies on interactions with health care professionals. Our aim is to provide health care professionals with the most important and relevant clinical information about our products and services so they can be best informed in treating patients.” Nevertheless, Pinell said, Genentech and Roche fully support the industry movement toward increased transparency of financial relationships. Genentech has developed an online tool, Sunshine Track, that will enable physicians to review their reportable payments and other transfers of value from Genentech before they are reported to the government. The US-based multinational company Johnson & Johnson also indicated no immediate plans for changing its practices. “While we continuously look for opportunities to strengthen our efforts, we are confident in our work to educate the medical community about the safety, efficacy, and appropriate use of our [Food and Drug Administration]–approved products,” said Mark Wolfe, a spokesman for the company. “Our approach has been—and will continue to be—focused on enhancing the health of patients through transparent, compliant communications.” Another US-based company, Pfizer, also said it valued the use of speaker’s fees. “Peer-to-peer education remains a valid and valuable means of communicating the safe and effective use of our medicines,” said Volume 63, no. 6 : June 2014
Dean Mastrojohn, director of Global Media Relations for the company. “Pfizer implements rigorous transparency protocols and speaker selection criteria to alleviate the potential for any conflict of interest among industry and physicians and to ensure that appropriately experienced individuals are selected to speak on behalf of the company. We compensate health care professionals, clinical investigators, and institutions for the educational work they do with Pfizer in a fair and transparent way.” The large French pharmaceutical company Sanofi-Aventis said it recognized the increasing global demands for transparency in the relationship between drug companies and the physicians who prescribe medicine. And although the company intended to comply with regulations such as those in the Sunshine Act, it did not plan to amend its practices. “The work done by health care professionals needs to be compensated in a fair and transparent manner,” said Mary Kathryn Steel, director of Media Relations
and Public Affairs for Sanofi US. “Sanofi intends to provide them with a level of payment that constitutes a fair remuneration with the respect to well-defined activities agreed contractually in advance, within the framework of clear parameters that depend on specific country environment and regulations. Indeed, since more than a decade, various rules and regulations governing transparency in the interactions between health care professionals and the pharmaceuticals industry have been set up, especially in France, United Kingdom, and the US. We are committed to be compliant with all applicable rules and regulations governing our relations with health care professionals.” Dr. Allen, the medical ethicist, said increasing transparency should help continue to increase cognizance of the conflict of interest issue within the physician community. And although it’s good that some pharmaceutical companies are taking steps to limit such conflicts,
In Sepsis, a Report of No Difference May Make a Lot of Difference by WILLIAM B. MILLARD, PhD Special Contributor to Annals News & Perspective
A
report from the first of 3 major trials of contrasting approaches to sepsis treatment suggests that a piece of embattled ground may be shifting. The Protocolized Care for Early Septic Shock (ProCESS) trial is the American entry in a coordinated 3-study effort that also includes the Australasian Resuscitation in Sepsis Evaluation (ARISE) and Protocolised Management in Sepsis (ProMISe) studies. All 3 investigations both build on and scrutinize the 2001 findings of
Volume 63, no. 6 : June 2014
Emanuel P. Rivers, MD, MPH, and colleagues at Detroit’s Henry Ford Hospital in a landmark article1 that promoted early goal-directed therapy (EGDT) as a best practice in sepsis care. The results of ProCESS appeared last March 18,2 finding no significant differences in clinical outcomes among 3 approaches: EGDT; protocol-based standard care not requiring central venous catheterization, administration of inotropes, or blood transfusions; and “usual care.” In what University of Pittsburgh professor of emergency medicine and ProCESS investigator Donald Yealy, MD, described as an expansion on Dr. Rivers’s
perhaps physicians should take some of the initiative on themselves. “We own some of the blame in the medical community for becoming overly reliant on other sources to educate ourselves about medications instead of developing our own bias-free educational sources,” he said. Section editor: Truman J. Milling, Jr, MD Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www. icmje.org). The author has stated that no such relationships exist. The views expressed in News and Perspective are those of the authors, and do not reflect the views and opinions of the American College of Emergency Physicians or the editorial board of Annals of Emergency Medicine. http://dx.doi.org/10.1016/j.annemergmed. 2014.04.009
work, ProCESS suggests that the key term in the phrase early goal-directed therapy is the first one. Early recognition and aggressive response are probably responsible for the advances the field has made since Dr. Rivers’s article appeared, an inference that will be strengthened if the forthcoming studies are consistent with the findings of ProCESS. Catheterization and the associated ScVO2 monitoring appear optional, not essential. Severe sepsis lacks the drama of acute myocardial infarction or stroke, but it is comparably menacing when assessed in absolute numbers—exceeding 750,000 cases a year around the time of the report by Dr. Rivers3 and described more recently as increasing4—and even more lethal, with short-term mortality of 20% or more even after the past decade’s advances. “One out of 5 people who come in with a heart attack don’t die,” Dr. Yealy noted. He sees the new findings supporting a timing-based detection and treatment paradigm comparable to that established for myocardial infarction. Although there is no identifiable threshold analogous to the golden hour, “what we know is the earlier Annals of Emergency Medicine 21A
lucrative speakers bureaus, provide ghostwriting services for peer-reviewed papers, and pay big consulting fees.” The GSK changes come as several factors are combining to increase transparency and reduce the influence that the marketing arms of drug companies have on physician decisions.
