Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources – especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development – the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF).A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline.Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations  – the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer.The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines. Evidence-based clinical practice guidelines have considerable potential to improve health care, and their international production has increased substantially over the past two decades -3. HowevA number of projects have sought to adapt or adopt existing guidelines -14, on tAdditionally, implicit normativity has been shown to be inherent in guidelines – from the search for and critical appraisal of evidence, to its presentation, and the formulation of recommendations . ContextAll of these issues give rise to methodological challenges for adaptation processes. In recognition of this, the ADAPTE group  has propThe SGR was conducted as the first step in the development of a new guideline on chronic heart failure for use by family physicians in Germany. After having carried out the SGR, the resulting draft guideline underwent further development in accordance with institutional standards , which aTo develop an evidence-based guideline on chronic heart failure (CHF) for use in German primary care we defined, a priori, the key premises of the target guideline: the definition of the target condition, its epidemiology, the target setting, the need for change in healthcare, and the outcome parameters of interest.We designed the SGR method comprising the nine steps grey tagged in FIGURE In March 2004 one of us (CM) performed a systematic literature search for existing guidelines in MEDLINE, The Cochrane Library, DARE, and HSTAT; combining controlled terms and free text, complemented by a comprehensive hand search of web-based resources  independently appraised the retrieved guideline-documents for eligibility (yes or no). Discrepancies were resolved by consensus, and kappa-statistics were calculated for observer variability according to Cohen . To be iA guideline was excluded, if it referred exclusively to pediatric patients, isolated right heart failure, special or inpatient care, or no information on development methods was given . Guidelines with a focus only on particular aspects of heart failure management (e.g. guidelines on echocardiography) were excluded from the SGR.The quality of the guideline was assessed using the standardized Appraisal of Guidelines Research and Evaluation (AGREE) instrument ,40. AGREAGREE is suggested for multiple raters. The appraisal is based on the consideration of the whole guideline and is therefore of wider scope than the evidence review and synthesis reported here. Nevertheless, it does include any recommendations on diagnosis, monitoring, or prevention and the proposed multiple rater scheme is thus rather time-consuming. Because we had only limited resources available to us, we performed a single rating (CM) for this step of the guideline development process.To build a framework of relevant issues, clinical questions from the included guidelines were derived by one reviewer (CM), appraised for their relevance and prioritized in terms of the target context by three others . For each clinical question the data were extractedinto evidence tables of a standardized format which included recommendation(s), evidence level(s), grading, critical appraisal of evidence, and cited sources.One reviewer (CM) systematically compared guideline recommendations for every clinical question for their external consistency (e.g. between guidelines), and their reported evidence. We categorized our findings into six types Table : four tyFor a critical re-appraisal of whether recommendations were supported by valid study results, the most relevant evidence cited in the included guidelines was selected by applying the highest levels of evidence from the Oxford Centre for Evidence-Based Medicine . PredomiFinally, the evidence and recommendations were synthesized in a draft of the target guideline, and the results and possible methodological flaws of the included source-guidelines, and the re-assessed studies, were discussed. For specified clinical questions without identified high-quality evidence and for the necessary update-searches to ensure the actuality of the guideline, a structured list was formed to define the need for further research.Our literature search resulted in 699 citations, of which 52 were potentially relevant. A total of 16 evidence-based guidelines met our inclusion criteria . To extract the data we entered all relevant information into evidence tables in the above mentioned format.Within the framework we identified 35 recommendations. Of these, 25 recommendations were consistent, nine were inconsistent, and one was not rateable (derived from a single guideline). Of 25 consistencies, seven were based on strong evidence (types 1 and 2), 14/25 on weak evidence or expert consensus (type 3), and 4/25 were consistent in content, but had different evidence levels (type 4). Only one inconsistent recommendation  was based on expert consensus, the remaining inconsistencies differed in their evaluation of the empirical findings (types A and B).While we found type 1-, 2-, and 4-consistencies mainly in recommendations on pharmacotherapy (Table Among nine inconsistencies we classified three as major inconsistencies (type A): (1) The use of brain natriuretic peptide testing in patients when CHF is suspected Table ; 2) Ang Ang2) AnSeventeen partly complex recommendations were categorized as consistency types 1, 2, 4 (n = 11), and inconsistency type B (n = 6)  with or without meta-analyses, six RCTs and one post-hoc subgroup analysis of an RCT, since this study was linked to a warning sign in one guideline. The reasons for preclusion of the remaining studies are given below Table . The valAll included guidelines recommended the use of ACE inhibitors in all NYHA classes including asymptomatic patients. While 11 guidelines designed differentiated clinical outcomes as therapeutic goals in asymptomatic patients , three guidelines ranked evidence-level highest for a mortality reduction in this subpopulation, and two guidelines used ambiguous formulations. We found no evidence from the cited studies for a mortality reduction in asymptomatic patients, since this subpopulation was underrepresented in RCTs. Evidence was found only when we identified an health technology assessment report in further searches . Compara2-test detected no heterogeneity despite high clinical heterogeneity between the studies, no sensitivity analyses to test the robustness of the results). In conclusion, the evidence level remained unclear: formally, multiple RCTs have shown positive effects on (different) clinical outcomes of diuretics, but the methodological quality of the meta-analyses (and the RCTs themselves) give a high probability of biased results.Fourteen guidelines recommended the use of diuretics, reported evidence levels and graded their recommendations: in 2/14 diuretics were recommended to reduce mortality and morbidity in CHF. The supporting evidence was ranked highest and linked to a systematic review including meta-analysis (published in 2002) , which wThe evaluation of pharmacotherapy in the source guidelines often focused on treatment benefits and underestimated the risks, such as of adverse events, following the combination of ARBs and ACE inhibitors, or the risk of hyperkalemia following the use of aldosterone antagonists, as recently shown ,77.We summarized the SGR results in a draft guideline for the following steps in development and formed a list of specific clinical questions for further research comprising all type-3-consistencies, type-A-inconsistencies and incongruity from the validation process. To adjust the research needs to the given resources these research questions were formally prioritized for the search for new evidence by representatives from the targeted user groups after conducting the SGR (outside the scope of this paper).Our methodological concept of the systematic guideline review had to be planned with exceedingly limited resources for the whole project (the budget was € 75.000), but was successfully completed after 8.5 man-months. Starting in January 2004 with the development of the methods concept and systematic searches for guidelines, the first part of the SGR was finished by one researcher (part time: 75%) by the end of June 2004, accounting for 4.5 man-months. From July 2004 to February 2005 the validation procedure was conducted and the draft guideline was written by one researcher (50%), accounting for the remaining four man-months.Our study addressed the need for a high-quality evidence-based guideline to manage patients with CHF in the German primary care context. Internationally, several high-ranking guidelines were/are already in existence, but adaptation methods have not been established yet ,79. The CHF is a syndrome with a number of distinct clinical presentations . 