Evidence-Based Guidelines for Migraine Headache: Overview of Program Description and Methodology

Transcription

1 Evidence-Based Guidelines for Migraine Headache: Overview of Program Description and Methodology Douglas C. McCrory, MD, MHSc Assistant Professor, Department of Medicine, Assistant Research Professor, Center for Clinical Health Policy Research, Duke University Medical Center, Durham, NC Research Associate, Center for Health Services Research in Primary Care Durham Veterans Affairs Medical Center, Durham, NC David B. Matchar, MD Professor of Medicine and Director, Center for Clinical Health Policy Research, Duke University Medical Center, Durham, NC Rebecca N. Gray, DPhil Center for Clinical Health Policy Research, Duke University Medical Center, Durham, NC Jay H. Rosenberg, MD, FAAN Department of Neurology, Southern California Permanente Medical Group, and Clinical Professor of Neurology, Voluntary Faculty, UCSD School of Medicine, San Diego, CA Stephen D. Silberstein, MD, FACP Professor of Neurology, Thomas Jefferson University, and Director of Jefferson Headache Center, Philadelphia, PA US Headache Consortium: American Academy of Family Physicians American Academy of Neurology American Headache Society American College of Emergency Physicians* American College of Physicians-American Society of Internal Medicine American Osteopathic Association National Headache Foundation The US Headache Consortium participants: J. Keith Campbell, MD; Frederick G. Freitag, DO; Benjamin Frishberg, MD; Thomas T. Gilbert, MD, MPH; David B. Matchar, MD; Douglas C. McCrory, MD, MHSc; Donald B. Penzien, PhD; Michael P. Pietrzak, MD, FACEP; Nabih M. Ramadan, MD; Jay H. Rosenberg, MD; Todd D. Rozen, MD; Stephen D. Silberstein, MD, FACP; Eric M. Wall, MD, MPH; William B. Young, MD. *Endorsement by ACEP means that ACEP agrees with the general concepts in the guidelines and believes that the developers have begun to define a process of care that considers the best interests of patients with migraine headache Copyright by the American Academy of Neurology: Licensed to the members of the US Headache Consortium 1

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3 Overview of Program Description and Methodology Background In June 1998, Duke University s Center for Clinical Health Policy Research (CCHPR), in collaboration with the American Academy of Neurology (AAN), completed a series of Technical Reviews on migraine sponsored by the Agency for Health Care Policy and Research (AHCPR) in Washington, DC. The AHCPR Technical Reviews systematically reviewed controlled trials of treatments for migraine published in English from 1966 through Four topics were covered: self-administered drug treatments for acute migraine (migraine is defined in Table 1); parenteral drug treatments for acute migraine; drug treatments for the prevention of migraine; and behavioral and physical treatments for migraine. 1-4 The Education and Research Foundation of the AAN later funded an additional report on diagnostic testing for headache patients, an update on sumatriptan and other 5-HT 1 agonists, and a report on butalbital-containing compounds for migraine and tension-type headache. These supplemental reviews employed the same methodology that was used in the original AHCPR Technical Reviews. A multidisciplinary panel was convened by a consortium of professional organizations to develop clinical practice guidelines in the primary care setting based on the reviews described above. The US Headache Consortium, as the panel was called, produced four guidelines, each related to a distinct set of management decisions: diagnostic testing (primarily neuroimaging studies), pharmacological management of acute attacks, migraine-preventive drugs, and behavioral and physical treatments for migraine. This article describes the methods used to 3

4 identify and synthesize evidence in the ACHPR Technical Reviews and to develop the clinical practice guidelines. Program Objective The objective of the US Headache Consortium was to develop scientifically sound, clinically relevant practice guidelines on headache, for use in the primary care setting. Practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. For the guidelines on chronic headache, these included diagnostic approach, acute and preventive pharmacologic treatment, and non-pharmacological measures. Methods used in the AHCPR Technical Reviews Treatment Reviews The following is a brief description of the methods used to prepare the AHCPR Technical Reviews that formed the basis for the US Headache Consortium s clinical practice guidelines on the treatment of migraine. Further details can be found in the methodology sections of the AHCPR Technical Reviews. 1-4 The reviews examined the effects of various treatments for migraine on headache pain and/or frequency. In the case of drug treatments, tolerability was also investigated. To be considered for inclusion, studies were required to be prospective, controlled trials of treatments for migraine (all medication treatment trials used only level one evidence which by definition also included blinding). Allocation to treatment groups had to be randomized or quasi-randomized 4

