EDITORIALS Decision Making and Acute MIs D e c i s i o n m a k i n g u n d e r uncertainty 1 is often fraught with great difficulty when the data on which the decision is based are imprecise and poorly linked to predicted outcome. Clinical diagnosis is an example of such a setting. ~ Multiple disease states present with similar if not identical historical and clinical data, while singular diseases often do not present with the same historical and clinical data. The net result is that clinicians are often quite poor at making diagnostic decisions. No disease illustrates this diagnostic dilemma more aptly than the diagnosis of acute myocardial infarction. In addition to embodying all the problems alluded to above, acute myocardial infarction is a disease of low incidence with a major penalty for its misdiagnosis. The cost of missing the diagnosis is measured both in terms of potential morbidity and m o r t a l i t y for the p a t i e n t and of costly litigious actions for the physician. 3 The cost to society as a consequence of the overdiagnosis resulting from its low incidence has been conservatively estimated to approach $1 billion annually. 4 See related article, p 1220. The largest study measuring the a c c u r a c y with w h i c h p h y s i c i a n s make the diagnosis of acute myocardial infarction in patients presenting to the emergency department revealed a disappointing sensitivity and specificity of 88% and 71%, respectively. 4 This is not surprising in that no reliable historical or physical predictors of the presence of acute myocardial infarction seem to exist, s-8 and the most reliable early indicator of an acute myocardial infarction, the ECG, has been reported to be diagnostic in as few as 50% of patients. 9 Because approximately 7% to 8% of adult patients who present to the ED with anterior chest pain turn out to have sustained a myocardial infarction,1 this sensitivity and specificity would represent the misdiag20:11 November 1991
nosis of approximately ten patients who had sustained an acute myocardial infarction and 267 patients who had not sustained a myocardial infarction per 1,000 patients. Many attempts have been made to improve the physician's ability to make the early diagnosis of acute myocardial infarction. Some of these have included computer-based technologies, expert systems,4A ° diagnostic treatment algorithms, 11 and alternative admissions protocols. 12 To date, these strategies have either been unhelpful or remain untested. In the past, physicians have been admonished not to use CK determinations to influence diagnostic decisions regarding the admission of patients being evaluated for acute myocardial infarction. The reason for this was based mainly on the poor specificity of these determinations coupled with the inability to obtain the results of cardiac specific CK determinations expeditiously. 13,14 This problem appeared to have a potential solution with the development of the rapid CK-MB assay. Although a number of studies have documented impressive sensitivities and specificities for this assay, 15A6 no study to date has demonstrated that its use improves physician diagnostic accuracy. The work by Young et al in this issue of Annals may represent the first step in this direction. The authors report on the ability of the rapid CKMB enzyme analysis to affect physician judgment in what appears to be a positive direction. This may represent some needed help for this troubled diagnostic dilemma. The authors evaluated only the most problematic patients, those without ECG evidence of acute myocardial infarction on presentation. They also negatively weighted the study by allowing patients who sustained myocardial infarctions with elevated rapid CK-MB levels who were admitted early to be excluded. Even with this, the authors present evidence to suggest t h a t the use of the a s s a y strengthened physician decisions in one third of all cases. Annals of Emergency Medicine
Unfortunately, what may be more important is what is not reported in this work. The authors construct a compelling argument to support the fact t h a t t h e use of t h i s a s s a y strengthened physician judgment and behavior but fail to present conclusive evidence that this effect improved clinical practice. Although this work does suggest that the use of the assay did improve the cost effectiveness of patient admission by reducing the number of patients admitted to the coronary care unit, clearcut evidence to this effect was not reported. Evidence is presented indicating that the overall admission rate to the hospital for patients in whom the diagnosis of acute myocardial infarction was entertained was not reduced: Ultimately, the authors must demonstrate that the use of the assay improves patient care. Data must be presented to show that the correct identification of those patients who have sustained a myocardial infarction is improved by the use of the assay (improved sensitivity). T h e y must also demonstrate that use of the assay can allow the physician to reduce the large number of unneeded coronary care unit and hospital admissions of patients who have not sustained a myocardial infarction (improved specificity). In view of the fact that the rapid CK-MB assay, when used serially over three hours, has been shown to have a sensitivity and specificity of at least 90% and 95%, respectively, is this should be possible. It is hoped, as suggested, that this will be forthcoming in future investigations by these authors.