'AskingWe carefully compared recommendations and the judgments of underlying evidence reported in the guidelines. Like Kulig et al., we found good overall  consistency . NeverthWe critically re-appraised the most important evidence sources cited in the guidelines to assess whether design, study-population and results were able to support the recommendations in our setting. Certainly, the vast majority of recommendations was justified by empirical findings, but some were not. Examples such as strong recommendations for drug therapy in asymptomatic patients, which were not sufficiently based on the highest level of evidence  shed a light on methodological shortcomings even in those guidelines that were of high quality according to the AGREE appraisal. Our reported findings fit in well with recently published studies: McAlister et al.  have shoSome of our judgments might seem overcritical to the reader. But the questions on how to compare and combine different sorts of evidence (e.g. benefits and risks) or conflicting study results reflect not only the under-use of current approaches to grade the evidence (e.g. the GRADE- or CHEP-system) ,90 but aIn comparison to adaptation procedures – e.g. the most ambitious approach by Fervers et al  – our SGFurthermore, our SGR method contributed to resource saving: The total costs for the guideline development (incl. the consensus process) were about € 75,000. Though the following examples do not allow a head-to-head comparison, they describe the context: for the 1997 Scottish guideline on 'The management of mild, non-proteinuric hypertension in pregnancy' the total costs were given as £ 66,809  ; the ave) to diminish the potential effects of an observer bias on the target guideline.Our study had some limitations such as the lack of a second review in data extraction and further steps of appraisal. Therefore, a certain observer bias cannot be ruled out. Our budget allowed only a single AGREE appraisal. Fortunately, we were able to compare our results with another working group of the German Agency for Quality in Medicine (AQuMed/ÄZQ) (two appraisers), which carried out a quality appraisal of the same guidelines subsequently and independently of us. Their results were quite similar with a slightly better rating than ours . However, this bias is less probable in our study, since we included guidelines from several countries, differing in funding and reimbursement ,98, avaiFurther, our findings on the resource saving effect of the SGR have to be interpreted within the context of this study: our paper reports on an uncontrolled N = 1 group study and the resource data were collected retrospectively.Nevertheless, our findings in the SGR were relevant to the recommendations in our guideline, assured their validity, contributed to its transparency, highlighted fields of implicit normativity to prepare an open discourse during the later stages of guideline development , and saved resources by avoiding unnecessary redundancies in the literature search and appraisal. Further studies should be carried out with the involvement of a second reviewer to avoid observer bias.The systematic guideline review method is a valid means of making use of existing guidelines, and allows a systematic approach to the development of a new guideline. A systematic guideline search aims at the inclusion of guidelines from different healthcare systems, and a systematic comparison of recommendations brings to light both mainstream recommendations and controversies, but also the grey zones of clinical practice. A careful re-evaluation of the most relevant evidence sources assures validity. In the trade-off between breadth and depth, the SGR allows reasonable and transparent prioritization in order to concentrate the development resources on the most important questions for further research. The SGR helps to highlight fields of implicit normativity in guidelines and prepares them for an open discourse within the target context. It abbreviates the initial full evidence review stages, and helps to avoid unnecessary repetition of high-quality research by other guideline authors. In our example it allowed the development of a guideline on the complex clinical issue of chronic heart failure with comparatively small resources. Further studies will have to confirm our results to develop a valid guideline by means of the SGR.The authors declare that they have no competing interests.CM had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. She designed the study, acquired, analyzed and interpreted the data and drafted the manuscript. JG, MB and FMG were involved in the study concept and design, supported data acquisition, analysis and interpretation and the critical revision of the manuscript for important intellectual content. AH substantially contributed to the data analysis and interpretation and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Supporting Web-based Material. The file contains the following tables, as mentioned in the text: – List of websites consulted in hand searches: International Organizations (Table W1). – List of websites consulted in hand searches: National Organizations (Table W2). – Checklist by the German Working Group on Health Technology Assessment: an example for systematic reviews with/without meta-analyses (Table W3). – List of excluded guidelines with the reason for preclusion (Table W4). – Results of Consistency Analyses: List of Type-3-Consistencies and Type-A-Inconsistencies (Table W5). – Comparison of different quality appraisals for the included guidelines (Table W6).Click here for file


In response to Banzi's et al review of online evidence-based practice point-of-care resources published in the Journal of Medical Internet Research, the publisher of DynaMed clarifies his evidence-based methodology. We congratulate Banzi and colleagues for publishing a review of online evidence-based practice point-of-care resources . It is iThe adherence to evidence-based methodology for development and maintenance of these products is important for maintaining trust and validity in the content used by practicing clinicians. Banzi et al evaluated evidence-based methodology for point-of-care resources based on published marketing materials and editorial policies as stated on the websites of the publishers.We were surprised to see a score for DynaMed  which was less than 100% for our “evidence-based methodology”. In fact, “evidence-based methodology” is the fundamental methodology for how our editors are trained and how we work on a daily basis. A 7-step evidence-based methodology is the core process for updating and maintaining DynaMed .The specific rating difference appears to be for the question “Are systematic reviews preferred over other types of publication?”. We should clarify that we absolutely prioritize systematic reviews (preferably Cochrane reviews) in our hierarchical approach to content consideration for inclusion, placement of content, and sources for deriving overall conclusions for evidence synthesis and overview statements. Individual study summaries are often deleted when included in a subsequent systematic review unless the individual studies offer additional information.However, our editorial policy page referred to the concept without explicitly describing the hierarchy used. We have now updated our editorial policy page to make this more explicit . This isThank you to Banzi et al for bringing this to our attention.


