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Clinical trials of informed consent
SUSPENDED JUDGMENT Clinical Trials of Informed Consent David L. Simel, MD, MHS, and John R. Feussner, MD Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, and the Division of General Internal Medicine, Duke University, Durham, North Carolina
Informed consent is a tenet of clinical care and clinical research that has been accepted by many without proof that the process works. Informed consent seems ethically correct. We recognize our moral obligation to tell patients about the treatment plan, intended benefits, possible side effects, and alternative therapies. Despite this moral imperative, some clinicians are discomfited by the informed consent process. They question whether informed consent is really "informed," whether patients consent freely or under duress caused by their illness; and they wonder whether informed consent is a mere legal obligation with little connection to the realities of medical treatment. These concerns are reasonable ones, but until recently they have been more a subject of debate rather than empirical research. As clinicians and clinical trialists, we have an obligation to approach empirically the issues of informed consent as rigorously as we approach the design, conduct, and analyses of trials themselves. This scientific approach to understanding the informed consent process will allow us to realize more fully the intended goals of informed consent [1]. We define empirical research on informed consent as the study of actual informed consent decisions by patients or their proxies with regard to consent, and the impact of consent on patients or clinical trial outcome. "Actual" consent decisions occur when patients believe they are making a real decision about treatment or participation in a clinical trial. This definition of empirical informed consent research should address some of the limitations that characterize previous research on informed consent as outlined by Meisel and Roth [2,3]. Some limitations include (1) use of nonpatient subjects or hypothetical situations, (2) failure to consider what physicians actually told the patient, (3) focusing only on patient recall as the key to understanding, (4) lack of generalizability, and (5) allowing investigator bias where the investigator was also the patient's physician. Research using hypothetical scenarios,
Address reprint requests to: David L. Simel, MD, MHS, Ambulatory Care, Department of Veterans Affairs Medical Center, 508 Fulton Street, Durham, NC 27705. Received December 10, 1991; revised March 11, 1992. Controlled Clinical Trials 13:321-324 (1992) © Elsevier Science Publishing Co., Inc. 1992 655 A v e n u e of the Americas, N e w York, N e w York 10010
321 0197-2456/92/$5.00
322
D.L. Sirnel and J.R. Feussner evaluating patient recall, or assessing only the patient's knowledge base after making their consent decision supplement empirical informed consent research, but such studies can not address the central issue of the patient's actual decision. We conducted a study of empirical informed consent to evaluate the impact of simple quantitative information on consent decisions [3]. We designed a sham trial in which randomized patients received one of two consent forms. One study (consent A) described a randomized trial of a new medication that may work "twice as fast as usual treatment," while the second (consent B) described a trial of a new medication that may work "half as fast as usual treatment." This experiment had several important design features that addressed some of the limitations of previous research: (1) we studied patients making real decisions; (2) we tape-recorded all patient-physician interactions and submitted them to an independent third party who documented that the presentations were unbiased and not coercive; (3) we did not confine our analysis to an assessment of patient recall; (4) we increased generalizability by studying patients with a variety of symptoms who presented to an urgentcare ambulatory clinic for evaluation; and (5) we decreased investigator bias by not having the patient's physician obtain the informed consent. Our a priori hypothesis had two components: (1) consent rates would be improved in an appropriate direction when patients did cite quantitative information as a factor, and (2) consent rates would be similar when patients did not cite quantitative information as a factor in their decision. Patients did not consent to the trials equally, and consent was strongly affected by the severity of their symptoms that led them to seek medical care. Patients who cited the quantitative information when they made their decision were highly likely to consent to study A (95% consented) and unlikely to consent to study B (64% did not consent; Table 1) [3]. Among patients who received consent A and cited quantitative information, 19/20 wanted a medicine that was twice as fast; among patients who received consent B and cited quantitative information, 14/16 declined because they wanted a faster medication. Consent rates for patients who did not cite quantitative information were approximately 50%. The reasons for patients' decision when they did not cite quantitative information were intriguing: among those who consented the most frequent reason was that they preferred "new things" or were willing to "try anything for relief"; among those declining to consent frequent responses included that they did not like the idea of an "experiment" or the usual medication seemed "safer or better." We predicted that the association between severity of symptoms would be linear--sick patients would be more likely to consent. However, the empirical design using real decisions casts doubt on our original supposition--the association was U-shaped! Patients perceiving themselves as having minimal or severe symptoms were less likely to consent than those whose symptom severity fell in the middle as assessed by a visual analog severity scale. This finding does not support the often held notion that only sick patients consent because they perceive their options to be limited. The skeptical reader may conclude that our experiment was too simple and that perhaps the outcomes were predictable. That is exactly the point! The information in the consent form was simple and succinct. Subjects had the
323
Clinical Trials of Informed Consent Table I
Interaction Between Consent Form and Citation of Quantitative Information on Consent Rate
Cited Quantitative Information Yes
No
Consent
Consent/ /
Form A
16 Consent
J Decline Consent/ / C°nSet ~
Form
Form B
12
~e;ne Source:
Reprinted from Ref. 3.