5 (i.e., based on some nonrandom process unrelated to the treatment selection or expected response). Concurrent cohort comparisons and other nonexperimental designs were excluded. Control groups could receive no intervention, placebo or (in the case of behavioral and physical treatments) sham intervention, usual care, or a specified alternative drug or nondrug treatment. Only trials conducted on adults and published in English were considered. Relevant controlled trials were identified through computerized searches of the MEDLINE, PsycINFO, and CINAHL databases, by searching the reference lists of review articles and included studies, by searching books on headache, and by consulting experts in the field. The search strategy used the MeSH term headache (exploded) and a published search strategy for identifying randomized controlled trials. 5 Identified citations were screened for inclusion based on specific criteria concerning patient population, intervention, study design, and type of outcome data reviewsed (see Table 2). Trials passing this screen were evaluated for methodological quality using the scale developed by Jadad and colleagues. 6 Data on study design, patient population, interventions, efficacy outcomes, and adverse events were abstracted onto specially designed forms. The efficacy outcomes analyzed and the methods of analysis used varied among reviews (see Table 2). In general, however, when outcomes were reported in dichotomous form, the reviewers required that the threshold for distinguishing between success and failure be clinically significant. For example, the reviewers interpreted a 50% or greater decrease in headache severity or frequency as meeting this criterion. Dichotomous data meeting this definition were used to calculate odds ratios. Outcomes reported on a continuous scale (e.g., mean headache severity or frequency scores) were used to calculate standardized mean differences or effect sizes whenever variance data were also reported. 5

6 In some cases, calculated efficacy measures yielded conclusions that were more conservative than those reached by the original investigators. This occurred most often when the original analyses used individual patient data (e.g., in trials using a crossover design or an ANOVA analysis) rather than comparisons of group means or proportions. In these cases, the original analyses were described in a narrative format, along with the reasons for the discrepancy from our results. Where similar trials provided data, meta-analysis of efficacy measures was performed. The identity and rates of adverse events were recorded and statistically compared. A summary in narrative format was used for additional data that met selection criteria but were not reported in sufficient detail to contribute to the quantitative synthesis. Diagnostic Review Investigators reviewed English-language studies published from 1966 through August 1998 that estimated the sensitivity, specificity, or predictive value of the clinical history, physical exam, or laboratory, radiological, or other tests for identifying significant intracranial abnormalities in patients presenting with nonacute headache. Studies that assessed observer variation or reproducibility of diagnostic tests for patients with nonacute headache were also included. Trials were identified through computerized searches of MEDLINE and by examining the reference lists of review articles, searching books on headache, and consulting experts in the field. The search paired a strategy that identified studies on the operating characteristics of diagnostic tests (modified from a strategy developed by the editorial staff of the Journal of the American Medical Association s Rational Clinical Examination Series ) 7 and a strategy that identified headachespecific terms. 6

7 Articles were included in the analysis if they provided original data for 20 or more subjects with nonacute headache and met at least one of the following criteria: compared clinical history, physical examination, laboratory, radiological, or other tests with a neuroimaging test as a reference standard. described the results of a neuroimaging study in a consecutive series or random sample of patients. For studies meeting these criteria, a general internist confirmed the relevance of each study, abstracted data from it, and assigned it a quality score. Study quality was graded using the methods accepted by the Journal of the American Medical Association s Rational Clinical Examination Series for methodological levels of evidence for grading diagnostic studies 7 (Table 3). Studies that did not address primary headache disorders, involved emergency patients only, or did not include enough data to perform analysis (e.g., did not provide the data necessary to construct a 2-by-2 table) were excluded. Studies were also excluded if the underlying cause of headache was known, if the study was performed in the acute treatment setting, or if the condition was a "new onset" headache. The analysis focused first on the effectiveness of the clinical evaluation (history and physical examination) for detecting intracranial anatomical abnormalities among patients presenting with nonacute headache in the primary care setting. The clinical evaluation of the patient was treated as a screening test that might predict abnormalities on imaging. Computerized tomography (CT) and magnetic resonance imaging (MRI) were treated as confirmatory gold standard or reference standard tests. With the assistance of two board-certified neurologists, the reviewers classified all the neuroimaging outcomes reported in the included studies as either significant abnormalities, 7