The present generation of clinicians is able to draw better conclusions on the past practices and use them to alleviate pain, suffering and prolong the life expectancy of human beings. The sound training of the future generation of health personnel and learning from the past experiences is most important for continued evolution of medical science and dissemination of the knowledge far and wide.The present issue of Indian Journal of Orthopedics has two writings on orthopedic education. The Orthopedic education is far more organized in United States and Europe and now some of the finer issues such as mentorship,We are in the era of information technology, where a plethora of information is available for use. Some times excessive information also creates confusion and doubts in the mind of the user. It is important to draw reliable conclusions for everyday clinical practice. The conclusions based on scientific analysis of the literature stand the test of time and predictably help to plan management. The present issue has review article by Handoll et al. on “The Cochrane Collaboration: a leading role in producing reliable evidence to inform healthcare decisions in musculoskeletal trauma and disorders” highlighting the methodology of the Cochrane collaboration in generating evidence for clinical practice. Systematic reviews of articles and Randomized controlled trails(RCTs) are important to develop evidence-based guidelines. The very bases of such reviews are defining clear research questions, analysis of eligible studies collected by an explicit, and predefined systematic search of the literature and analyzing scientifically to draw robust evidence.This implies that for systematic reviews, sufficient articles/RCTs for a specific research question are required. The publication of studies depends on the prevailing clinical problems in a geographical area, desire of clinicians to analyze the clinical data, infrastructure to conduct the studies and publication in retrievable (indexed) journals.The clinical problems of developing countries are diagonally different from those of developed nations.The surgeons in developing countries are burdened by a large number of patients, poor infrastructure to treat and conduct research, less incentives for research and lack of enthusiasm to publish. Most of the indexed journals are published from developed countries and are less inclined to accept articles on the problems of developing countries. With the present approach of the “Cochrane group” it looks an improbable task to generate the evidence when published data is not available from developing countries on their clinical problems.This can be done by creating a collaborative of orthopedic surgeons who are desirous to create evidence. The collaborative should include “subspecialties” of the musculoskeletal system. The list of research questions, the research strategies to find out available evidence needs to be drawn, failing which specific research is to be conducted to generate evidence for day-to-day clinical problems. This will help in formulating guidelines for the management of various musculoskeletal disorders in developing countries.The developing countries will have to work in multiple directions. At one end they have to work hard to generate evidence for improving patient care in their available infrastructure at other end they need to keep pace with west in upgrading orthopaedic education, so that the future surgeons are prepared to take the lead role in research, generating evidence to improve patient care at large.


To examine how journals and magazines disseminate research evidence and guidance on best practice to health professionals by aligning commentaries on measles, mumps, and rubella vaccine (MMR) evidence in journals with key events in the MMR controversy.Content analysis.Comment articles in six commonly read UK publications.Number of comment pieces by publication, year and article type; trends in the focus, tone and inclusion of recommendations on MMR.BMJ n = 104, Community Practitioner n = 45, Health Visitor n = 24, Practice Nurse n = 61, Nursing Standard n = 61 and Pulse n = 565). Of these 860 comment pieces, 264 made some reference to evidence endorsing the safety of MMR. Around one in 10 were rated as negative  or neutral  in relation to MMR safety, and nearly a quarter  were rated as mixed. Following the publication of Wakefield et al’s 1998 paper there was a period of neutrality. In 2000, despite growing public concerns and widespread media coverage, fewer than 20 comment pieces were published. Less than a quarter of comment pieces  included recommendations.860 articles met the inclusion criteria (While a period of neutrality may reflect a professional response to uncertainty by holding back until consensus emerges, it may also represent a missed opportunity to promote evidence-based practice. BMJ identifies “Helping doctors make better decisions” as one of its objectives, and the magazine Pulse brands itself as “Informing, supporting, championing” GPs, while Nursing Standard states that it brings its readers “exclusive, up-to-the-minute coverage on issues affecting nursing practice”.Clinical journals are an important vehicle for the dissemination of research findings to health professionals. However there is debate about how effective such outlets are in bridging the gap between evidence and practice,This study explores how these publications do this by examining the alignment between trends in their reporting of measles, mumps, and rubella vaccine (MMR) evidence, and important events in MMR vaccination “controversy” between 1988 and 2007 see . This co6BMJ  to all BMA members and other subscribers), Health Visitor, Community Practitioner , Pulse , Practice Nurse (published fortnightly) and Nursing Standard (published weekly). Each publication was reviewed to identify the sections that commented upon or distilled evidence. The journal sections identified for inclusion were editorials, commentaries, news, news analysis, reviews of clinical papers, education and debate articles, art and science articles and feature articles. Collectively we refer to these eligible articles as “comment pieces” We excluded letters, views, book reviews and primary research articles.The most commonly-read journals and magazines aimed at community practitioners were identified through telephone interviews with health visitors, practice nurses, general practitioners and medical librarians (n = 20) working in Scotland and England, and through a survey  conducted at the Community Practitioners’ and Health Visiting Association (CPHVA) 2007 annual conference. The six most commonly cited sources were: Initial searches showed that CINAHL and Embase offered the best coverage and indexing of these publications, so further searches in these databases were conducted from 1988 to 2007 to cover the whole period since the introduction of MMR into the childhood immunisation programme (CIP). (Full search strategy available from the authors.) Manual searches were also conducted. This process identified 936 potentially relevant commentaries.Each comment piece was assessed by two reviewers for eligibility (n = 860). A coding frame (available on request) was developed, based on a random selection of 24 comment pieces from each journal, and tested and refined on subsequent samples to achieve consistency.Pulse . The BMJ published 104 comment pieces (12.1%). Practice Nurse and Nursing Standard both published 61 pieces (7%), Community Practitioner published 45 (5.2%) and Health Visitor 24 (2.7) pieces. The most common article type was news articles  followed by feature , review  commentary  and editorial  pieces.The majority of comment pieces were published in et al’s paper.A time line detailing key events in relation to MMR is available from the authors. An initial peak in the number of commentaries in 1988 covering the introduction of MMR into the CIP was followed by an apparent reduction in interest until 1994, when the Department of Health introduced the school-based “MR catch-up”campaign, “Operation Safeguard”. In 1998Pulse. There were 75 comment pieces whose main focus was on endorsing MMR vaccination, while 50 (5.8%) primarily focused on potential adverse side effects.The most common focus of the 860 comment pieces was on the delivery of the CIP programme . Most  were published in Less than a quarter of comment pieces  