Amy Kendrick

Effect of Clinical Decision-Support Systems: A Systematic Review

BACKGROUND Despite increasing emphasis on the role of clinical decision-support systems (CDSSs) for improving care and reducing costs, evidence to support widespread use is lacking. PURPOSE To evaluate the effect of CDSSs on clinical outcomes, health care processes, workload and efficiency, patient satisfaction, cost, and provider use and implementation. DATA SOURCES MEDLINE, CINAHL, PsycINFO, and Web of Science through January 2011. STUDY SELECTION Investigators independently screened reports to identify randomized trials published in English of electronic CDSSs that were implemented in clinical settings; used by providers to aid decision making at the point of care; and reported clinical, health care process, workload, relationship-centered, economic, or provider use outcomes. DATA EXTRACTION Investigators extracted data about study design, participant characteristics, interventions, outcomes, and quality. DATA SYNTHESIS 148 randomized, controlled trials were included. A total of 128 (86%) assessed health care process measures, 29 (20%) assessed clinical outcomes, and 22 (15%) measured costs. Both commercially and locally developed CDSSs improved health care process measures related to performing preventive services (n= 25; odds ratio [OR], 1.42 [95% CI, 1.27 to 1.58]), ordering clinical studies (n= 20; OR, 1.72 [CI, 1.47 to 2.00]), and prescribing therapies (n= 46; OR, 1.57 [CI, 1.35 to 1.82]). Few studies measured potential unintended consequences or adverse effects. LIMITATIONS Studies were heterogeneous in interventions, populations, settings, and outcomes. Publication bias and selective reporting cannot be excluded. CONCLUSION Both commercially and locally developed CDSSs are effective at improving health care process measures across diverse settings, but evidence for clinical, economic, workload, and efficiency outcomes remains sparse. This review expands knowledge in the field by demonstrating the benefits of CDSSs outside of experienced academic centers. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Benefits and Harms of Breast Cancer Screening A Systematic Review

IMPORTANCE Patients need to consider both benefits and harms of breast cancer screening. OBJECTIVE To systematically synthesize available evidence on the association of mammographic screening and clinical breast examination (CBE) at different ages and intervals with breast cancer mortality, overdiagnosis, false-positive biopsy findings, life expectancy, and quality-adjusted life expectancy. EVIDENCE REVIEW We searched PubMed (to March 6, 2014), CINAHL (to September 10, 2013), and PsycINFO (to September 10, 2013) for systematic reviews, randomized clinical trials (RCTs) (with no limit to publication date), and observational and modeling studies published after January 1, 2000, as well as systematic reviews of all study designs. Included studies (7 reviews, 10 RCTs, 72 observational, 1 modeling) provided evidence on the association between screening with mammography, CBE, or both and prespecified critical outcomes among women at average risk of breast cancer (no known genetic susceptibility, family history, previous breast neoplasia, or chest irradiation). We used summary estimates from existing reviews, supplemented by qualitative synthesis of studies not included in those reviews. FINDINGS Across all ages of women at average risk, pooled estimates of association between mammography screening and mortality reduction after 13 years of follow-up were similar for 3 meta-analyses of clinical trials (UK Independent Panel: relative risk [RR], 0.80 [95% CI, 0.73-0.89]; Canadian Task Force: RR, 0.82 [95% CI, 0.74-0.94]; Cochrane: RR, 0.81 [95% CI, 0.74-0.87]); were greater in a meta-analysis of cohort studies (RR, 0.75 [95% CI, 0.69 to 0.81]); and were comparable in a modeling study (CISNET; median RR equivalent among 7 models, 0.85 [range, 0.77-0.93]). Uncertainty remains about the magnitude of associated mortality reduction in the entire US population, among women 40 to 49 years, and with annual screening compared with biennial screening. There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis. For women with a first mammography screening at age 40 years, estimated 10-year cumulative risk of a false-positive biopsy result was higher (7.0% [95% CI, 6.1%-7.8%]) for annual compared with biennial (4.8% [95% CI, 4.4%-5.2%]) screening. Although 10-year probabilities of false-positive biopsy results were similar for women beginning screening at age 50 years, indirect estimates of lifetime probability of false-positive results were lower. Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancy was low in quality. There was no direct evidence for any additional mortality benefit associated with the addition of CBE to mammography, but observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of CBE. CONCLUSIONS AND RELEVANCE For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.