8 abnormalities possibly related to headache, insignificant abnormalities, or normal (see Table 4). The analysis focused exclusively on significant abnormalities. To describe the efficiency of the screening tests, sensitivity and specificity were combined to create likelihood ratios. The pretest odds of disease were multiplied by the likelihood ratio to calculate the post-test odds. Values greater than one increase the odds of disease, while values less than one diminish the odds, and values approaching one have an increasingly small impact on changing the odds of disease beyond the baseline prevalence. Confidence intervals were constructed around the likelihood ratios, assessing whether the 95% limits included or excluded the indeterminate value of one. For tests yielding continuous outcomes only, standard statistical methods were used to compare means between groups with and without significant abnormalities on neuroimaging. When several studies provided estimates of a single parameter, these estimates were tested for homogeneity. If studies were clinically and statistically homogeneous, a summary estimate was calculated using a fixed-effects meta-analysis. Peer Review of Technical Reviews All of the AHCPR Technical Reviews underwent an external peer review process and were modified to incorporate substantive and editorial changes suggested by reviewers. Methods used in Developing the Clinical Practice Guidelines: Assembly of the US Headache Consortium The AAN invited organizations whose constituents treat or represent headache patients, to nominate representatives to the US Headache Consortium. Seven organizations participated: the American Academy of Family Physicians, American Academy of Neurology, American 8

9 Headache Society, American College of Emergency Physicians, American College of Physicians, American Osteopathic Association, and National Headache Foundation. The multidisciplinary US Headache Consortium provided a balance of practicing generalist physicians, headache specialist physicians, and other health professionals from relevant disciplines, and was supported by individuals with expertise in administration, writing and editing, and in the methodology of evidence synthesis and guideline development. Values In formulating guideline recommendations, the US Headache Consortium considered data on relief of headache symptoms, functional status, quality of life, and tolerability of treatment. Cost of treatment was not explicitly considered in the guideline development process. The US Headache Consortium strove to base all of its recommendations on high-quality evidence. Only for compelling issues were recommendations made based on expert judgment. Consensus Development No formal or explicit techniques were used to reach consensus among members of the US Headache Consortium. Starting with the AHCPR Technical Reviews on a given topic, a subgroup of members prepared summary evidence tables, wrote narrative descriptions of the evidence, and formulated specific treatment recommendations. These guideline documents were reviewed and voted on by the entire US Headache Consortium. Recommendations required consensus, defined as unanimous agreement. Topics on which consensus could not be reached were described in the guidelines as areas of disagreement. Evidence not considered in the AHCPR Technical Reviews was incorporated if recommended by the US Headache Consortium; such data were reviewed and 9

10 graded for quality by the project methodologist. This evidence included studies published after the Technical Reviews were completed and studies on topics outside the scope of the AHCPR Technical Reviews. Grading Recommendations Recommendations were graded according to the level of evidence supporting them. The grading system adopted by the Consortium rates the aggregated evidence, including the number of studies and the consistency of their findings, thereby implicitly acknowledging that trials of the same treatment sometimes yield conflicting results. Recommendations in the Treatment Guidelines were graded according to the following scale, adapted from a previous AHCPR Guideline: 8 A. Multiple well-designed randomized clinical trials, directly relevant to the recommendation, yielded a consistent pattern of findings. B. Some evidence from randomized clinical trials supported the recommendation, but the scientific support was not optimal. For instance, few randomized trials existed, the trials that did exist were somewhat inconsistent, or the trials were not directly relevant to the recommendation. An example of the last point would be the case where trials were conducted using a study group that differed from the target group for the recommendation. C. The US Headache Consortium achieved consensus on the recommendation in the absence of relevant randomized controlled trials. This scale was adapted for recommendations about diagnostic testing as follows: 10

11 A. Multiple well-designed clinical studies, in cohorts of patients directly relevant to the recommendation, yielded a consistent pattern of findings. B. Some evidence from clinical studies in appropriate cohorts of patients supported the recommendation, but the scientific support was not optimal. For instance, either few studies existed or the studies that did exist were small or somewhat inconsistent. C. The US Headache Consortium achieved consensus on the recommendation in the absence of clinical studies or based on studies that were conducted using a study group that differed from the target group for the recommendation. Validation After approval by the US Headache Consortium members, Guideline drafts were reviewed by the appropriate representative of each of the Consortium s member organizations. None of these reviewers had been directly involved in the preparation of the Technical Reviews or Guideline recommendations. The US Headache Consortium responded to all comments from the reviewers, and revised versions of the Guidelines were resubmitted to each member organization s governing body for approval. The Guidelines have not been field-tested in clinical use. Acknowledgments The authors and US Headache Consortium wish to thank Starr Pearlman, PhD, and Joanne Okagaki for their help in preparing this manuscript and for their administrative support. We also wish to acknowledge the scientific advice of Drs. Jes Olesen, Jean Schoenen, Helene Massiou, Peer Tfelt Hansen, F. Cankat Tulunay, and Kai Jensen. 11

