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ethnicity in epilepsy clinical trials
Epilepsy & Behavior Epilepsy & Behavior 5 (2004) 743–745 www.elsevier.com/locate/yebeh
Reporting race/ethnicity in epilepsy clinical trials Jorge G. Burneoa,* and Roy Martinb a
Epilepsy Programme, London Health Sciences Center, University of Western Ontario, London, Ont., N5X 2Y6 Canada b Epilepsy Center, University of Alabama at Birmingham, Birmingham, AL, USA Received 13 April 2004; revised 27 May 2004; accepted 27 May 2004 Available online 2 July 2004
Abstract The increasing necessity to address and answer questions regarding disparities in epilepsy among different racial/ethnic groups is not being fulfilled. The present study found that only 6.6% of clinical trials in epilepsy reported the race/ethnicity of study participants, and only 1.9% did try to analyze possible differences between them. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Race; Ethnicity; Epilepsy; Clinical trials
1. Introduction There is more need in daily clinical practice to answer questions regarding health disparities among racial and ethnic groups. Investigators, clinicians, and educators are looking into the scientific literature for guidance on addressing health disparities. The National Institutes of Health now requires that investigators carrying out clinical research demonstrate adequate representation of minorities and diverse ethnic groups in study samples to examine epidemiological characteristics, diverse diagnostic tests, and differential effects of various therapies [1–4]. There is a need for representation of minorities in clinical research, especially in diseases where known disparities in health exist; in this way we can change our clinical practice so their necessities can be addressed [2–4]. Epilepsy is a public health problem affecting around 50 million people worldwide [5]. It is the most common serious neurological condition, with an incidence of 50– 70 in 100,000 people in industrialized countries and between 100 and 190 per 100,000 in developing countries [6,7].
* Corresponding author. Fax: 1-519-663-3753. E-mail address: [email protected] (J.G. Burneo).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.05.010
The main aim of this study was to examine, in highimpact journals specialized in the areas of neurology and epilepsy, the reporting of race/ethnicity in clinical trials in epilepsy and to determine what factors were associated with reporting of race/ethnicity. Whether analyses by race/ethnicity were described in these reports was also examined.
2. Methods A bibliographic search covering the period from January 2000 to January 2004 was performed to identify publications in the following major journals on neurology and epilepsy in the United States: Neurology, Annals of Neurology, Archives of Neurology, Epilepsy & Behavior, and Epilepsia. The journals were chosen because primary reports of clinical trials published in these journals have a large impact on the U.S. neurologist and epileptologist audience due to their high readership. Editorials, letters, meta-analyses, secondary analyses of study samples from clinical trials, and clinical trials conducted with patients outside the United States were excluded. Original articles, including clinical randomized, as well as retrospective and prospective, open-label, observational studies were included. The search engine for each particular journal in the web was employed when possible, using the keywords
744
J.G. Burneo, R. Martin / Epilepsy & Behavior 5 (2004) 743–745
seizure and epilepsy separately. If not, each paper version issue of these journals was reviewed.
3. Collection of data and analysis For each clinical trial, data from tables or the results sections on race/ethnicity of participants, as well as how race/ethnicity was classified, were collected. Year of publication, funding sources, whether the authors explicitly stated exclusion of any race or ethnicity, and whether authors reported oversampling of minorities were collected. Whether any analysis was conducted by race/ethnicity, as mentioned in the methods, results, or discussion section, was determined.
4. Results A total of 318 studies were included. The trials included 160,150 study participants, with sample sizes ranging from 5 to 80,682 (mean ¼ 497, median ¼ 41). In more than half of the trials (n ¼ 176), mean age was reported and ranged from 2.8 to 73.5 years. None of the trials were classified as race-focused. Of the 318 studies reviewed, only 6.6% (n ¼ 21) reported the race/ethnicity of study participants (Table 1). Of studies reporting race/ethnicity, 19% reported only two racial/ethnic categories. Among the non-race-focused trials reporting race/ethnicity, 10 included three or more racial/ethnic groups, with one of these groups being classified as ‘‘others’’ in most of the studies. Only one study included the ‘‘more than one racial group’’ category. Although 6.6% of the examined trials reported race/ ethnicity categories, 71% of them did not analyze possible differences between these groups.