Transitional Care After Hospitalization for Acute Stroke or Myocardial Infarction: A Systematic Review

BACKGROUND Transitional care is a time-limited service to prevent discontinuous care and adverse outcomes, including rehospitalization. PURPOSE To describe transitional care interventions and evidence of benefit or harm in patients hospitalized for acute stroke or myocardial infarction (MI). DATA SOURCES Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Cochrane Database of Systematic Reviews, and EMBASE, supplemented with manual searches of reference lists of relevant studies and review articles (January 2000 to March 2012). STUDY SELECTION 6 reviewers screened 5857 citations to identify English-language reports of trials or observational studies that compared transitional care with usual care among adults hospitalized for stroke or MI and that reported patient, caregiver, process, or systems outcomes within 1 year of hospital discharge. DATA EXTRACTION Data on study design, quality, population, intervention characteristics, and patient- and system-level outcomes were extracted by 3 reviewers and confirmed by 1 additional reviewer. DATA SYNTHESIS 62 articles representing 44 studies of transitional care for either acute stroke (27 studies) or MI (17 studies). Four intervention types were studied: hospital-initiated support (n = 14), patient and family education (n = 7), community-based support (n = 20), and chronic disease management (n = 3). Most studies (68%) were of fair quality. Overall, moderate-strength evidence showed that hospital-initiated support reduced length of stay for patients who had a stroke, and low-strength evidence showed that it reduced mortality for patients who had an MI. Evidence about benefits of other interventions and harms from transitional care services was insufficient. LIMITATIONS Few studies had high-quality research designs. The usual care comparator was often poorly defined. Applicability to U.S. clinical practice was limited; only 6 studies were conducted in the United States. CONCLUSION Available evidence shows that hospital-initiated transitional care can improve some outcomes in adults hospitalized for stroke or MI. Finding additional transitional care interventions that improve functional outcomes and prevent rehospitalizations and adverse events is a high priority for the growing population of patients who have an MI or a stroke. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Prioritization of patient-centered comparative effectiveness research for osteoarthritis.