opportunity to discuss the trial with the physician and ask any question they desired. Unlike research using hypothetical scenarios, these patients were making a decision that they believed would lead to action. The results support the notion that patients will actually use the simple quantitative information provided during the informed consent process to make their decision. The results also have implications for improving the currently complex and comprehensive informed consent process. Others have also been interested in the results of our trial and emphasized that the quantitative information "played a powerful part in preference," suggesting that investigators dwell too much on the potential risks and should be more open about quantitatively discussing the potential benefits [4]. We strongly agree and believe that the emphasis in informed consent discussions tends to be unbalanced with potential risks provided more emphasis than potential benefits. There needs to be an appropriate balance between the detail needed to inform the patient and the verbal clutter that camouflages the message. Clinical trialists might identify at least two major concerns with any proposal to emphasize quantitatively the benefits and risks in a more balanced
324
D.L. Simel and J.R. Feussner discussion. First, investigators m a y c o n t e n d that information about efficacy is not k n o w n , which is w h y the trial is being p e r f o r m e d in the first place. H o w e v e r , some information must be k n o w n , otherwise sample size estimates could not be determined. Estimating the expected efficacy of a test treatment is i m p o r t a n t w h e n assessing the feasibility and validity of the s t u d y design. W h y not also make the estimates of efficacy an i m p o r t a n t part of the informed consent? Second, some might be c o n c e r n e d that a possibly biased investigator w o u l d overstate the expected efficacy. This is a valid concern that only underscores and reinforces the importance and responsibility of i n d e p e n d e n t institutional review boards and h u m a n ethics committees. We believe the question of the efficacy of informed consent m u s t be exa m i n e d not to ascertain w h e t h e r it works but to d e t e r m i n e h o w to make it w o r k better. An empirical a p p r o a c h can be used to s t u d y d e m o g r a p h i c and clinical factors that affect consent such as age, sex, race, severity of s y m p t o m s , general health status, or patient location (emergency ward, inpatient ward, intensive care unit, psychiatry clinic, etc.). Empirical research should allow us to u n d e r s t a n d the impact of alternative informed consent formats on outcomes such as consent rate, rates of d r o p o u t , or f r e q u e n c y of adverse effects. In ongoing trials, several alternative consent forms could be used at different periods during patient accession to d e t e r m i n e what effect varying the inf o r m e d consent formats might have on a decision to participate or refuse. For example, during different periods of an ongoing trials a traditional consent form could be c o m p a r e d to a simplified form that has quantitative tabular displays of anticipated benefits and risks. To address some of these issues, we have several r e c o m m e n d a t i o n s . First, we urge other clinical trialists to evaluate the informed consent process with appropriate well-designed studies. Second, we suggest that i n f o r m e d consent forms should be m a d e more succinct and contain quantitative information. Third, the presentation of potential benefits and risks should be more balanced to truly inform patients and not o v e r w h e l m , intimidate, or frighten them. Finally, if for no reason than to begin a dialogue b e t w e e n investigator and patient, we suggest that investigators ask patients w h y they chose to participate or refuse. A n y t h i n g we can do to make consent forms simpler and more succinct should help patients make more i n f o r m e d choices. Certainly this is a laudable goal and as clinical trialists these are issues we should w a n t to pursue.