HERE COMES THE SUN by ERIC BERGER Special Contributor to Annals News & Perspective
A
t a time when several forces have aligned to rein in the practice of using physicians to promote pharmaceuticals, the British drug company GlaxoSmithKline (GSK) announced in December it will no longer pay physicians to market its products. “We believe that it is imperative that we continue to actively challenge our business model at every level to ensure we are responding to the needs of patients and meeting the wider expectations of society,” Andrew Witty, chief executive officer of GSK said at the time. “We recognize that we have an important role to play in providing doctors with information about our medicines, but this must be done clearly, transparently, and without any perception of conflict of interest.” Among the specific reforms the company promised to make were not paying physicians to speak on behalf of GSK products at medical conferences and no longer compensating drug representatives on the number of prescriptions that physicians write. Instead, the company said, sales representatives will be evaluated and rewarded for their technical knowledge, the quality of the service they deliver to support improved patient care, and the overall performance of GSK’s business. The company plans to implement the changes for compensating drug representatives by early 2015 and end direct compensation for physicians by 2016. The
Volume 63, no. 6 : June 2014
proposed changes were met with a mix of hope and skepticism in the community of health care that tracks medical ethics. “I’m not sure exactly why they moved this way, right now, but from an industry perspective I do think it is important,” said Nathan Allen, MD, an assistant professor of medicine and medical ethics at Baylor College of Medicine in Houston, TX. “It’s probably a continued step in the right direction to make sure that providers aren’t unduly influenced by industry.” Much of the fight to reform the way in which pharmaceutical companies have marketed their products has taken place at medical colleges such as Baylor, where students have been active in campaigns to reduce the influence of marketing representatives. “This is a growing trend, and we hope that other pharmaceutical companies will take GSK’s lead and end the practice of paying physicians to endorse their products,” said Nida Degesys, MD, president of the American Medical Student Association. Still, much skepticism remained about the efficacy of the proposed changes. On the Web site of the magazine Scientific American, which frequently publishes articles about medical ethics, executive editor Fred Guterl wrote, “In an industry rife with conflicts of interest, this move is welcome news for consumers. It is unlikely, however, to have much effect. Entanglements between researchers and drug companies are thick. Drug firms have many ways of enriching favored doctors and researchers—they include them as members of
O
ne factor is the Physician Payments Sunshine Act, passed into law in 2010 as part of the Patient Protection and Affordable Care Act, but which is only now coming into effect. Beginning in August 2013, the law required pharmaceutical manufacturers to collect data about payments and gifts made by drug and medical device companies to physicians and teaching hospitals. The Centers for Medicare & Medicaid Services has set June 30, 2014, as a target date by which physicians can access data about their August 1 through December 31 report. Then, by September 30, CMS expects to release the data publicly through a searchable Web site. “The goal is to help inform consumers and patients in all medical fields about financial relationships between drug makers and doctors, with uniform disclosure,” said US Sen. Charles Grassley, R-Iowa, who coauthored the legislation creating the act. “The public deserves a much better picture of the drug industry’s financial presence in medicine than it has today.” Grassley said he was spurred to write the legislation after several high-profile cases of questionable financial relationships between drug companies and physicians. For example, he cited the resignation of Charles Nemeroff, MD, as chairman of psychiatry at Emory University in 2008. An Emory investigation of Dr. Nemeroff turned up more than $800,000 in income from GSK for more than 250 speaking engagements during 6 years that the professor did not disclose to the university. Annals of Emergency Medicine 19A
Although the United Kingdom–based GSK did not cite the US disclosure law in its decision to stop direct compensation to physicians for speaking engagements, medical ethicists believe the act must have at least influenced the company. “I don’t know if it’s in direct response to that, but I think it is a continuation of changes we’ve seen in the industry,” said Dr. Allen, the Baylor ethicist. “At least some of those are in the spirit of what is in the Sunshine Act.”