offered advice or recommendations. In the two-year period following the publication of the Wakefield paper in 1998 there were very few comment pieces containing recommendations, perhaps reflecting general uncertainty about MMR evidence among the editorial teams of these journals and magazines. Recommendations appeared more commonly during 2001 and 2002, although they still featured in only a minority of comment pieces.et al’s 1998 paper there was a period to 2004 during which many articles adopted a mixed, negative or neutral tone  made some reference to evidence endorsing the safety of MMR. Just over half of these 264  were rated as having a positive tone. Around one in 10 were rated as negative  or neutral . Following the publication of Wakefield ral tone . After tOur analysis highlights how uncertainty about evidence is reflected in the tone of professional journals and magazines. This was particularly evident in the period from 2001 to 2003 when many of the publications conveyed ambiguous messages about MMR safety, though there was little scientific disagreement that MMR was safe and there was scientific consensus from early on that the Wakefield study was neither generalisable nor robust. For at least two years following the publication of the Wakefield paper, there was also an information gap, with relatively few articles published.Pulse was on potential adverse side effects of MMR, a focus more closely aligned with the popular media’s representation that there were two competing bodies of MMR evidence,There were surprisingly few journal editorials on MMR during this period, and only three appeared in nursing journals. This postponement of a robust defence of MMR may have contributed to undermining confidence among health professionals, particularly since health practitioners working at the “coal-face” needed immediate reassurances about MMR safety once the issue was raised in the popular press. While a period of neutrality may reflect a professional response to uncertainty by holding back until consensus emerges, it may also represent a missed opportunity to promote evidence-based practice. Indeed, over this period the main focus of articles in Health practitioners use the editorials and commentary sections of journals to help keep up to date with research developments and to inform their practice.These sources can play an important part in synthesising and disseminating guidance on current best practice to health practitioners, particularly when there is conflicting evidence, such as during a health controversy.During the MMR controversy the slow response of journals and lack of recommendations may have added to clinical uncertainty, and increased the gap between evidence and practice.When new research attracts media attention but contradicts the existing evidence base, journals and magazines need to take a more proactive stance in translating the evidence to provide practitioners with clear guidance.Pulse), the findings clearly highlight the tensions for journal editorial teams, and prompt reflection on how far journals need to go in leading opinion during public health controversies. The analysis also identifies clear missed opportunities to accurately inform practitioners about the evidence during this period, such as periods when some journals and magazines appeared to “stand back” and wait for consensus to develop. When controversy is at its height such uncertainty and neutrality may be perceived by public and practitioners as further evidence that a problem exists, and such voids may create new opportunities for alternative or speculative views to arise.Although the study is limited by the dominance in the data of one magazine (


Symposium: A Practical Approach to Evidence-Based OrthopaedicsThe process of scientific discovery is, in effect, a continual flight from wonder.Albert EinsteinJournal of Bone and Joint Surgery adopted EBM and levels of evidence grading for all clinical papers. Since then, all major North American orthopedic meetings and journals have adopted evidence-based orthopedic teachings in some format or another.Evidence-based medicine (EBM) was recently noted as one of the top 15 medical discoveries over the past 160 years. The term EBM has become so commonplace in the practice of medicine that it seems hard to believe that the term, itself, was only coined in 1990 at McMaster University (Canada). The popularity of EBM has only recently expanded to evidence-based orthopedics. In 2003, the Evidence-based orthopedics requires an understanding of a new language and principle in the evaluation of clinical research and its impact on patient decision-making. While the concepts may not be entirely intuitive, they are an absolute prerequisite to any surgeon who wishes to practice in the era of EBM. Educational efforts have largely focused on medicine with little focus on the unique educational needs of surgeons. The unique features of surgical research and the associated challenges have often been minimized by researchers and practitioners promoting double randomized controlled drug trials as the gold standard.The current symposium has been developed to cover practical concepts of evidence-based orthopedics including its history, definitions, quality of the literature, checklists for surgeons to evaluate orthopedic literature and communication with patients.The core articles were developed by researchers at McMaster University in collaboration with experts from Boston (Massachussetts), Toronto (Ontario), Greenville (South Carolina), Zurich (Switzerland), Kiel (Germany), New Delhi (India) and Pune (India).


To the Editor:against the use of intrauterine devices (IUDs), the evidence cited for this is thin. It is based solely upon two cases reported in a single article in 1981 . This letter is a call to the research community in the fields of organ transplantation and family planning to collaborate in an effort to investigate this important issue in more detail. Following this, appropriate, evidence-based recommendations could be made to aid clinicians and patients in selecting the best method of contraception. This will ensure that women with transplants remain healthy and are given the best opportunity to experience a healthy pregnancy.


The UK Cosmetic Surgery Interspecialty Committee has defined cosmetic surgery as an area of practice involving  person"."a subspeciality of medicine and surgery that uniquely restricts itself to the enhancement of appearance through surgical and medical techniques. It is specifically concerned with maintaining normal appearance, restoring it, or enhancing it beyond the average level toward some aesthetic ideal".The American Board of Cosmetic Surgery has defined cosmetic surgery as According to statistics from the American Society for Aesthetic Plastic Surgery (ASAPS) in 2005, there were nearly 11.5 million surgical and nonsurgical procedures performed in the United States.[The top five nonsurgical cosmetic procedures in 2005 were:Botox™ injections Laser hair removal Hyaluronic acids: Hylaform™, Restylane™ Microdermabrasion Chemical peels Women had nearly 10,500,000 cosmetic procedures performed in 2005, accounting for 91.4% of the total. Men had 985,000 procedures, approximately 9% of the total. People between the ages of 35 and 50 years accounted for the majority of procedures (accounting for 5.3 million (47%) procedures. Those between 51 and 64 years accounted for 24%, patients aged between 19 and 34 years accounted for 24%, those 65 years and older accounted for 5%, and those aged 18 years and under accounted for 1.5%.The most common procedures for those aged 18 years and under were laser hair removal, microdermabrasion, rhinoplasty (nose reshaping), otoplasty (cosmetic ear surgery), and chemical peel. The majority (48%) of the cosmetic procedures were performed in an office facility, 28% in a free-standing surgi-center, and 24% in a hospital.Americans spent approximately $12.4 billion on cosmetic procedures in 2008.