Osteoarthritis (OA) is a leading form of disability in the United States and can affect weight-bearing and nonweight-bearing joints (1, 2). It can manifest as a generalized condition affecting multiple joint groups or a localized condition affecting only 1 joint. In OA, structural and then symptomatic failure of 1 or more synovial joints occurs with loss and erosion of articular cartilage, subchondral bone alterations, meniscal degeneration, limited synovial inflammatory response, and bone and cartilage overgrowth (3). Physical and psychological factors influence the symptoms of pain and stiffness in the joints affected by OA (4). Diagnosing OA can be complex, usually requiring a complete clinical history, physical examination, laboratory testing, and radiographic studies to help confirm the suspected diagnosis. Approximately 27 million adults in the United States are living with OA of 1 or more joints (5), and this number is projected to increase steadily over the coming decades because of an aging population and an increasing prevalence of obesity (6). In the Framingham Heart Study cohort, the prevalence of symptomatic knee OA has increased by 4.1% among women and 6.0% among men over 20 years (7). Osteoarthritis exacts a tremendous toll on patients and society; it ranks third (behind depression and alcohol misuse) in years lost to disability in the United States (8). Health care costs of OA are highand are increasing. Between 1997 and 2009, the number of hospitalizations with a primary diagnosis of OA more than doubled to an estimated 921000 (5). Moreover, the health care costs of inpatient, outpatient, and pharmaceutical treatment have been estimated to be 50% greater than those for persons without the condition (9). Nonsurgical management options for OA include analgesics and anti-inflammatory drugs, weight management, exercise, and physical therapy or a combination of these strategies (such as medication plus exercise). When medication and exercise or physical therapy are not enough to decrease pain and improve quality of life, joint surgery is another option. Each management strategy has tradeoffs. For example, persons with OA are twice as likely as those without to develop peptic ulcers (relative risk, 2.49 [95% CI, 1.37 to 4.51]) and renal disease (relative risk, 2.10 [CI, 1.10 to 4.01]), which are probably associated with high use of anti-inflammatory medications (10). However, evidence is limited on the relative benefits and harms of therapies within each category (medication, physical therapy and exercise, weight loss, or surgery) and there are few direct comparisons of effectiveness, in terms of patient-centered outcomes, among categories or combinations of categories. Given the high prevalence of OA and the effect on functional status, productivity, and quality of life, optimizing treatments to stabilize symptoms, reduce pain, and maintain functional status should be a high priority. The aim of this project was to develop, in collaboration with diverse stakeholders, a prioritized research agenda about OA management that would reduce uncertainty about nonsurgical management options and optimize patient-centered outcomes. Methods The Appendix Figure shows our methods, which were previously detailed (11). We identified and appraised recently published systematic reviews; clinical practice guidelines; and documents on future research needs, including an Agency for Healthcare Research and Quality report identifying future research needs for physical therapy for knee OA (12). On the basis of recommended areas for future research from these sources, we developed a draft list of 31 possible evidence gaps. Appendix Figure. Overview of prioritization process. Adapted from reference 19. ESG = Evidence Synthesis Group; PCORI = Patient-Centered Outcomes Research Institute. We then engaged a group of 13 stakeholders that included clinical experts and researchers in OA treatment strategies; representatives from federal and nongovernmental funding agencies, relevant professional societies, and related consumer and patient advocacy groups; and health care decision makers and policymakers. The stakeholders provided input on the draft list of evidence gaps. We modified certain gaps and added others on the basis of their feedback and then constructed a relevant analytic framework (Figure). Using a forced-ranking prioritization method (13), stakeholders prioritized the list of possible evidence gaps via Web-based surveys. Figure. Analytic framework. Italicized text indicates top-tier gaps. ADLs = activities of daily living; FRN = future research need; OA = osteoarthritis. We then performed 2 database searches to identify recently published and ongoing studies relevant to the future research questions that stakeholders ranked in the top tier. Database queries included a search of PubMed between 16 December 2008 and 16 December 2013 and ClinicalTrials.gov on 16 December 2013. We categorized topic areas and key characteristics of the identified studies. Finally, senior Evidence Synthesis Group investigators proposed appropriate study designs to address the stakeholders highest-ranked priority research areas. (Tables 1 and 2 of the Supplement] show the stakeholder panel and search strategies.) Supplement. Supplementary Data for Prioritization of Research Addressing Osteoarthritis Role of the Funding Source The Patient-Centered Outcomes Research Institute (PCORI) provided funding for this work. The funding source stipulated the topic for prioritization but did not participate in the literature search, determination of study eligibility criteria, data analysis or interpretation, or preparation or approval of the manuscript for publication. Staff from PCORI did review a draft version of the manuscript and provided suggestions to clarify language describing the process in selecting this topic for prioritization. Results Expansion of Evidence Gaps Through Stakeholder Engagement The stakeholder panel expanded the initial list of 31 evidence gaps to 48. The final list illustrated several common themes: Stakeholders stressed that future research should focus on engaging patients early in the disease process, helping patients navigate treatment options that optimize patient-centered outcomes (for example, negative affect, sleep, pain, and employment), and developing strategies that promote successful long-term engagement in nonsurgical treatment options. New questions suggested by the stakeholders addressed a wide range of evidence gaps related to the unique needs of subpopulations and the comparative effectiveness of diverse interventions. Stakeholders acknowledged that several patient groups received less attention than others and that it would be important to assess the comparative effectiveness of nonsurgical management strategies by sex, socioeconomic status, and prevalence and severity of comorbid conditions among adults and patients who had previously had surgical treatment of OA. Stakeholders stressed the progressive and chronic nature of OA and the importance of early detection and patient engagement. They also emphasized the importance of setting up patients for successthat is, that treatments should be tailored to patients abilities, insurance coverage, culture, and preferences. Stakeholders acknowledged that many current and ongoing studies focus on short-term outcomes and do not necessarily provide the needed information about long-term outcomes reflecting the chronic nature of the disease. They highlighted the importance of shared decision-making tools for not only exploring nonsurgical options but also discussing the optimal timing for transition to surgical interventions. They also stressed the incorporation of patient preferences for specific outcomes and their personal characteristics (and the effect of those characteristics on potential efficacy of treatment options) in such shared decision-making tools. Stakeholder Ranking of Future Research Needs The Appendix Table shows the 48 final potential research topics, the number of points each received, and the number of stakeholders who allotted points to each topic. The final ranking divides the possible evidence gaps into a top, middle, and lower tier on the basis of overall score. The top 12 future research needs (Table) prioritized by stakeholders were related to identifying key patient-centered outcomes; determining optimal duration, intensity, and frequency of interventions; examining the effect of socioeconomic differences on management strategies; determining the need for transition from nonsurgical to surgical interventions; promoting long-term behavior change; standardizing screening tools; evaluating biomechanical strategies; developing strategies to help patients engage in key self-management behaviors; promoting coordinated care in todays new health care delivery system; comparing methods for identifying and engaging patients early in the disease process; comparing safety and effectiveness of usual-care nonsurgical therapies; and identifying ways for setting patients up to succeed with nonsurgical management. Appendix Table. Final Ranking of Future Research Needs for Alternative Strategies for OA* Table. Top-Ranked Research Priorities and Recommended Study Designs or Suggested Analyses to Address Them Although the stakeholder group expanded the initial list to 48 potential future research needs, 18 of the final questions received no votes (5 questions) or 1 to 2 votes by at most 2 stakeholders (13 questions). Of the 12 questions ranked as highest priority, 2 were new questions that stakeholders suggested (questions focusing on the transition from nonsurgical to surgical interventions and on methods for setting patients up to succeed with nonsurgical management). The other 10 high-priority ranked questions were part of the original list of suggested future research needs. Of the 18 questions ranked low priority, 9 were from our original list and 9 were