REFERENCES
1. Mazur DJ: Why the goals of informed consent are not realized. J Gen Intern Med 3:370-380, 1988 2. Meisel A, Roth LH: What we do and do not know about informed consent. JAMA 246:2473-2477, 1981 3. Simel DL, Feussner JR: A randomized controlled trial comparing quantitative informed consent formats. J Clin Epidemiol 44:771-777, 1991 4. Informed consent: How informed? (Editorial) Lancet 338:665-666, 1991
Informed consent is a tenet of clinical care and clinical research that has been accepted by many without proof that the process works. Informed consent seems ethically correct. We recognize our moral obligation to tell patients about the treatment plan, intended benefits, possible side effects, and alternative therapies. Despite this moral imperative, some clinicians are discomfited by the informed consent process. They question whether informed consent is really "informed," whether patients consent freely or under duress caused by their illness; and they wonder whether informed consent is a mere legal obligation with little connection to the realities of medical treatment. These concerns are reasonable ones, but until recently they have been more a subject of debate rather than empirical research. As clinicians and clinical trialists, we have an obligation to approach empirically the issues of informed consent as rigorously as we approach the design, conduct, and analyses of trials themselves. This scientific approach to understanding the informed consent process will allow us to realize more fully the intended goals of informed consent [1]. We define empirical research on informed consent as the study of actual informed consent decisions by patients or their proxies with regard to consent, and the impact of consent on patients or clinical trial outcome. "Actual" consent decisions occur when patients believe they are making a real decision about treatment or participation in a clinical trial. This definition of empirical informed consent research should address some of the limitations that characterize previous research on informed consent as outlined by Meisel and Roth [2,3]. Some limitations include (1) use of nonpatient subjects or hypothetical situations, (2) failure to consider what physicians actually told the patient, (3) focusing only on patient recall as the key to understanding, (4) lack of generalizability, and (5) allowing investigator bias where the investigator was also the patient's physician. Research using hypothetical scenarios,
Address reprint requests to: David L. Simel, MD, MHS, Ambulatory Care, Department of Veterans Affairs Medical Center, 508 Fulton Street, Durham, NC 27705. Received December 10, 1991; revised March 11, 1992. Controlled Clinical Trials 13:321-324 (1992) © Elsevier Science Publishing Co., Inc. 1992 655 A v e n u e of the Americas, N e w York, N e w York 10010
321 0197-2456/92/$5.00
322
D.L. Sirnel and J.R. Feussner evaluating patient recall, or assessing only the patient's knowledge base after making their consent decision supplement empirical informed consent research, but such studies can not address the central issue of the patient's actual decision. We conducted a study of empirical informed consent to evaluate the impact of simple quantitative information on consent decisions [3]. We designed a sham trial in which randomized patients received one of two consent forms. One study (consent A) described a randomized trial of a new medication that may work "twice as fast as usual treatment," while the second (consent B) described a trial of a new medication that may work "half as fast as usual treatment." This experiment had several important design features that addressed some of the limitations of previous research: (1) we studied patients making real decisions; (2) we tape-recorded all patient-physician interactions and submitted them to an independent third party who documented that the presentations were unbiased and not coercive; (3) we did not confine our analysis to an assessment of patient recall; (4) we increased generalizability by studying patients with a variety of symptoms who presented to an urgentcare ambulatory clinic for evaluation; and (5) we decreased investigator bias by not having the patient's physician obtain the informed consent. Our a priori hypothesis had two components: (1) consent rates would be improved in an appropriate direction when patients did cite quantitative information as a factor, and (2) consent rates would be similar when patients did not cite quantitative information as a factor in their decision. Patients did not consent to the trials equally, and consent was strongly affected by the severity of their symptoms that led them to seek medical care. Patients who cited the quantitative information when they made their decision were highly likely to consent to study A (95% consented) and unlikely to consent to study B (64% did not consent; Table 1) [3]. Among patients who received consent A and cited quantitative information, 19/20 wanted a medicine that was twice as fast; among patients who received consent B and cited quantitative information, 14/16 declined because they wanted a faster medication. Consent rates for patients who did not cite quantitative information were approximately 50%. The reasons for patients' decision when they did not cite quantitative information were intriguing: among those who consented the most frequent reason was that they preferred "new things" or were willing to "try anything for relief"; among those declining to consent frequent responses included that they did not like the idea of an "experiment" or the usual medication seemed "safer or better." We predicted that the association between severity of symptoms would be linear--sick patients would be more likely to consent. However, the empirical design using real decisions casts doubt on our original supposition--the association was U-shaped! Patients perceiving themselves as having minimal or severe symptoms were less likely to consent than those whose symptom severity fell in the middle as assessed by a visual analog severity scale. This finding does not support the often held notion that only sick patients consent because they perceive their options to be limited. The skeptical reader may conclude that our experiment was too simple and that perhaps the outcomes were predictable. That is exactly the point! The information in the consent form was simple and succinct. Subjects had the
323
Clinical Trials of Informed Consent Table I
Interaction Between Consent Form and Citation of Quantitative Information on Consent Rate
Cited Quantitative Information Yes
No
Consent
Consent/ /
Form A
16 Consent
J Decline Consent/ / C°nSet ~
Form
Form B
12
~e;ne Source:
Reprinted from Ref. 3.