[Due to the increasing demand for aesthetic procedures, it is not uncommon for patients to encounter a menu of aesthetic supplies and procedures. These range from skin care products, skin rejuvenation , anti-wrinkle treatment, acne scar treatment, pigment removal, stretch mark removal, neck lifting, hair restoration, hair removal, breast firming/enlargement, skin whitening, cellulite removal, lip enhancement, tattoo removal, broken capillary treatment, square jaw treatment, nonsurgical facelift, fat removal, anti-aging medicine, hormonal therapy to mesotherapy.e.g., the beauticians and spa operators, have jumped onto the bandwagon to provide such services.Numerous skin rejuvenation treatment programs , skin rejuvenation procedures  have been introduced by dermatologists and plastic surgeons and subsequently, by diverse medical specialities. Nonmedical practitioners, Many of these aesthetic treatments claim to rejuvenate the skin but are not supported by good scientific evidence. Services and procedures that are unproven in efficacy by medical practitioners are often provided at significant cost to patients, which is considered by many medical practitioners to be a deviation from the normal practice of modern medicine. Many medical practitioners have perceived such deviations to be a growing problem that needs to be addressed as it undermines the trust in and professionalism of the medical fraternity.Concerns have been raised regarding safety issues as well as the quality of such services by the medical profession and the public. Some patients even sustain injuries and complications from these procedures.Several factors can be attributed to the increasing demand for aesthetic dermatology procedures, namely, (1) the secular consumer culture among the population at large to prolong youthfulness and self-image, (2) economic abundance, in particular, among well paid executives during good economic climates and the large proportion of retiring baby boomers who have accumulated sufficient savings as they reach their retirement age, (3) technological and medical advances whereby new cosmeceutics and devices have been invented to treat cosmetic disorders with minimal downtime and complications, (4) media-driven demand and hype promoted by some beauticians, medical practitioners, and the cosmeceutical and medical devices industries, (5) high-pressure advertising by various media, (6), a breakdown of institutions and cultural constraints, philosophy, policies etc and, (7) a lack of regulatory control that would help to differentiate evidence from nonevidence-based aesthetic procedures and appropriate training and accreditation regulations. All these factors lead to consumer-driven medicine.Consumer-driven medicine is often industry-driven medicine with a strong motivation for profit which, in turn, leads to questionable practices and infringement of medical ethics. It is often media-driven medicine because the media benefits from consumption by serving as the vehicle of advertising. Advertising encourages needless consumption that may lead to unethical promotions.Increased demand for aesthetic procedures has resulted in an ever-increasing number of beauty parlour and charlatans providing scientifically unproven aesthetic services and making unproven claims. There is also an increased interest among medical/dental practitioners offering aesthetic procedures for which they were never trained during their medical training, and a confused public who will not be able to distinguish a medically trained aesthetic physician from one who is not.This confused public is beginning to lose confidence and trust in the medical profession because some practitioners are offering nonevidence-based aesthetic treatments and merge their treatments with those offered by beauticians and participate with media to promote their treatments, thereby trivializing and commercializing medical services. These commercialized services tend to falsely promote such procedures as having low/no risk, omitting side effects, exaggerating benefits, exaggerating the indications rather than than the limitations of the treatments, overstating good results and hiding complications and poor responses, and tending to make unsubstantiated claims of superiority. This has been referred to as the invisible hand of the marketing department.The medical fraternity has been traditionally regarded as a credible and trustworthy profession that has typically abided by the time - honored Hippocratic Oath. The advice and services offered by medical professionals are often taken seriously with the belief that doctors will always provide scientifically proven and effective procedures. Their medical training and government regulations in most countries often ensure that the profession maintains a high standard of practice.The public generally trusts medical practitioners to carry out aesthetic procedures rather than to leave it to an untrained beautician. Thus, medical practitioners are attracted by the fairly lucrative and easy way to make a living than to practice conventional medicine. These factors have inevitably driven medical practitioners of diverse specialities into providing aesthetic services. We know that aesthetic medicine, as it is promoted today, generally does not have strong evidence-based rigor in many of the procedures offered. There is a large gap between evidence and practice. There is a tendency for practitioners of aesthetic medicine to move away from science to quackery. This has led to loss of objectivity and of the conventional professional pursuit of excellence which is expected in the practice of medicine.The problem is further compounded by the fact that, at the moment, there are no hard-and-fast rules governing the way aesthetic procedures like botulinum toxin injections are carried out or promoted. Patient safety is left to the discretion of individual doctors.In many countries, there is no proper accreditation process to regulate the practice of aesthetic medicine. Many aesthetic practitioners are not adequately trained to carry out aesthetic procedures. This has resulted in patients complaining against medical practitioners. The practice of aesthetic medicine should not be exempted from the need for structured training and accreditation. This ultimately serves to protect the public from unproven and unsafe treatments. Leaving the aesthetic medicine industry to regulate itself is not a feasible solution as professional and ethical standards in an unregulated industry might take a hit in this lucrative business.In Singapore, the Singapore Medical Council (SMC) Ethical Code and Ethical Guidelines require doctors to treat patients according to generally accepted methods. A doctor shall not offer to patients, management plans or remedies that are not generally accepted by the profession, except in the context of a formal and approved clinical trial. The guiding principles in any medical treatment must be that it is effective and that due cognizance will be given to patient safety. In the context of aesthetic practice, it must go beyond the "Do No Harm" principle and must be seen to benefit the patient positively.no treatment is completely successful as none are more than mildly and temporarily effective." However, despite the lack of evidence to support efficacy, treatment options continue to proliferate for treating cellulite.[There are many examples to quote to confirm that this principle is often not practiced in aesthetic medicine. For example, one report on the treatment of cellulite with noninvasive devices including massage, radiofrequency, mesotherapy, carboxy therapy etc concluded that "… ellulite.despite the increasing interest in mesotherapy as an alternative method for body contouring, there are few reports of its safety, efficacy, and mechanism of action." Their study on the efficacy of mesotherapy for body contouring concluded that mesotherapy is not an effective alternative treatment modality for body contouring.[Another report on mesotherapy stated "…ntouring.There is a need to implement guiding principles on the practice of aesthetic medicine by the medical profession. Evidence-based practice is probably the best approach. As per the SMC Ethical Code and Ethical Guidelines, doctors are responsible for ensuring that they are competent and adequately trained before performing any treatment or procedure on a patient. He or she should keep abreast of medical knowledge relevant to practice and ensure that clinical and technical skills are maintained. The guiding principles in any medical treatment must be that it is effective and there is due cognizance given to patient safety."the conscientious, explicit and judicious use of current best evidence about the care of individual patients".