Future Research Prioritization: Implantable Cardioverter-Defibrillator Therapy in Older Patients

ABSTRACTBackgroundAlthough the implantable cardioverter-defibrillator (ICD) is highly effective therapy for preventing sudden cardiac death, there is considerable uncertainty about its benefits and harms in older patients, especially in the presence of factors, other than old age, that increase the risk of death.ObjectiveTo develop a prioritized research agenda for the Patient-Centered Outcomes Research Institute as informed by a diverse group of stakeholders on the use and outcomes of the ICD in older patients.DesignThe existing literature was reviewed to identify evidence gaps, which were then refined by engaged stakeholders. Using a forced-ranking prioritization method, the stakeholders ranked evidence gaps by importance. For the highest-ranked evidence gaps, relevant recent studies were identified using PubMed, and relevant ongoing trials were identified using ClinicalTrials.gov.ParticipantsEighteen stakeholders, including clinical experts and researchers in the prevention of sudden cardiac death and ICD therapy, representatives from federal and non-governmental funding agencies, representatives from relevant professional societies, health care decision-makers and policymakers, and representatives from related consumer and patient advocacy groupsKey ResultsThe top 12 evidence gaps prioritized by stakeholders were related to the safety and effectiveness of ICDs in older patient subgroups not well represented in clinical trials, predictors of SCD, the impact of the ICD on quality of life, the use of shared decision-making, disparities in ICD use, risk stratification strategies, patient preferences, and distribution of modes of death in older patients.ConclusionsIn this paper, we identify evidence gaps of high priority for current and future investigations of ICD therapy. Addressing these gaps will likely resolve many of the uncertainties surrounding the use and outcomes of the ICD in older patients seen in clinical practice.

An overview and discussion of the Patient-Centered Outcomes Research Institute's decision aid portfolio

Decision aids (DAs) help patients make informed healthcare decisions in a manner consistent with their values and preferences. Despite their promise, DAs developed with public research dollars are not being implemented and adopted in real-world patient care settings at a rate consistent with which they are being developed. To appraise the sum of the parts of the portfolio and create a strategic imperative surrounding future funding, the Patient-Centered Outcomes Research Institute (PCORI) tasked the Duke Evidence Synthesis Group with evaluating its DA portfolio. This paper describes PCORIs portfolio of DAs according to the Duke Evidence Synthesis Groups analysis in the context of PCORIs mission and the field of decision science. The results revealed a diversity within PCORIs portfolio of funded DA projects. Findings support the movement toward more rigorous DA development, assessment and maintenance. PCORIs funding priorities related to DAs are clarified and comparative questions of interest are posed.