DOLLARS FOR DOCS
A
nother force for shining sunlight on the practice of paying physicians has been an ongoing investigation by Pro Publica, an independent, nonprofit newsroom, titled “Dollars for Docs.” Collected from various public disclosures, the Dollars for Docs database contains records of more than $2 billion in payments to physicians, other medical providers, and health care institutions by 15 pharmaceutical companies since 2009. In a 2010 report, the news organization found that 43 physicians had earned $200,000 between 2009 and early 2010, according to reports from 7 companies that had publicly disclosed such payments to date: GlaxoSmithKline, AstraZeneca, Eli Lilly and Co, Pfizer, Cephalon, Merck & Co, and Johnson & Johnson. Earnings were almost certainly much higher, the news organization said, noting that some 70 drug companies had not reported all of their paid speakers and consultants. Of the 384 providers whom Pro Publica identified as receiving $100,000 or more between 2009 and early 2010, just 1 was certified in emergency medicine, New York City–based John Cahill, MD, who received $165,800 from GSK in speakers fees. A third factor has been the PharmFree Campaign, launched by the American Medical Students Association in 2002. The campaign, active in medical schools, encourages all physicians-in-training and health care providers to eschew gifts from drug companies and seek out evidencebased and unbiased sources of information rather than to rely on pharmaceutical industry representatives for education. In 2007, the campaign launched its PharmFree Scorecard, which ranks US
20A Annals of Emergency Medicine
medical schools according to their policies to limit the access and influence of pharmaceutical companies and their representatives at schools and academic teaching centers. Now in its second decade of existence, the campaign has succeeded in training half a generation of physicians in the ways in which pharmaceutical companies can subtly and not-so-subtly influence their decisions as caregivers. “During the last decade, there has been increased education down to the medical school level on the impact of relationships between physicians and organizations, and people have become much more aware of these concerns,” Dr. Allen said. “We have seen changes that have gradually come about at many academic hospitals and centers, including reducing access by industry representatives and decreases in the numbers of free meals provided for physicians in the hospital settings.” So will the GSK decision to step back from directly paying physician speaker fees have much of an influence on the rest of the industry? To answer the question, Annals News & Perspective reached out to the Pharmaceutical Research and Manufacturers of America, as well as several of the world’s largest drug companies. PhRMA, the industry trade group, defended the current practice of paying physicians speaker’s fees to promote drug industry products. “PhRMA believes that the exchange of information between biopharmaceutical and health care professionals is vitally important to improved patient care and better treatments,” said Matthew Bennett, senior vice president at PhRMA. The trade group added that drug companies are continually seeking new ways to “optimize the flow of information with physicians.”
NOT FOLLOWING SUIT
H
owever, none of the drug companies contacted by Annals appeared to be prepared to follow GSK’s lead by enacting substantial reforms, at least not immediately. “We don’t have plans to change our practices at this time,” said Julie Masow, a
spokeswoman for Novartis, the Switzerlandbased drug manufacturer. “We support transparency in the relationships between health care companies and health care professionals and are committed to ensuring that physicians and patients have the information they need to make informed health care decisions.” Another Swiss company, Roche, also indicated that the GSK decision would have no effect on its operations and that neither would the Sunshine Act’s coming into full force later in 2014. “We have no plans to discontinue payments to health care professionals for speaking engagements, attendance at medical conferences, or other work,” said Nadine Pinell, a spokeswoman for Genentech, the US-based subsidiary of Roche. “The Sunshine Act does not change our health care compliance policies on interactions with health care professionals. Our aim is to provide health care professionals with the most important and relevant clinical information about our products and services so they can be best informed in treating patients.” Nevertheless, Pinell said, Genentech and Roche fully support the industry movement toward increased transparency of financial relationships. Genentech has developed an online tool, Sunshine Track, that will enable physicians to review their reportable payments and other transfers of value from Genentech before they are reported to the government. The US-based multinational company Johnson & Johnson also indicated no immediate plans for changing its practices. “While we continuously look for opportunities to strengthen our efforts, we are confident in our work to educate the medical community about the safety, efficacy, and appropriate use of our [Food and Drug Administration]–approved products,” said Mark Wolfe, a spokesman for the company. “Our approach has been—and will continue to be—focused on enhancing the health of patients through transparent, compliant communications.” Another US-based company, Pfizer, also said it valued the use of speaker’s fees. “Peer-to-peer education remains a valid and valuable means of communicating the safe and effective use of our medicines,” said Volume 63, no. 6 : June 2014