[Evidence-based medicine (EBM) is defined as atients"."conscientious" which signifies an active process which requires learning, practice, and reflection; "explicit" which describes it as a transparent process used to practice EBM; "current" reflecting being up to date, and "best" which signifies that one should seek the most reliable evidence source to inform practice.The keywords in the definition are EBM is a way of thinking and working with the sole objective of ensuring improved health of our patients. The term, "evidence-based practice" is often used instead of EBM and is defined as integrating one's clinical expertise with the best external evidence from systematic research.more rather than fewer treatment options. It is estimated that to keep up with the best evidence available; a general physician would have to examine many journal articles daily and throughout his/her life. The trick is to know how to find information efficiently, appraise it critically, and use it well. The techniques and skills needed to find, critically appraise, and use the best evidence available for the care of individual patients, have been developed over two centuries. These techniques and skills are currently best known as EBM.It should be noted that "therapeutic guidelines" are not the same as EBM. Many dermatology guidelines now incorporate a grading system that describes the quality of evidence used to make recommendations and describe their strength. Searching for relevant information for your patients frequently opens up Asking an answerable structured question generated from a patient encounter.Searching for valid external evidence.Critically appraising the evidence for relevance and validity based on heirarchy of strength in descending order, namely,Systematic reviews and meta-analyses of randomized controlled trialsRandomized controlled trialsNonrandomized intervention studiesObservational studiesNonexperimental studiesExpert opinion4.Applying the results of that appraisal of evidence back to the patient.5.Recording the information for the future.Two filters need to be applied if one is to keep practicing EBM: The first is to discard irrelevant information, and the second is to spend more time looking at a few high-quality papers, as per the concept of hierarchy of evidence.Suzanne Fletcher and Dave Sackett described "levels of evidence" for ranking the validity of evidence about the value of preventive maneuvers, and then assigned them as "grades of recommendations".www.cebm.net/levels_of_evidence.asp). Levels of evidence are based on study design and the methodological quality of individual studies. Grades of recommendation are based on the strength of supporting evidence, taking into account its overall level and the considered judgment of the guideline developers.[Modifications of the above system have been proposed over the last few years. But basically, all utilize levels of evidence and grades of recommendation , an international voluntary group of reviewers and researchers from a range of professional backgrounds dedicated to producing systematic reviews, was established in 1992. In December 1997, a Cochrane Skin Group was registered with the Cochrane Collaboration to prepare, maintain, and disseminate reviews on the effects of health care for people with dermatological conditions.The Cochrane Collaboration (The Group has to produce the best evidence about the effects (good or harm) of health care interventions for dermatological diseases. The scope of the Group includes any dermatological problem that leads a person to seek help from a health care practitioner. The GrouCochrane Library (www.cochranelibrary.com).The Cochrane review is systematic, structured, and painstakingly assembled; it minimizes bias and ensures quality. Whenever possible, Cochrane reviews are based only on RCTs because of the major biases associated with other study designs for assessing treatment effects. After approval according to the internal and external refereeing procedures of the Group, the review is published in the A useful source for evidence-based dermatology reports can be found in the Cochrane Skin Group review wherein specific reports on treatment and other studies are collated and analyzed based on the strengths of the reports. Examples of such Cochrane reports are:"some treatments lead to temporary short-term hair removal. High quality research is needed on the effect of laser and photoepilation".Laser and photoepilation for unwanted hair growth reported by M. Haedersdal and P.C. Gøtzsche. The authors' conclusion was, "the lack of good-quality evidence does not enable any conclusions to be drawn about the effectiveness of lasers for treating atrophic or ice-pick acne scars. Well designed, randomized, controlled comparisons of carbon dioxide versus Erbium:YAG laser are urgently needed."Laser resurfacing for facial acne scars reported by Jordan R.E., Cummins C.L., Burls A.J.E., Seukeran D.C. The authors' conclusions were, All we can do is our best: give the advice, but alert the advisees to the flaws in the evidence on which it is based.On 1 November 2008, the SMC introduced its guidelines on the practice of aesthetic procedures for Singapore medical practitioners. Aesthetic procedures were classified based on currently available scientific evidence and administratively into List A and List B.List A: where there is moderate to high level of evidence and/or with local medical expert consensus that the procedure is well-established and acceptableList B: where there is low or very low level of evidence and/or with local medical expert consensus that the procedure is neither well-established nor acceptableMedical practitioners who wish to perform aesthetic procedures in List A should submit a List A notification form (together with copies of certificates of training) to the SMC's Aesthetic Procedure Oversight Committee (APOC) for verification as to whether it could be considered a Certificate of Competence (COC).Aesthetic procedures under List B are currently regarded as having low or very low level of evidence and are not considered as being well-established. Medical practitioners who wish to perform List B aesthetic procedures should list themselves with the SMC's APOC using a prescribed List B notification form before carrying out any List B aesthetic procedure. Doctors may be subject to audit and should comply with requirements set by the SMC's APOC and the Ministry of Health. Proper documentation of the indications and outcomes of the treatments and procedures are of utmost importance.Medical practitioners who wish to perform procedures that fall within the definition of Aesthetic Practice in the guidelines but which are not found in either List A or List B, will also have to list themselves with the SMC's APOC. The APOC may then decide on the classification of the procedure or further dictate how the doctor should proceed. It is recommended that medical practitioners should not practice such procedures until they have been classified by the SMC's APOC.This list reflects the aesthetic treatments and procedures that are supported by moderate to high level of scientific evidence and/or have local medical expert consensus that the procedures are well-established and acceptable. They are grouped into noninvasive, minimally invasive, and invasive .List B contains aesthetic treatments and procedures that are currently regarded as having low/very low level of evidence and/or being neither well established nor acceptable currently. These are:MesotherapyCarboxytherapyMicroneedling dermarollerSkin whitening injectionsStem cell activator protein for skin rejuvenatione.g., Vacustyler™)Negative pressure procedures Mechanized massage  must be terminated.The patients must not be charged highly profitable fees for such procedures of low evidence, but a fair fee representing the cost of the procedures plus the cost of providing and administering them. Financial documents relating to these procedures must also be retained for the purpose of audit when required. No medical practitioner shall advertise that he or she is performing aesthetic procedures in List B.Any medical practitioner who performs any aesthetic procedure that is not in accordance with these guidelines or with any requirements set by the SMC or MOH will be deemed by the medical profession as being unethical and bringing disrepute to the profession. Such a doctor may be liable for disciplinary action by the SMC.