Prioritization of Research Addressing Antipsychotics for Adolescents and Young Adults With Bipolar Disorder

Bipolar disorder is characterized by episodes of mania (mood elevation, delusions, and extreme behaviors) alternating with severe depressive symptoms. It may develop during childhood or adolescence, and symptoms seem to be more severe when onset occurs at a young age (1, 2). Adolescents and young adults (aged <25 years) with bipolar disorder have high rates of substance abuse, hospitalization, legal issues, academic and psychosocial functional impairment, and suicide. These outcomes may occur more frequently when bipolar disorder coexists with other psychiatric disorders, low socioeconomic status, or abuse. The disorder also affects relationships and the financial security of the families. Up to 2.7% of persons aged 12 to 21 years have bipolar disorder, although rates may approach 5% when those with subsyndromal manic symptoms, who are also at elevated risk for morbidity, are included in estimates (3). Diagnosing the disorder in adolescents and young adults is complex and requires longitudinal assessment. Bipolar disorder may be difficult to distinguish from other disorders affecting adolescents and young adults, such as attention-deficit hyperactivity disorder and behavioral disorders, and diagnosis is further complicated by the fact that bipolar disorder may coexist with these other disorders. Psychiatric interviews and rating scales can be used for screening by trained clinicians, and parent-report instruments have also been used (46). Recovery is achievable in most adolescents and young adults with bipolar disorder (710), but almost 80% of the affected population relapse within 2 to 5 years (9). Options for treating the disorder include medications (for example, antipsychotic drugs, lithium, and certain antiepileptic drugs), behavioral therapy interventions, and peer support. A lack of high-quality longitudinal studies comparing the effectiveness of different therapeutic options in adolescents and young adults complicates treatment of this population. The use of antipsychotic agents to treat bipolar disorder in adolescents and young adults has increased significantly during the past 20 years (11). Several factors have contributed to this occurrence. First, high-quality randomized, placebo-controlled trials have shown that second-generation antipsychotics are effective antimanic agents (12). On the basis of these data, aripiprazole, olanzapine, risperidone, and quetiapine have received regulatory approval for pediatric bipolar mania. Second, head-to-head trials have shown second-generation antipsychotics to be superior to valproic acid and lithium for treating mania in children and adolescents (1315). Finally, recent promotion by the pharmaceutical industry spurred by new indications for pediatric bipolar disorder has increased use of second-generation antipsychotics. However, use of antipsychotics in adolescents and young adults remains controversial because of the paucity of population-specific data on which to base practice recommendations (16) and existing concern that bipolar disorder diagnosis may be applied too broadly, including for patients with chronic mood dysregulation (17). The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, includes a new diagnosisdisruptive mood dysregulation disorderto reduce premature bipolar disorder assignment, but concerns about the validity of this new diagnosis have been raised (18, 19). Antipsychotic medications may also produce significant adverse effects (16, 20). First-generation antipsychotics can cause extrapyramidal symptoms, dry mouth, sedation, and the neuroleptic malignant syndrome, whereas second-generation antipsychotics can cause weight gain, diabetes, dyslipidemia, and hyperprolactinemia. Because antipsychotic use among adolescents and young adults with bipolar disorder is increasing despite significant clinical uncertainty, further research exploring the comparative effectiveness of antipsychotics on patient-centered outcomes in these populations is needed. Using a process described on the Patient-Centered Outcomes Research Institute (PCORI) Web site and in our companion paper (21), a PCORI advisory panel has identified this topic as being of high interest for potential targeted funding. Accordingly, PCORI tasked the Duke Evidence Synthesis Group with creating a prioritized agenda for research in this area that would incorporate the perspectives of relevant stakeholders. Methods The Appendix Figure and the companion paper (21) detail the methods used to prioritize future research and develop recommendations. We surveyed existing literature with a focus on systematic reviews (2008 to 2013), particularly an Agency for Healthcare Research and Quality report identifying future research needs for antipsychotic use in children and young adults with various psychiatric conditions (22, 23). On the basis of recommended areas for future research from these sources, we developed a draft list of 