William G Baxt, MD University of California San Diego Medical Center 1. Holloway CA: Behavioral assumptions and limitations of decision analysis, in Holloway CA {ed): Decdsion-making Under Uncertainty: Models and Choices.
Englewood Cliffs, New Jersey, Prentice-Hall, 197% p 436-455. 2. Moskowitz AJ, Kuipers BJ, Kassirer JP: Dealing with uncertainty risk and trade-off in clinical decisions: A cognitive science approach. Ann Intern Med 1988;108: 435~449.
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EDITORIALS
3. Rusnak RA, Stair TO, Hansen K, et aI: Litigation against the emergency physician: Common features in cases of missed myocardial infarction. Ann Emerg Med 1989;18:1029q034. 4. Goldman L, Cook El:, Brand DA, et al: A computer protocol to predict myocardial infarction in emergency department patients with chest pain. N Engl J Med 1988;318:797-803. 5. Zarling EJ, Sexton H, Milnor P: Failure to diagnose acute myocardial infarction in emergency room patients with chest pain. JAMA 1983;250:1177-I181. 6. Kannel WB, Abbott RD: Incidence and prognosis of unrecognized myocardial infarction. An update on the Framingham Study. N EngI ] Med 1984;311:1144-1147.
absence of chest pain in patients with suspected acute myocardial infarction. Am J Emerg Med 1989;7:372-377. 9. McGuiness JB, Begg TB, Semple T: First electrocardiogram in recent myocardial infarction. Br Med J 1976;2:449-451. i0. Pozen MW, D'Agostino RB, Selker HP, et al: A predictive instrument to improve corona13r-care-unit admission practices in acute ischemic heart disease: A prospective multicenter clinical trial. N EngI J Med 1984;310:1273-I278. 11. Pozeu MW, Stechmiller JK, Voight GC: Prognostic efficacy of early clinical categorization of myocardial infarction patients. Circ~ilatJon 1977;56:816-819.
7. Klaeboe G, Otterstad JE, Winsnes T, et ah Predictive value of prodromal symptoms in myocardiK1 infarction. Acta ivied Scand 1987;222:27-30.
12. Lee TH, Juarez G, Cook ElZ, et aI: Ruling out acute myocardial infar-ction: A prospective multicenter validation of a i2-hour strategy for patients at low risk. N Engl J ivied 1990;324:1239-1246.
8. Fesmire FM, Wears RL: The utility of the presence or
13. Lee TH, Goldman L: Serum enzyme assays in the
diagnosis of acute myocardial infarction: Recommendations on acute quantitative analysis. Ann Intern Med 1986;105:221-233. 14. Eisenberg JM, Horowitz LN, Busch RR, et ah Diagnosis of acute myocardial infarction in the emergency room: A prospective assessment of cIinical decision making arid the usefuiness of immediate cardiac enzyme determination. J Commun Health I979;4:190-198. 15. Giblet WB, Lewis LM, Erb RE, et aI: Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic ECGs: Serial CK-MB sampling in the emergency department. Ann Emerg Med 1990;19:1389q366. 16. Green GB, Hansen KN, Fleetwood D, et aI; The usefulness of a rapid creatine phosphokinase (CPK) MB assay in the evaluation of emergency department patients with possible myocardial infarction (abstract). Ann Emerg Med 1990;19:1227.