5. Discussion The findings of this study indicate that results according to race and ethnicity are almost never described Table 1 Reporting and analysis of results by race/ethnicity in published clinical trials
Non-race-focused trials reporting categories of race/ethnicity among participants Two categories Three categories Four categories Five categories Six categories Number of trials reporting analyses by race
N
%
21
6.6
4 6 6 3 1 6
1.9
in epilepsy clinical trials. Although federal mandates may have increased the participation of minority groups in clinical research, that inclusion has not translated into reporting of results and has not translated into the performance of clinical studies that might guide not only therapeutic, but also all general clinical decisions. It is well known from different studies that there are some racial/ethnic disparities, not only in response to treatment, but also in the way individuals clinically present and at the molecular level, in diseases like hypertension, diabetes, and cancer [8–10]. This knowledge has allowed physicians in different specialties to offer better care to patients in different racial/ethnic groups. An explanation for our findings may be that there is not parity in trial participation by the different racial/ ethnic groups. Even though that is not the case in other diseases like cancer [10], less access to epilepsy studies and probably studies of other neurological conditions among minorities, as well as declining participation of minority subjects in trials of drug products approved by the Food and Drug Administration like antiepileptic medications, may be the case. Another explanation may be that investigators include minority subjects but do not perform or are reluctant to do subgroup analysis. This may be because these analyses were not planned in advance and, therefore, do not have adequate power to show a statistical difference and, also, because of the controversies that subgroup analysis may generate, particularly when it is done with the purpose of evaluating differences between racial/ethnic groups [11]. Lack of reporting of negative results, because these were not statistically significant, and lack of formal guidelines in different medical journals on reporting race/ethnicity may be additional explanations for the findings. Another important issue is the existence of a great number of studies in which race/ethnicity is not even mentioned, probably because it is thought that different racial/ethnic groups do not differ with respect to the various aspects of epilepsy, something that has not been completely demonstrated. Some of the studies included only two different racial/ ethnic groups (blacks and whites). This may indicate that the investigator probably reported only the proportion of individuals who where classified as black or white in a sample that may have comprised other racial and ethnic groups. Reports including more than two groups would be more accurate. In only one study the authors included a group defined as ‘‘more than one race was chosen,’’ because in that particular study, patients defined their racial/ethnic backgrounds themselves, a practice that is gaining greater acceptance in the medical research community [12]. One of the main limitations of this study may be the fact that the journals reviewed here may not be repre-
J.G. Burneo, R. Martin / Epilepsy & Behavior 5 (2004) 743–745
sentative of what a physician taking care of patients with epilepsy reads, as it is known that many patients with epilepsy are being cared for by primary practitioners (internal medicine, family practice, between other specialties), and they do not read neurological journals. The present study did not intend to extensively review the importance of race and ethnicity in the outcome of clinical trials, like the effects at both the molecular level and with differences in clinical presentation, nor was it intended to address major issues in differential drug response in different ethnic groups (differences in drug metabolism secondary to pharmacogenetic differences). The present study described the reporting of race/ethnicity in clinical trials in epilepsy and discussed the possible factors associated with it. Development of clinical trials aimed at assessing potential differential treatment response should be one goal of future outcome studies. At the present time clinical trial data are not sufficient to make any meaningful comments. Over the past two decades, the U.S. population has become more diverse, and geographic areas that were exclusively white or black are becoming multiethnic [13]. The needs of these emerging ethnic groups are different and, in some cases, challenging to physicians who are currently looking for evidence from different sources, which are always directly or indirectly linked to information provided by respected journals in the field of concern. The lack of description of race/ethnicity in epilepsy clinical trials, as well as the need for studies designed to assess differential responses related to race/ethnicity, warrants more critical attention, not only because different funding agencies, especially the National Institutes of Health, mandate such information inclusion, but because it is very important to know if potential differences exist, so that the needs of people with epi-
745
lepsy can be addressed and they can be offered better evidence-based care.