12 Funding and Support The Evidenced-Based Guidelines for Migraine Headache were supported by: Abbott Laboratories, AstraZeneca, Bristol Myers Squibb, Glaxo Wellcome, Merck, Pfizer, Ortho-McNeil and the AAN Education & Research Foundation, along with the seven participant member organizations. 12

13 References 1. Gray RN, McCrory DC, Eberlein K, Westman EC, Hasselblad V. Self-Administered Drug Treatments for Acute Migraine Headache. Technical Review, 2.4. February (Prepared for the Agency for Health Care Policy and Research under Contract No Available from the National Technical Information Service; NTIS Accession No ) 2. Gray RN, McCrory DC, Eberlein K, Westman EC, Hasselblad V. Parenteral Drug Treatments for Acute Migraine Headache. Technical Review, 2.5 February (Prepared for the Agency for Health Care Policy and Research under Contract No Available from the National Technical Information Service; NTIS Accession No ) 3. Gray RN, Goslin RE, McCrory DC, Eberlein K, Tulsky J, Hasselblad V. Drug Treatments for the Prevention of Migraine Headache. Technical Review, 2.3. February (Prepared for the Agency for Health Care Policy and Research under Contract No Available from the National Technical Information Service; NTIS Accession No ) 4. Goslin RE, Gray RN, McCrory DC, Penzien D, Rains J, Hasselblad V. Behavioral and Physical Treatments for Migraine Headache. Technical Review, 2.2. February (Prepared for the Agency for Health Care Policy and Research under Contract No Available from the National Technical Information Service; NTIS Accession No ) 5. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. Br Med J. 1994;309(6964): Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clin Trials. 1996;117(1): Holleman DR, Simel DL. Does the clinical examination predict pulmonary airflow obstruction? JAMA. 1995;273: Fiore MC, Bailey WC, Cohen SJ, et al. Smoking Cessation. Clinical Practice Guideline No 18. Rockville, MD: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. AHCPR Publication No April Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias, and facial pain. Cephalalgia. 1988;8(suppl 7):

14 Table 1 International Headache Society (HIS) diagnostic criteria for migraine without and with aura Migraine without aura: A. At least 5 attacks fulfilling B-D. B. Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated). C. Headache has a least two of the following characteristics: 1. Unilateral location 2. Pulsating quality 3. Moderate or severe intensity (inhibits or prohibits daily activities) 4. Aggravation by walking stairs or similar routine physical activity D. During headache at least one of the following: 1. Nausea and/or vomiting 2. Photophobia and phonophobia E. At least one of the following: 1. History, physical- and neurological examinations do not suggest one of the disorders listed in groups History, physical- and/or neurological examination do suggest such disorder, but it is ruled out by appropriate investigations 3. Such disorder is present, but migraine attacks do not occur for the first time in close temporal relation to the disorder 1.2 Migraine with aura: A. At least 2 attacks fulfilling B B. At least 3 of the following 4 characteristics: 1. One or more fully reversible aura symptoms indicating focal cerebral cortical - and/or brain stem dysfunction 2. At least one aura symptom develops gradually over more than 4 minutes or, 2 or more symptoms occur in succession 3. No aura symptom lasts more than 60 minutes. If more than one aura symptom is present, accepted duration is proportionally increased 4. Headache follows aura with a free interval of less than 60 minutes. (It may also begin before or simultaneously with the aura) C. At least one of the following 1. History, physical- and neurological examination do not suggest one of the disorders listed in groups History and/or physician and/or neurological examination do suggest such disorder, but it is ruled out by appropriate investigations 3. Such disorder is present, but migraine attacks do not occur for the first time in close temporal relation to the disorder * In children below age 15, attacks may last 2-48 hours. If the patient falls asleep and wakes up without migraine, duration of attack is until time awakening. 14