I n f o r m e d C o n s e n t to R e s e a r c h on Emergency Care In the article, "Informed Consent for Biomedical Research in Acute Care Medicine," in this issue of Annals, Abramson, Iserson, McKay, and Cohen agree on the statement of the central ethical problem in research on emergency medical treatment: the conflict between the autonomy and welfare of subjects and the need to conduct research. This conflict is present in all medical research, but it is especially difficult to resolve for emergency research because subjects are likely to be unconscious or otherwise incapable of exercising autonomy through informed consent and because of the urgency of beginning treatment. The physicians (Abramson and Iserson) and the government official (McKay) present resolutions to the conflict that rely on the provisions for waiver of consent in the Department of Health and Human Services (DHHS) regulations for institutional review board (IRB) review of research. The attorney (Cohen) presents a legal challenge to the regulatory approach of his fellow panelists: courts will be responsive to arguments that the DHHS regulations do not sufficiently protect a subject's statutory, common law, or constitutional rights, and this places investigators at r i s k of liability even though the research was closely and thoroughly scrutinized by an IRB. 138/1267
Iserson and McKay argue that the impossibility of prospective consent requires that the risk:benefit ratio for subjects be strictly reviewed by IRBs and that these bodies adopt procedures to m o n i t o r the research. When subjects can give prospective consent, the IRB members can approve research on the assumption that individuals can make their own assessments of whether the risk:benefit ratio of being a subject compares favorably with that of receiving care outside the research protocol. When this assumption cannot be met, it sounds reasonable that an IRB should make its own more careful assessment. However, neither author provides more than an exhortation for this. They do not state the standards for stricter review and explain how they differ from those for nonstrict review. McKay identifies some questions that an IRB should ask, but they are questions an IRB should ask about any clinical research. This absence of standards is not limited to Iserson and McKay; one of the m o s t v e x i n g l a c u n a e in the DHHS regulations is the lack of any account of how an IRB should judge that "risks to subjects are reasonable in relation to anticipated benefits and the importance of the knowledge." Quantitative standards for weighing risk:benefit ratios are theoretAnnals of Emergency Medicine
ically dubious and practically unworkable. However, it is possible to present a qualitative comparison of the risk/benefit of being a subject in a trial and the risk/benefit of not being in the trial. Abramson's criteria for using deferred c o n s e n t to research, as well as my own criteria for research without prospective consent (discussed by Abramson), suggest a framework for doing this. For an IRB to make this comparison, protocols should contain a section in which the risks and benefits of being a subject in the trial are listed next to the risks and benefits of not being in the trial, and the differences explained. Protocols contain explanations of the possible benefits of the research, and a long list of the risks of the research treatments and related interventions. Seldom is a t t e n t i o n given to the comparative risks and benefits for the patients if they are not enrolled in the protocol. See related article, p 1251. Most IRB members will not have enough expertise in the area of the research to do the comparison for themselves. Even if they could, it is the burden of the investigator to justify the research to the IRB. Of course, the investigator can appear before the IRB and answer questions, 20:11 November 1991
nosis of approximately ten patients who had sustained an acute myocardial infarction and 267 patients who had not sustained a myocardial infarction per 1,000 patients. Many attempts have been made to improve the physician's ability to make the early diagnosis of acute myocardial infarction. Some of these have included computer-based technologies, expert systems,4A ° diagnostic treatment algorithms, 11 and alternative admissions protocols. 12 To date, these strategies have either been unhelpful or remain untested. In the past, physicians have been admonished not to use CK determinations to influence diagnostic decisions regarding the admission of patients being evaluated for acute myocardial infarction. The reason for this was based mainly on the poor specificity of these determinations coupled with the inability to obtain the results of cardiac specific CK determinations expeditiously. 