Evidence is necessary but not sufficient for decision-making, such as making recommendations by clinical practice guideline panels. However, the fundamental premise of evidence-based medicine (EBM) rests on the assumed link between the quality of evidence and "truth" and/or correctness in making guideline recommendations. If this assumption is accurate, then the quality of evidence ought to play a key role in making guideline recommendations. Surprisingly, and despite the widespread penetration of EBM in health care, there has been no empirical research to date investigating the impact of quality of evidence on the strength of recommendations made by guidelines panels.The American Association of Blood Banking (AABB) has recently convened a 12 member panel to develop clinical practice guidelines (CPG) for the use of fresh-frozen plasma (FFP) for 6 different clinical indications. The panel was instructed that 4 factors should play a role in making recommendation: quality of evidence, uncertainty about the balance between desirable (benefits) and undesirable effects (harms), uncertainty or variability in values and preferences, and uncertainty about whether the intervention represents a wise use of resources (costs). Each member of the panel was asked to make his/her final judgments on the strength of recommendation and the overall quality of the body of evidence. "Voting" was anonymous and was based on the use of GRADE  system, which clearly distinguishes between quality of evidence and strength of recommendations.Despite the fact that many factors play role in formulating CPG recommendations, we show that when the quality of evidence is higher, the probability of making a strong recommendation for or against an intervention dramatically increases. Probability of making strong recommendation was 62% when evidence is "moderate", while it was only 23% and 13% when evidence was "low" or "very low", respectively.We report the first empirical evaluation of the relationship between quality of evidence pertinent to a clinical question and strength of the corresponding guideline recommendations. Understanding the relationship between quality of evidence and probability of making (strong) recommendation has profound implications for the science of quality measurement in health care. Evidence is necessary but not sufficient for decision-making, such as making recommendations by clinical practice guideline (CPG) panels . Indeed,The American Association of Blood Banking (AABB) has recently convened a panel to develop CPG for the use of fresh-frozen plasma (FFP) for 6 different clinical indications (manuscripts in preparation). The panel decided to employ the GRADE method,5 to devGRADE's fundamental premise is that the CPG should be based on systematic review (SR) of evidence, i.e. a SR of the totality of relevant highest quality research evidence represents a scientific foundation for development of clinical practice guidelines. The AABquality of evidence is rated as:According to the GRADE system, High: Considerable confidence in the estimate of effect. Future research is unlikely to change the estimate of the health intervention's effect.• Moderate: Further research is likely to have an important impact on confidence in the estimate, and may change the estimate of the health intervention's effect.•Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.•Very low: Any estimate of effect is very uncertain.•strength of recommendations (for or against intervention) is graded as strong (indicating judgment that most well informed people will make the same choice), weak , or uncertain (indicating that the panel made no specific recommendation for or against interventions). The panel was instructed that 4 factors should play a role in making recommendation: quality of evidence, uncertainty about the balance between desirable (benefits) and undesirable effects (harms), uncertainty or variability in values and preferences, and practice setting/uncertainty about whether the intervention represents a wise use of resources (costs)[The s (costs). That isEach member of the panel was asked to make his/her final judgments on the strength of recommendation and the overall quality of the body of evidence. "Voting" was anonymous and were based on the use of GRADE grids for formulation of the strength of recommendations, weak ("for" or "against") and "uncertain". Quality (as determined by each panel member) was entered as a categorical outcome . Since "voting" on separate questions by the same member of the panel was likely not independent, we employed a hierarchical, multi-level analysis to analyze the relationship between quality of evidence and the strength of recommendations.We analyzed the relationship between quality of evidence and the strength of recommendations using a proportional odds model (cumulative logistic model), an extension of logistic regression to handle ordinal response variables. We assessed model fit using a likelihood ratio test (comparing versus an intercept-only model). We asserted that the proportionality of odds assumption was not violated using the score test. The proportional odds model treats all observations as independent, but "votes" on separate questions by the same member of the panel were likely not independent. We explored whether this had any effect by fitting models that allow non-independent observations. Specifically, we fitted a generalized linear mixed model with a cumulative logistic link function and the panel member as the clustering variable, and an additional model using generalized estimating equations. Because the results from the more complicated models were identical with these of the aforementioned simple analysis, we present findings from the ordinal logistic regression (most parsimonious model). Finally, in exploratory analyses we treated the quality ratings given by the panel members as a continuous variable and extrapolated what the predicted probabilities for an uncertain, weak or strong recommendation would be for "high" quality evidence.gllamm program in Stata SE 9.2[All analyses were performed using the Table In the cumulative logistic model, the odds ratio for stronger recommendations  was 2.06  when the quality of evidence was "low" rather than "very low". The corresponding odds ratio was 11.30  when the quality of the evidence was "moderate" rather than "very low". Overall, quality was associated with the strength of recommendation beyond chance . The assumption of proportionality of odds was not violated .To facilitate the interpretation of these results, Figure In exploratory analyses, treating quality as a continuous variable resulted in qualitatively similar estimates. Extrapolating to a hypothetical instance of "high" quality evidence, the predicted probabilities for "strong", "weak" or "uncertain" recommendation was 77.2, 20.2 or 2.6 percent, respectively.Many factors play a role in making recommendations. As explained above, the GRADE method, which we used to develop the FFP transfusion guidelines, stresses the importance of 4 factors in formulating guideline recommendations: quality of evidence, trade-off between benefits and harms, patient values and preferences, and use of resources. NevertheWe note with interest that despite the central role that evidence plays in EBM movement, our study is the first empirical study that researched the role of evidence in making guidelines recommendations. The only other study that indirectly investigated a similar issue is one by Cruse et al. These iOur study does have some limitations: 1) our study was based on the example from one guideline only (AABB). While we believe that the results from studying other guidelines panels would likely be similar as long these panels use GRADE method, this conjecture remains to be confirmed. 2) the panel members' quality assessment were likely influenced by the quality ratings provided in the SR originally prepared to facilitate developing guidelines recommendations. This quality rating, however, was related to the quality of evidence for each relevant outcome that was analyzed in SR. The panel, on the other hand, rated the quality of the entire body of evidence across all outcomes. Indeed, the fact that the quality rating by 12 members of the panel was not uniform for any of 6 recommendations indicates that each member of the panel was making his/her independent judgments about the overall quality of evidence; 3) we did not collect data on other dimensions of importance for making recommendations such as judgments about trade-offs between benefits and harms, use of resources and patients values and preferences. Although these factors, particularly judgments on trade-off between benefits and harms and use of resources have undoubtedly influenced each member's deliberation, we believe that our results appear to demonstrate that the quality of evidence is likely to be a key factor underlying the strength of the panel's recommendation. 