Movement Disorders Vol. 17, Suppl. 4, 2002, p. i 2002 Movement Disorder Society Published by Wiley-Liss, Inc. DOI 10.1002/mds.5554 Editorial Management of Parkinson’s Disease: An Evidence-Based Review* Although Parkinson’s disease is still incurable, a large number tomatic control of Parkinson’s disease; prevention of motor com- of different treatments have become available to improve quality plications; control of motor complications; and control of non- of life and physical and psychological morbidity. Numerous jour- motor features. Based on a systematic review of the data, efficacy nal supplements have appeared in recent years highlighting one conclusions are provided. On the basis of a narrative non-system- or more of these and disparate treatment algorithms have prolifer- atic approach, statements on safety of the interventions are given ated. Although these are often quite useful, this “mentor analy- and finally, a qualitative approach is used to summarize the impli- sis” approach lacks the scientific rigor required by modern evi- cations for clinical practice and future research. dence-based medicine standards. The Movement Disorder Soci- This mammoth task has taken two years to complete and the ety, with generous but unrestricted support from representatives task force members, principal authors and contributors are to be of industry, have, therefore, commissioned a systematic review congratulated for their outstanding work. Physicians, the of the literature dealing with the efficacy and safety of available Parkinson’s disease research community and most of all patients treatments. The accompanying treatise is the result of a scrupu- themselves should welcome and embrace the salient findings of lous evaluation of the literature aimed at identifying those treat- this report as an effort to improve clinical practice. It is hoped that ments for which there is sound scientific support to justify their this supplement will serve as a landmark in the treatment of application (or avoidance) and to highlight where a lack of evi- Parkinson’s disease, not only encouraging ongoing excellence in dence points to the need for future clinical trials. The introductory patient care but also providing guidance in the development of chapter reviews the study methodology while subsequent chap- future research studies designed to fill the identified gaps in our ters deal with specific interventions subdividing the evidence un- current knowledge base. der the categories of: prevention of disease progression; symp- Anthony E. Lang, MD, FRCPC Andrew Lees, MD, FRCP Co-Editors-in-Chief *Produced by a task force commissioned by The Movement Disorder Society Movement Disorders Vol. 17, Suppl. 4, 2002, p. S1-S6 2002 Movement Disorder Society Published by Wiley-Liss, Inc. DOI 10.1002/mds.5555 Introduction Many therapeutic interventions are available for the manage- clearly formulated and focused question. A systematic review is ment of Parkinson’s disease including drugs, surgical interven- also characterized by the use of systematic and explicit methods tions and physical treatments. They are not equally accessible and to identify, select, and critically analyze the relevant studies. Fur- their real clinical value, as measured by their impact on clinically thermore, the systematic review analyzes and summarizes the data relevant outcomes, has not always been established through high presented in the studies included in the review.4 quality, randomized, controlled clinical trials. In contrast, some Sometimes systematic reviews use meta-analyses to provide a therapeutic interventions have been well studied in controlled clini- summarized statistical analysis of the data available. However, cal studies and appear to be underused (as evidenced in other meta-analyses are not a required component for a review to be medical fields1). This underuse may actually be due to the lack of systematic. The use of meta-analysis is considered optional and awareness of the supporting clinical evidence that is documented should be viewed as an available tool. in the medical literature. Furthermore the research programs on In this project, each chapter aims to be a systematic review of specific therapeutic interventions or procedures are frequently es- the efficacy of each of the therapeutic interventions identified. The tablished by industry as part of the drug development process and safety discussion within these chapters uses a narrative, unsys- not necessarily to fill gaps in the available clinical evidence. tematic approach due to the complexity of the literature published To identify areas that are understudied and/or where evidence to date on safety of the different therapeutic interventions. This is is lacking, a clear understanding of what has been established an obvious limitation of the work. through clinical research is required. The tools used in evidence- The most relevant clinical questions addressed during a sys- based medicine are useful in this context. tematic review are questions centered around specific medical Evidence-based medicine2 is a neologism. As such, many dif- problems, symptoms or processes, and not necessarily on the effi- ferent meanings for the same concept may be intertwined in the cacy of therapeutic interventions outside a specific context. How- reader’s mind. To clarify this, we accept in this review the original ever, there are some advantages in using therapeutic interventions definition proposed by Sackett and colleagues3: as the organizational center of the review instead of the clinical “Evidence-based medicine (EBM) is the integration of best re- problem. This approach reduces the complexity of the review al- search evidence with clinical expertise and patients values; by best lowing each chapter to focus on a simple topic, while meeting the research evidence it is meant clinically-relevant research, often generic aims of this project. Thus, single treatments are reviewed from the basic sciences of medicine, but especially from patient independently instead of management strategies that may involve centered clinical research into the accuracy and precision of diag- a multitude of treatment options at the same time or in sequence. nostic tests (including the clinical examination), the power of prog- Practices and treatments for management of Parkinson’s dis- nostic markers, and the efficacy and safety of therapeutic, reha- ease vary worldwide, and are limited by individual treatment set- bilitative and preventive regiments.” tings and resources. Therefore, this document does not provide The Movement Disorder Society (MDS) in order to contribute practice guidelines because such guidelines are much more ap- to the practice of EBM has commissioned an evidenced-based re- propriately developed by local or regional institutions.5 view of current pharmacological and selected non-pharmacologi- This evidence-based review does not include quantitative sum- cal practices commonly used to manage patients with PD. To this maries (no meta-analyses were conducted) of the different data end, a task force of clinical movement disorder experts and clini- sets. The main reason to avoid quantitative summaries was the cal pharmacologists was established. Members of this task force overwhelming workload of such a task. The qualitative approach, were the principal authors and co-authors of this document. The such as the one undertaken here, is anyhow an important contri- challenge lay in the fact that for many treatments currently avail- bution to highlight the evidence available and it facilitates the in- able, effect sizes or risk-benefit relationships have not been sys- clusion of some subjectivity and expert opinion. This is explicitly tematically studied in well-designed controlled trials. A coordi- limited to the two sections within each chapter entitled: (1) Impli- nated effort was undertaken to review the published information cations for Clinical Practice, and (2) Implications for Future Re- available to date, and determine the benefits and limitations of dif- search. ferent pharmacotherapies and treatment strategies for managing It is worth noting that in some instances the conclusions herein patients with PD. To achieve this goal, a couple of strategic op- may differ from the available Cochrane reviews6 on the same topic. tions were considered in order to limit the task to a realistic amount When these conclusions differ, this review may be considered less of work. In this chapter those strategic options and the methodol- conservative than The Cochrane Reviews. This reflects the differ- ogy followed are described. ences in the methodology used. Cochrane reviews (1) are more comprehensive as based on a broader sources of data retrieved STRATEGIC OPTIONS (with less publication and language selection bias; further described A systematic review is a research program organized around a below), (2) use meta-analysis when possible, and (3) limit conclu- S1 S2 Introduction sions to the boundaries of evidence reviewed, thereby avoiding Table 1 Specific Treatments Reviewed subjectivity.7 The merit of both approaches is the transparency – defined as including full description of the methods, disclosure of the criteria Indication for evidence retrieval, and a clear understanding on how conclu- • Prevention of disease progression sions are reached. This transparency makes it easier for the read- • Symptomatic control of parkinsonism ers to spot differences between two approaches and allows their • Prevention of motor complications own interpretation