13,14 This problem appeared to have a potential solution with the development of the rapid CK-MB assay. Although a number of studies have documented impressive sensitivities and specificities for this assay, 15A6 no study to date has demonstrated that its use improves physician diagnostic accuracy. The work by Young et al in this issue of Annals may represent the first step in this direction. The authors report on the ability of the rapid CKMB enzyme analysis to affect physician judgment in what appears to be a positive direction. This may represent some needed help for this troubled diagnostic dilemma. The authors evaluated only the most problematic patients, those without ECG evidence of acute myocardial infarction on presentation. They also negatively weighted the study by allowing patients who sustained myocardial infarctions with elevated rapid CK-MB levels who were admitted early to be excluded. Even with this, the authors present evidence to suggest t h a t the use of the a s s a y strengthened physician decisions in one third of all cases. Annals of Emergency Medicine
Unfortunately, what may be more important is what is not reported in this work. The authors construct a compelling argument to support the fact t h a t t h e use of t h i s a s s a y strengthened physician judgment and behavior but fail to present conclusive evidence that this effect improved clinical practice. Although this work does suggest that the use of the assay did improve the cost effectiveness of patient admission by reducing the number of patients admitted to the coronary care unit, clearcut evidence to this effect was not reported. Evidence is presented indicating that the overall admission rate to the hospital for patients in whom the diagnosis of acute myocardial infarction was entertained was not reduced: Ultimately, the authors must demonstrate that the use of the assay improves patient care. Data must be presented to show that the correct identification of those patients who have sustained a myocardial infarction is improved by the use of the assay (improved sensitivity). T h e y must also demonstrate that use of the assay can allow the physician to reduce the large number of unneeded coronary care unit and hospital admissions of patients who have not sustained a myocardial infarction (improved specificity). In view of the fact that the rapid CK-MB assay, when used serially over three hours, has been shown to have a sensitivity and specificity of at least 90% and 95%, respectively, is this should be possible. It is hoped, as suggested, that this will be forthcoming in future investigations by these authors.
William G Baxt, MD University of California San Diego Medical Center 1. Holloway CA: Behavioral assumptions and limitations of decision analysis, in Holloway CA {ed): Decdsion-making Under Uncertainty: Models and Choices.
Englewood Cliffs, New Jersey, Prentice-Hall, 197% p 436-455. 2. Moskowitz AJ, Kuipers BJ, Kassirer JP: Dealing with uncertainty risk and trade-off in clinical decisions: A cognitive science approach. Ann Intern Med 1988;108: 435~449.
1266/137
EDITORIALS
3. Rusnak RA, Stair TO, Hansen K, et aI: Litigation against the emergency physician: Common features in cases of missed myocardial infarction. Ann Emerg Med 1989;18:1029q034. 4. Goldman L, Cook El:, Brand DA, et al: A computer protocol to predict myocardial infarction in emergency department patients with chest pain. N Engl J Med 1988;318:797-803. 5. Zarling EJ, Sexton H, Milnor P: Failure to diagnose acute myocardial infarction in emergency room patients with chest pain. JAMA 1983;250:1177-I181. 6. Kannel WB, Abbott RD: Incidence and prognosis of unrecognized myocardial infarction. An update on the Framingham Study. N EngI ] Med 1984;311:1144-1147.
absence of chest pain in patients with suspected acute myocardial infarction. Am J Emerg Med 1989;7:372-377. 9. McGuiness JB, Begg TB, Semple T: First electrocardiogram in recent myocardial infarction. Br Med J 1976;2:449-451. i0. Pozen MW, D'Agostino RB, Selker HP, et al: A predictive instrument to improve corona13r-care-unit admission practices in acute ischemic heart disease: A prospective multicenter clinical trial. N EngI J Med 1984;310:1273-I278. 11. Pozeu MW, Stechmiller JK, Voight GC: Prognostic efficacy of early clinical categorization of myocardial infarction patients. Circ~ilatJon 1977;56:816-819.
7. Klaeboe G, Otterstad JE, Winsnes T, et ah Predictive value of prodromal symptoms in myocardiK1 infarction. Acta ivied Scand 1987;222:27-30.
12. Lee TH, Juarez G, Cook ElZ, et aI: Ruling out acute myocardial infar-ction: A prospective multicenter validation of a i2-hour strategy for patients at low risk. N Engl J ivied 1990;324:1239-1246.