Dean Mastrojohn, director of Global Media Relations for the company. “Pfizer implements rigorous transparency protocols and speaker selection criteria to alleviate the potential for any conflict of interest among industry and physicians and to ensure that appropriately experienced individuals are selected to speak on behalf of the company. We compensate health care professionals, clinical investigators, and institutions for the educational work they do with Pfizer in a fair and transparent way.” The large French pharmaceutical company Sanofi-Aventis said it recognized the increasing global demands for transparency in the relationship between drug companies and the physicians who prescribe medicine. And although the company intended to comply with regulations such as those in the Sunshine Act, it did not plan to amend its practices. “The work done by health care professionals needs to be compensated in a fair and transparent manner,” said Mary Kathryn Steel, director of Media Relations
and Public Affairs for Sanofi US. “Sanofi intends to provide them with a level of payment that constitutes a fair remuneration with the respect to well-defined activities agreed contractually in advance, within the framework of clear parameters that depend on specific country environment and regulations. Indeed, since more than a decade, various rules and regulations governing transparency in the interactions between health care professionals and the pharmaceuticals industry have been set up, especially in France, United Kingdom, and the US. We are committed to be compliant with all applicable rules and regulations governing our relations with health care professionals.” Dr. Allen, the medical ethicist, said increasing transparency should help continue to increase cognizance of the conflict of interest issue within the physician community. And although it’s good that some pharmaceutical companies are taking steps to limit such conflicts,
In Sepsis, a Report of No Difference May Make a Lot of Difference by WILLIAM B. MILLARD, PhD Special Contributor to Annals News & Perspective
A
report from the first of 3 major trials of contrasting approaches to sepsis treatment suggests that a piece of embattled ground may be shifting. The Protocolized Care for Early Septic Shock (ProCESS) trial is the American entry in a coordinated 3-study effort that also includes the Australasian Resuscitation in Sepsis Evaluation (ARISE) and Protocolised Management in Sepsis (ProMISe) studies. All 3 investigations both build on and scrutinize the 2001 findings of
Volume 63, no. 6 : June 2014
Emanuel P. Rivers, MD, MPH, and colleagues at Detroit’s Henry Ford Hospital in a landmark article1 that promoted early goal-directed therapy (EGDT) as a best practice in sepsis care. The results of ProCESS appeared last March 18,2 finding no significant differences in clinical outcomes among 3 approaches: EGDT; protocol-based standard care not requiring central venous catheterization, administration of inotropes, or blood transfusions; and “usual care.” In what University of Pittsburgh professor of emergency medicine and ProCESS investigator Donald Yealy, MD, described as an expansion on Dr. Rivers’s
perhaps physicians should take some of the initiative on themselves. “We own some of the blame in the medical community for becoming overly reliant on other sources to educate ourselves about medications instead of developing our own bias-free educational sources,” he said. Section editor: Truman J. Milling, Jr, MD Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www. icmje.org). The author has stated that no such relationships exist. The views expressed in News and Perspective are those of the authors, and do not reflect the views and opinions of the American College of Emergency Physicians or the editorial board of Annals of Emergency Medicine. http://dx.doi.org/10.1016/j.annemergmed. 2014.04.009
work, ProCESS suggests that the key term in the phrase early goal-directed therapy is the first one. Early recognition and aggressive response are probably responsible for the advances the field has made since Dr. Rivers’s article appeared, an inference that will be strengthened if the forthcoming studies are consistent with the findings of ProCESS. Catheterization and the associated ScVO2 monitoring appear optional, not essential. Severe sepsis lacks the drama of acute myocardial infarction or stroke, but it is comparably menacing when assessed in absolute numbers—exceeding 750,000 cases a year around the time of the report by Dr. Rivers3 and described more recently as increasing4—and even more lethal, with short-term mortality of 20% or more even after the past decade’s advances. “One out of 5 people who come in with a heart attack don’t die,” Dr. Yealy noted. He sees the new findings supporting a timing-based detection and treatment paradigm comparable to that established for myocardial infarction. Although there is no identifiable threshold analogous to the golden hour, “what we know is the earlier Annals of Emergency Medicine 21A