opportunity to discuss the trial with the physician and ask any question they desired. Unlike research using hypothetical scenarios, these patients were making a decision that they believed would lead to action. The results support the notion that patients will actually use the simple quantitative information provided during the informed consent process to make their decision. The results also have implications for improving the currently complex and comprehensive informed consent process. Others have also been interested in the results of our trial and emphasized that the quantitative information "played a powerful part in preference," suggesting that investigators dwell too much on the potential risks and should be more open about quantitatively discussing the potential benefits [4]. We strongly agree and believe that the emphasis in informed consent discussions tends to be unbalanced with potential risks provided more emphasis than potential benefits. There needs to be an appropriate balance between the detail needed to inform the patient and the verbal clutter that camouflages the message. Clinical trialists might identify at least two major concerns with any proposal to emphasize quantitatively the benefits and risks in a more balanced
324
D.L. Simel and J.R. Feussner discussion. First, investigators m a y c o n t e n d that information about efficacy is not k n o w n , which is w h y the trial is being p e r f o r m e d in the first place. H o w e v e r , some information must be k n o w n , otherwise sample size estimates could not be determined. Estimating the expected efficacy of a test treatment is i m p o r t a n t w h e n assessing the feasibility and validity of the s t u d y design. W h y not also make the estimates of efficacy an i m p o r t a n t part of the informed consent? Second, some might be c o n c e r n e d that a possibly biased investigator w o u l d overstate the expected efficacy. This is a valid concern that only underscores and reinforces the importance and responsibility of i n d e p e n d e n t institutional review boards and h u m a n ethics committees. We believe the question of the efficacy of informed consent m u s t be exa m i n e d not to ascertain w h e t h e r it works but to d e t e r m i n e h o w to make it w o r k better. An empirical a p p r o a c h can be used to s t u d y d e m o g r a p h i c and clinical factors that affect consent such as age, sex, race, severity of s y m p t o m s , general health status, or patient location (emergency ward, inpatient ward, intensive care unit, psychiatry clinic, etc.). Empirical research should allow us to u n d e r s t a n d the impact of alternative informed consent formats on outcomes such as consent rate, rates of d r o p o u t , or f r e q u e n c y of adverse effects. In ongoing trials, several alternative consent forms could be used at different periods during patient accession to d e t e r m i n e what effect varying the inf o r m e d consent formats might have on a decision to participate or refuse. For example, during different periods of an ongoing trials a traditional consent form could be c o m p a r e d to a simplified form that has quantitative tabular displays of anticipated benefits and risks. To address some of these issues, we have several r e c o m m e n d a t i o n s . First, we urge other clinical trialists to evaluate the informed consent process with appropriate well-designed studies. Second, we suggest that i n f o r m e d consent forms should be m a d e more succinct and contain quantitative information. Third, the presentation of potential benefits and risks should be more balanced to truly inform patients and not o v e r w h e l m , intimidate, or frighten them. Finally, if for no reason than to begin a dialogue b e t w e e n investigator and patient, we suggest that investigators ask patients w h y they chose to participate or refuse. A n y t h i n g we can do to make consent forms simpler and more succinct should help patients make more i n f o r m e d choices. Certainly this is a laudable goal and as clinical trialists these are issues we should w a n t to pursue.
REFERENCES
1. Mazur DJ: Why the goals of informed consent are not realized. J Gen Intern Med 3:370-380, 1988 2. Meisel A, Roth LH: What we do and do not know about informed consent. JAMA 246:2473-2477, 1981 3. Simel DL, Feussner JR: A randomized controlled trial comparing quantitative informed consent formats. J Clin Epidemiol 44:771-777, 1991 4. Informed consent: How informed? (Editorial) Lancet 338:665-666, 1991