8. Fesmire FM, Wears RL: The utility of the presence or
13. Lee TH, Goldman L: Serum enzyme assays in the
diagnosis of acute myocardial infarction: Recommendations on acute quantitative analysis. Ann Intern Med 1986;105:221-233. 14. Eisenberg JM, Horowitz LN, Busch RR, et ah Diagnosis of acute myocardial infarction in the emergency room: A prospective assessment of cIinical decision making arid the usefuiness of immediate cardiac enzyme determination. J Commun Health I979;4:190-198. 15. Giblet WB, Lewis LM, Erb RE, et aI: Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic ECGs: Serial CK-MB sampling in the emergency department. Ann Emerg Med 1990;19:1389q366. 16. Green GB, Hansen KN, Fleetwood D, et aI; The usefulness of a rapid creatine phosphokinase (CPK) MB assay in the evaluation of emergency department patients with possible myocardial infarction (abstract). Ann Emerg Med 1990;19:1227.
I n f o r m e d C o n s e n t to R e s e a r c h on Emergency Care In the article, "Informed Consent for Biomedical Research in Acute Care Medicine," in this issue of Annals, Abramson, Iserson, McKay, and Cohen agree on the statement of the central ethical problem in research on emergency medical treatment: the conflict between the autonomy and welfare of subjects and the need to conduct research. This conflict is present in all medical research, but it is especially difficult to resolve for emergency research because subjects are likely to be unconscious or otherwise incapable of exercising autonomy through informed consent and because of the urgency of beginning treatment. The physicians (Abramson and Iserson) and the government official (McKay) present resolutions to the conflict that rely on the provisions for waiver of consent in the Department of Health and Human Services (DHHS) regulations for institutional review board (IRB) review of research. The attorney (Cohen) presents a legal challenge to the regulatory approach of his fellow panelists: courts will be responsive to arguments that the DHHS regulations do not sufficiently protect a subject's statutory, common law, or constitutional rights, and this places investigators at r i s k of liability even though the research was closely and thoroughly scrutinized by an IRB. 138/1267
Iserson and McKay argue that the impossibility of prospective consent requires that the risk:benefit ratio for subjects be strictly reviewed by IRBs and that these bodies adopt procedures to m o n i t o r the research. When subjects can give prospective consent, the IRB members can approve research on the assumption that individuals can make their own assessments of whether the risk:benefit ratio of being a subject compares favorably with that of receiving care outside the research protocol. When this assumption cannot be met, it sounds reasonable that an IRB should make its own more careful assessment. However, neither author provides more than an exhortation for this. They do not state the standards for stricter review and explain how they differ from those for nonstrict review. McKay identifies some questions that an IRB should ask, but they are questions an IRB should ask about any clinical research. This absence of standards is not limited to Iserson and McKay; one of the m o s t v e x i n g l a c u n a e in the DHHS regulations is the lack of any account of how an IRB should judge that "risks to subjects are reasonable in relation to anticipated benefits and the importance of the knowledge." Quantitative standards for weighing risk:benefit ratios are theoretAnnals of Emergency Medicine
ically dubious and practically unworkable. However, it is possible to present a qualitative comparison of the risk/benefit of being a subject in a trial and the risk/benefit of not being in the trial. Abramson's criteria for using deferred c o n s e n t to research, as well as my own criteria for research without prospective consent (discussed by Abramson), suggest a framework for doing this. For an IRB to make this comparison, protocols should contain a section in which the risks and benefits of being a subject in the trial are listed next to the risks and benefits of not being in the trial, and the differences explained. Protocols contain explanations of the possible benefits of the research, and a long list of the risks of the research treatments and related interventions. Seldom is a t t e n t i o n given to the comparative risks and benefits for the patients if they are not enrolled in the protocol. See related article, p 1251. Most IRB members will not have enough expertise in the area of the research to do the comparison for themselves. Even if they could, it is the burden of the investigator to justify the research to the IRB. Of course, the investigator can appear before the IRB and answer questions, 20:11 November 1991