References [1] National Institutes of Health Revitalization Act of 1993. [2] National Institutes of Health, Department of Health and Human Services, NIH guidelines on the inclusion of women and minorities as subjects in clinical research. Fed Regist 1994;59:14508–13. [3] Freedman LS, Simon R, Foulkes MA, et al. Inclusion of women and minorities in clinical trials and the NIH revitalization act of 1993: the perspective of NIH clinical trialists. Control Clin Trials 1995;16:277–85. [4] Hohmann AA, Parron DL. How the new BIH guidelines on inclusion of women and minorities apply: efficacy trials, efectiveness trials, and validity. J Consult Clin Psychol 1996;64:851–5. [5] Brodie MJ, Schachter SC. Epilepsy. Oxford: Health Press; 2000. [6] Sander JW, Shorvon SD. Incidence and prevalence studies in epilepsy and their methodological problems: a review. J Neurol Neurosurg Psychiatry 1987;50:829–39. [7] Sander JW, Shorvon SD. Epidemiology of the epilepsies. J Neurol Neurosurg Psychiatry 1996;61:433–43 (published erratum appears in J Neurol Neurosurg Psychiatry 1997; 62:679). [8] Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003;289:2560–71. [9] Cox RH, Carpenter JP, Bruce FA, et al. Characteristics of lowincome African-American and Caucasian adults that are important in self-management of type 2 diabetes. J Community Health 2004;29:155–70. [10] Tejeda HA, Green SB, Trimble EL, et al. Representation of African-Americans, Hispanics, and whites in National Cancer Institute cancer treatment trials. J Natl Cancer Inst 1996;88:812–6. [11] Schwartz RS. Racial profiling in medical research. N Engl J Med 2001;344:1392–3. [12] Ethnicity, race and culture: guidelines for research, audit and publication. BMJ 1996;312:1094. [13] 2000 U.S. Census Data. Available at: http://factfinder.census.gov. Accessed April 3rd, 2004.
Reporting race/ethnicity in epilepsy clinical trials Jorge G. Burneoa,* and Roy Martinb a
Epilepsy Programme, London Health Sciences Center, University of Western Ontario, London, Ont., N5X 2Y6 Canada b Epilepsy Center, University of Alabama at Birmingham, Birmingham, AL, USA Received 13 April 2004; revised 27 May 2004; accepted 27 May 2004 Available online 2 July 2004
Abstract The increasing necessity to address and answer questions regarding disparities in epilepsy among different racial/ethnic groups is not being fulfilled. The present study found that only 6.6% of clinical trials in epilepsy reported the race/ethnicity of study participants, and only 1.9% did try to analyze possible differences between them. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Race; Ethnicity; Epilepsy; Clinical trials
1. Introduction There is more need in daily clinical practice to answer questions regarding health disparities among racial and ethnic groups. Investigators, clinicians, and educators are looking into the scientific literature for guidance on addressing health disparities. The National Institutes of Health now requires that investigators carrying out clinical research demonstrate adequate representation of minorities and diverse ethnic groups in study samples to examine epidemiological characteristics, diverse diagnostic tests, and differential effects of various therapies [1–4]. There is a need for representation of minorities in clinical research, especially in diseases where known disparities in health exist; in this way we can change our clinical practice so their necessities can be addressed [2–4]. Epilepsy is a public health problem affecting around 50 million people worldwide [5]. It is the most common serious neurological condition, with an incidence of 50– 70 in 100,000 people in industrialized countries and between 100 and 190 per 100,000 in developing countries [6,7].
* Corresponding author. Fax: 1-519-663-3753. E-mail address: [email protected] (J.G. Burneo).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.05.010
The main aim of this study was to examine, in highimpact journals specialized in the areas of neurology and epilepsy, the reporting of race/ethnicity in clinical trials in epilepsy and to determine what factors were associated with reporting of race/ethnicity. Whether analyses by race/ethnicity were described in these reports was also examined.