21 possible evidence gaps (Table 1 of the Supplement). Appendix Figure. Overview of prioritization process. Adapted from reference 27 ESG = Evidence Synthesis Group; PCORI = Patient-Centered Outcomes Research Institute. Supplement. Supplementary Data for Prioritization of Research Addressing Antipsychotics for Adolescents and Young Adults With Bipolar Disorder We then engaged a group of 9 stakeholders, which included clinical experts and researchers in bipolar disorder, representatives from federal and nongovernmental funding agencies, representatives from relevant professional societies, health care decision makers and policymakers, and representatives from related consumer and patient advocacy groups (Table 2 of the Supplement). In each of these categories, we identified a person with clinical or methodological expertise. We received feedback on potential stakeholders from the Research Triangle Institute-University of North Carolina Evidence-based Practice Center, which wrote the aforementioned future research needs report on antipsychotic use in children and young adults (23), and from PCORIs patient engagement group. Potential stakeholders completed a statement of disclosure and were screened for conflicts of interest. We sought input from these stakeholders on our draft list of possible evidence gaps, and we modified certain gaps and added others on the basis of their feedback, which led to a finalized list. From this list, we constructed an analytic framework (Figure) by adapting a previously used framework and incorporating the stakeholder-refined list of possible evidence gaps (23). By using a forced-ranking prioritization method (24), stakeholders then prioritized the list of possible evidence gaps through Web-based surveys. We used this input to rank the finalized list of possible evidence gaps into 3 tiers of priority. Figure. Analytic framework. For topics related to the 10 highest-priority (top-tier) evidence gaps, we did a horizon scan for recent and ongoing studies by searching PubMed and ClinicalTrials.gov (2008 to 2013) for projects that presented original data or secondary analysis of data from a randomized, controlled trial (RCT), prospective or retrospective observational study, or registry; included data on first- and second-generation antipsychotic medications; included adolescents or young adults with bipolar disorder; and included outcomes that could be categorized according to the identified list of research priorities. Our search strategy is presented in Table 3 of the Supplement. We then determined the most appropriate study designs for the 10 stakeholder-ranked research areas of highest priority. Role of the Funding Source Funding for this work was provided by PCORI. The funding source stipulated the topic for prioritization but did not participate in the literature search, determination of study eligibility criteria, data analysis or interpretation, or preparation and approval of the manuscript for publication. The funding source did review a draft version of the manuscript and provided suggestions to clarify language describing the process in selecting this topic for prioritization. Results Expansion of Evidence Gaps Through Stakeholder Engagement All 9 invited stakeholders participated in teleconferences to refine and expand the initial list of 21 evidence gaps (Table 1 of the Supplement). Three themes emerged during these discussions, which informed our expansion of the list. First, stakeholders highlighted how uncertainty in distinguishing bipolar disorder from attention-deficit hyperactivity disorder and other behavioral disorders can complicate diagnosis and interpretation of existing research in younger patients. This uncertainty often necessitates treatment in the absence of a firm diagnosis, which may confound outcome ascertainment. In addition to diagnostic uncertainty, stakeholders pointed to uncertainty in how phase and severity of illness are best measured and how these factors affect treatment choices. Second, our stakeholders discussed how our focus on adolescents and young adults requires consideration of a broad set of patient-centered outcomes in potential studies. These include outcomes measured over long periods; developmental outcomes; functional status outcomes; outcomes relating to parents, caregivers, or family members, including economic outcomes; and outcomes related to offspring in women of childbearing age (such as pregnancy, neonatal, and childhood outcomes). Finally, although the specific clinical domain addressed by this project focused on antipsychotic drug therapy, our stakeholders emphasized that the efficacy of such therapy for bipolar disorder in adolescents and young adults compared with alternative drug classes remains uncertain for many subgroups of patients. As such, stakeholders believed that attention needed to be given to research comparing antipsychotics with alternative treatment strategies, including lithium, antiepileptic drugs, and adjunctive nonpharmacologic treatments (such