15 Table 2: Important characteristics of AHCPR Technical Reviews on migraine diagnosis and treatment Patient population Intervention Diagnostic Patients presenting with nonacute headache in primary care setting Data from history and physical examination (including neurological exam) or from laboratory, radiographic, or other studies (e.g., EEG) Study design Studies correlating historical, physical exam, or laboratory findings to reference standard test (CT or MRI); must be able to construct 2-by-2 table Quality assessment 4-point scale developed by Holleman and Simel (1995) Acute (including Preventive Behavioral/ parenteral) Physical Adults with migraine Adults with migraine Adults with migraine Active: Drug treatments aimed at the relief of symptoms of individual episodes of migraine Control: Placebo, no intervention, usual care, or a specified alternative drug or nondrug treatment Prospective, controlled trials; allocation to treatment randomized or quasi-randomized 5-point scale developed by Jadad, Moore, Carroll, et al. (1996) Active: Drug treatments taken regularly during headache-free intervals and intended to prevent the occurrence of episodes of migraine Control: Placebo, no intervention, usual care, or a specified alternative drug or nondrug treatment Prospective, controlled trials; allocation to treatment randomized or quasirandomized 5-point scale developed by Jadad, Moore, Carroll, et al. (1996) Active: Behavioral or physical treatments aimed at the prevention of attacks of migraine or the relief of symptoms of individual attacks Control: No intervention, placebo or sham intervention, usual care, or a specified alternative drug or nondrug treatment Prospective, controlled trials; allocation to treatment randomized or quasi-randomized 5-point scale developed by Jadad, Moore, Carroll, et al. (1996) 15

16 Outcomes data Identification of significant intracranial abnormalities Preferred efficacy outcomes (in descending order): (1) headache relief or change in headache intensity; (2) post-treatment headache intensity; (3) functional disability or headache duration Preferred efficacy outcomes (in descending order): (1) headache index; (2) headache frequency; (3) headache intensity Data obtained directly from patient and recorded daily (e.g., in headache diary) Preferred efficacy outcomes (in descending order): (1) headache index; (2) headache frequency; (3) headache intensity Data obtained directly from patient and recorded daily (e.g., in headache diary) Data obtained directly from patient Outcomes analyzed at 1-2 hours Adverse event data recorded Outcomes analyzed posttreatment (8-12 wks or immediately after treatment, whichever was later); follow-up (last available time point for which dropout rate was < 20%, with data reported for all groups) Outcomes analyzed posttreatment (8-12 wks or immediately after treatment, whichever was later); follow-up (last available time point for which dropout rate was < 20%, with data reported for all groups) Summary efficacy measures Likelihood ratio positive, likelihood ratio negative Odds ratio (dichotomous) or effect size (continuous) Adverse event data recorded Odds ratio (dichotomous) or effect size (continuous) Odds ratio (dichotomous) or effect size (continuous) 16

17 Table 3: Scale for grading quality of diagnostic studies 7 Level I evidence: Independent, blind comparison with a gold standard of anatomy, physiology, diagnosis, or prognosis among a large number of consecutive patients suspected of having the target condition. Independent: Neither the test result nor the gold standard result was used to select patients for the study. Blind: Test and gold standard each applied and interpreted without knowledge of the result of the other. Gold standard: The results of biopsy, angiography, autopsy, plain radiographs, sonogram, physiological study, follow-up, therapeutic response, etc., that established the true anatomy, physiology, diagnosis, or outcome of the target condition. Target condition: The anatomical or physiological state, disease, syndrome, prognosis, or therapeutic response that the sign or symptom identifies. Large number: Sufficient numbers of patients to have narrow confidence limits on the resulting sensitivity, specificity, or likelihood ratio. Level II evidence: Independent, blind comparison with a gold standard among a small number of consecutive patients suspected of having the target condition. Small number: Insufficient numbers of patients to have narrow confidence limits on the resulting sensitivity, specificity, or likelihood ratio. Level III evidence: Independent, blind comparison with a gold standard among nonconsecutive patients suspected of having the target condition. Level IV evidence: Included studies which did not meet criteria for at least Level III evidence. 17

18 Table 4: Classification of abnormalities found on neuroimaging Classification of abnormalities Significant abnormalities Abnormalities possibly related to headache Insignificant abnormalities Definition Related to headache and requiring definite action. Examples include acute cerebral infarct, acute cerebral edema, acute cerebral hemorrhage (subarachnoid, intra-parenchymal, or extraaxial), neoplastic disease, hydrocephalus, and vascular abnormalities (e.g., aneurysm or arteriovenous malformation). Possibly related to headache; may require definite action. Examples include metastases to the calvarium, acute or chronic sinusitis, and abnormalities of the nasal cavity. Unrelated to headache or requiring no action. Examples include developmental venous anomaly, cerebral or cerebellar atrophy, subcortical (lacunar) infarction, old cortical infarction, and normal variants (e.g., cavum septum pellucidum, physiological calcifications). 18