2. Methods A bibliographic search covering the period from January 2000 to January 2004 was performed to identify publications in the following major journals on neurology and epilepsy in the United States: Neurology, Annals of Neurology, Archives of Neurology, Epilepsy & Behavior, and Epilepsia. The journals were chosen because primary reports of clinical trials published in these journals have a large impact on the U.S. neurologist and epileptologist audience due to their high readership. Editorials, letters, meta-analyses, secondary analyses of study samples from clinical trials, and clinical trials conducted with patients outside the United States were excluded. Original articles, including clinical randomized, as well as retrospective and prospective, open-label, observational studies were included. The search engine for each particular journal in the web was employed when possible, using the keywords
744
J.G. Burneo, R. Martin / Epilepsy & Behavior 5 (2004) 743–745
seizure and epilepsy separately. If not, each paper version issue of these journals was reviewed.
3. Collection of data and analysis For each clinical trial, data from tables or the results sections on race/ethnicity of participants, as well as how race/ethnicity was classified, were collected. Year of publication, funding sources, whether the authors explicitly stated exclusion of any race or ethnicity, and whether authors reported oversampling of minorities were collected. Whether any analysis was conducted by race/ethnicity, as mentioned in the methods, results, or discussion section, was determined.
4. Results A total of 318 studies were included. The trials included 160,150 study participants, with sample sizes ranging from 5 to 80,682 (mean ¼ 497, median ¼ 41). In more than half of the trials (n ¼ 176), mean age was reported and ranged from 2.8 to 73.5 years. None of the trials were classified as race-focused. Of the 318 studies reviewed, only 6.6% (n ¼ 21) reported the race/ethnicity of study participants (Table 1). Of studies reporting race/ethnicity, 19% reported only two racial/ethnic categories. Among the non-race-focused trials reporting race/ethnicity, 10 included three or more racial/ethnic groups, with one of these groups being classified as ‘‘others’’ in most of the studies. Only one study included the ‘‘more than one racial group’’ category. Although 6.6% of the examined trials reported race/ ethnicity categories, 71% of them did not analyze possible differences between these groups.
5. Discussion The findings of this study indicate that results according to race and ethnicity are almost never described Table 1 Reporting and analysis of results by race/ethnicity in published clinical trials
Non-race-focused trials reporting categories of race/ethnicity among participants Two categories Three categories Four categories Five categories Six categories Number of trials reporting analyses by race
N
%
21
6.6
4 6 6 3 1 6
1.9
in epilepsy clinical trials. Although federal mandates may have increased the participation of minority groups in clinical research, that inclusion has not translated into reporting of results and has not translated into the performance of clinical studies that might guide not only therapeutic, but also all general clinical decisions. It is well known from different studies that there are some racial/ethnic disparities, not only in response to treatment, but also in the way individuals clinically present and at the molecular level, in diseases like hypertension, diabetes, and cancer [8–10]. This knowledge has allowed physicians in different specialties to offer better care to patients in different racial/ethnic groups. An explanation for our findings may be that there is not parity in trial participation by the different racial/ ethnic groups. Even though that is not the case in other diseases like cancer [10], less access to epilepsy studies and probably studies of other neurological conditions among minorities, as well as declining participation of minority subjects in trials of drug products approved by the Food and Drug Administration like antiepileptic medications, may be the case. Another explanation may be that investigators include minority subjects but do not perform or are reluctant to do subgroup analysis. This may be because these analyses were not planned in advance and, therefore, do not have adequate power to show a statistical difference and, also, because of the controversies that subgroup analysis may generate, particularly when it is done with the purpose of evaluating differences between racial/ethnic groups [11]. Lack of reporting of negative results, because these were not statistically significant, and lack of formal guidelines in different medical journals on reporting race/ethnicity may be additional explanations for the findings. Another important issue is the existence of a great number of studies in which race/ethnicity is not even mentioned, probably because it is thought that different racial/ethnic groups do not differ with respect to the various aspects of epilepsy, something that has not been completely demonstrated. Some of the studies included only two different racial/ ethnic groups (blacks and whites). This may indicate that the investigator probably reported only the proportion of individuals who where classified as black or white in a sample that may have comprised other racial and ethnic groups. Reports including more than two groups would be more accurate. In only one study the authors included a group defined as ‘‘more than one race was chosen,’’ because in that particular study, patients defined their racial/ethnic backgrounds themselves, a practice that is gaining greater acceptance in the medical research community [12]. One of the main limitations of this study may be the fact that the journals reviewed here may not be repre-
J.G. Burneo, R. Martin / Epilepsy & Behavior 5 (2004) 743–745
sentative of what a physician taking care of patients with epilepsy reads, as it is known that many patients with epilepsy are being cared for by primary practitioners (internal medicine, family practice, between other specialties), and they do not read neurological journals. The present study did not intend to extensively review the importance of race and ethnicity in the outcome of clinical trials, like the effects at both the molecular level and with differences in clinical presentation, nor was it intended to address major issues in differential drug response in different ethnic groups (differences in drug metabolism secondary to pharmacogenetic differences). The present study described the reporting of race/ethnicity in clinical trials in epilepsy and discussed the possible factors associated with it. Development of clinical trials aimed at assessing potential differential treatment response should be one goal of future outcome studies. At the present time clinical trial data are not sufficient to make any meaningful comments. Over the past two decades, the U.S. population has become more diverse, and geographic areas that were exclusively white or black are becoming multiethnic [13]. The needs of these emerging ethnic groups are different and, in some cases, challenging to physicians who are currently looking for evidence from different sources, which are always directly or indirectly linked to information provided by respected journals in the field of concern. The lack of description of race/ethnicity in epilepsy clinical trials, as well as the need for studies designed to assess differential responses related to race/ethnicity, warrants more critical attention, not only because different funding agencies, especially the National Institutes of Health, mandate such information inclusion, but because it is very important to know if potential differences exist, so that the needs of people with epi-
745
lepsy can be addressed and they can be offered better evidence-based care.
References [1] National Institutes of Health Revitalization Act of 1993. [2] National Institutes of Health, Department of Health and Human Services, NIH guidelines on the inclusion of women and minorities as subjects in clinical research. Fed Regist 1994;59:14508–13. [3] Freedman LS, Simon R, Foulkes MA, et al. Inclusion of women and minorities in clinical trials and the NIH revitalization act of 1993: the perspective of NIH clinical trialists. Control Clin Trials 1995;16:277–85. [4] Hohmann AA, Parron DL. How the new BIH guidelines on inclusion of women and minorities apply: efficacy trials, efectiveness trials, and validity. J Consult Clin Psychol 1996;64:851–5. [5] Brodie MJ, Schachter SC. Epilepsy. Oxford: Health Press; 2000. [6] Sander JW, Shorvon SD. Incidence and prevalence studies in epilepsy and their methodological problems: a review. J Neurol Neurosurg Psychiatry 1987;50:829–39. [7] Sander JW, Shorvon SD. Epidemiology of the epilepsies. J Neurol Neurosurg Psychiatry 1996;61:433–43 (published erratum appears in J Neurol Neurosurg Psychiatry 1997; 62:679). [8] Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003;289:2560–71. [9] Cox RH, Carpenter JP, Bruce FA, et al. Characteristics of lowincome African-American and Caucasian adults that are important in self-management of type 2 diabetes. J Community Health 2004;29:155–70. [10] Tejeda HA, Green SB, Trimble EL, et al. Representation of African-Americans, Hispanics, and whites in National Cancer Institute cancer treatment trials. J Natl Cancer Inst 1996;88:812–6. [11] Schwartz RS. Racial profiling in medical research. N Engl J Med 2001;344:1392–3. [12] Ethnicity, race and culture: guidelines for research, audit and publication. BMJ 1996;312:1094. [13] 2000 U.S. Census Data. Available at: http://factfinder.census.gov. Accessed April 3rd, 2004.