4) due to small sample size (72 observations) and the lack of data on high-quality evidence, we could not establish a more accurate relationship between high quality evidence and strength of recommendations. For 3 categories of data that are related to the quality of evidence  and strength of recommendation  our model assumed a linear relationship. A positive relationship exists between the quality of evidence  and strength of recommendation . Score test shows the proportional odds assumption that cumulative logit model required is satisfied. However, if we were to have data on the "high" quality category, the relationship may change. In fact, decades of research in psychology and economics show that people's perceptions and judgments are not linearly related. . The samUnderstanding a relationship between quality of evidence and probability of making (strong) recommendation is important and has profound implications for the science of quality measurements in health care. For example, the GRADE group recommends that adherence to strong recommendations can be used as a quality criterion or performance indicator. We discuThe current work provides an empirical demonstration of the strong link between good quality evidence and decision-making. Because only strong guideline recommendations can be used as performance measures or healthcare quality indicators, it is imperative to design, fund and conduct pragmatic studies that are resistant to internal and external biases. This would ideally generate credible evidence base that will uniformly (close to 100%) be associated with strong recommendations. Thus, efforts to develop performance measures based upon existing research should focus mainly on areas with good quality evidence. Additional research is clearly indicated to establish the true pattern between quality of evidence and strengths of recommendations.The authors declare that they have no competing interests.BD conceptualized the study, performed initial analyses and wrote the first draft of the manuscript. TT and RC performed additional statistical analyses. JR organized AABB guidelines panel and enabled the survey. GG advised on the use and interpretation of the GRADE system. All authors helped interpreted results and edited it for the intellectual content.The pre-publication history for this paper can be accessed here:Summary of the AABB (American Association of Blood Banking) panel members vote on the use of FFP (fresh-frozen plasma)for 6 different clinical indications. a distribution of the AABB (American Association of Blood Banking) panel members vote related to the quality of evidence and the strength of recommendations for the use of fresh-frozen plasma for 6 different clinical indications.Click here for file


Few methodological studies address the prioritization of clinical topics for the development of Clinical Practice Guidelines (CPGs). The aim of this study was to validate a methodology for Priority Determination of Topics (PDT) of CPGs.Firstly, we developed an instrument for PDT with 41 criteria that were grouped under 10 domains, based on a comprehensive systematic search. Secondly, we performed a survey of stakeholders involved in CPGs development, and end users of guidelines, using the instrument. Thirdly, a pilot testing of the PDT procedure was performed in order to choose 10 guideline topics among 34 proposed projects; using a multi-criteria analysis approach, we validated a mechanism that followed five stages: determination of the composition of groups, item/domain scoring, weights determination, quality of the information used to support judgments, and finally, topic selection. Participants first scored the importance of each domain, after which four different weighting procedures were calculated (including the survey results). The process of weighting was determined by correlating the data between them. We also reported the quality of evidence used for PDT. Finally, we provided a qualitative analysis of the process. The main domains used to support judgement, having higher quality scores and weightings, were feasibility, disease burden, implementation and information needs. Other important domains such as user preferences, adverse events, potential for health promotion, social effects, and economic impact had lower relevance for clinicians. Criteria for prioritization were mainly judged through professional experience, while good quality information was only used in 15% of cases.The main advantages of the proposed methodology are supported by the use of a systematic approach to identify, score and weight guideline topics selection, limiting or exposing the influence of personal biases. However, the methodology was complex and included a number of quantitative and qualitative approaches reflecting the difficulties of the prioritization process. The need to set priorities for developing Clinical Practice Guidelines (CPGs) has been recognized by several CPG developers, in part due to the rapid development of medical technology and finite resources of organizations ,2. AlthoPrioritization to Determine Topics (PDT) for CPGs is frequently influenced by the availability of human and financial resources. PDT also varies according to specific needs of sponsors, such as health care organizations and the different hierarchical levels within the health research system ,4. A metWe used an explicit methodology to prioritize topics for CPGs in order to evaluate the topics identified with this methodology and see if they were, in fact, considered high priority.The primary aim of this study was to develop and validate an explicit methodology for PDT of CPGs within the setting of a developing country. We used a number of different approaches to develop and assess the PDT process: instrument development; an external survey; a pilot testing of the PDT procedure and; a qualitative evaluation. The PDT procedure integrated quantitative and qualitative data from different sources. A summary of the stages of the PDT procedure as well as the methodological approaches used for validating the process are shows in Figure We developed a formal instrument for prioritizing guideline topics with the following characteristics: domain/criteria importance; quality of the supporting evidence for scoring each domain; availability of supporting bibliography; additional domains or criteria not listed in the tool.http://www.nice.org.uk, the Scottish Intercollegiate Guidelines Network http://www.sign.ac.uk, the World Health Organization , the New Zealand Guidelines Group http://www.nzgg.org.nz/, The Canadian Medical Association InfoBase, Guidelines Advisory Committee http://www.gacguidelines.ca/ National Guideline Clearinghouse http://www.guideline.gov/resources/guideline_resources.aspx, and the G-I-N database http://www.g-i-n.net. The search included observational, descriptive, comparative, interventional studies and reports published in CPG clearinghouses. A number of reports were identified and analyzed  using the methods described by Kraemer ) OR (priorit* strateg* [tw])).The authors declare that they have no competing interests.LGC has contributed to this study in a personal capacity and in his spare time. The Pan American Health Organization (PAHO) does not assume responsibility for the statements contained therein.All authors participated in the design of the study, in addition to reading and approving the final manuscript. LR, JSC and DT conceived the study, and participated in its design and coordination and draft the manuscript. JSC performed the statistical analysis. MT, PM, PO, DT, LGC and RP helped to draft the manuscript. All authors read and approved the final manuscript.Instrument for prioritizing guideline topics. the instrument includes characteristics such as the domain/criteria importance; the quality of the supporting evidence for scoring each domain; the availability of supporting bibliography.Click here for file


The ideology of evidence-base medicine (EBM) has dramatically altered the way we think, conceptualize, philosophize and practice medicine. One of its major pillars is the appraisal and classification of evidence. Although important and beneficial, this process currently lacks detail and is in need of reform. In particular, it largely focuses on three key dimensions  to grade the quality of evidence and often omits other crucial aspects of evidence such as biological plausibility, reproducibility, generalizability, temporality, consistency and coherence. It also over-values the randomized trial and meta-analytical techniques, discounts the biasing effect of single centre execution and gives insufficient weight to large and detailed observational studies. Unless these aspects are progressively included into systems for grading, evaluating and classifying evidence and duly empirically assessed (according to the EBM paradigm), the EBM process and movement will remain open to criticism of being more evidence-biased than evidence-based."All scientific work is incomplete – whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time".Sir Bradford Austin Hill  The widespread acceptance of the principles of Evidence-Based Medicine (EBM) have generated a significant paradigm shift in clinical practice, medical education and in how studies are designed, reported, appraised and classified ,3. The gIn this commentary, we will argue that the present system(s) for classifying the quality of evidence and subsequent formulation of graded recommendations would benefit from reform. A reformed method for classifying evidence should integrate additional dimensions of evidence not traditionally considered, as well as incorporate a method of assigning weight to each dimension when determining the overall quality of the evidence. In this context, we will further comment on the newly proposed hierarchal system, the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system, for gauging the quality of evidence and strength of recommendations from research evidence . The objIdeally, physicians would be able to predict the biological future and clinical outcome of their patients with unbiased certainty and naturally use this knowledge in their care. As an example, physicians would know that the early administration of tissue plasminogen activator (tPA) to a patient with acute massive pulmonary embolism would lead to survival where other interventions would not . MoreoveRegrettably, we cannot predict the biological and clinical future with such certainty. Rather, the physician can only be partly reassured by knowing "the operative truth" for questions about this intervention: What would result if all such patients with massive pulmonary embolism were randomly allocated to receive either tPA or an alternative treatment? Would one intervention significantly increase survival over the other? By what magnitude would survival increase? How would such an increase in survival weigh against the potential harms? The physician could then apply knowledge of the "operative truth" about such interventions to guide the course of patient care.Yet again, such truth in absolute terms is unknown. Rather, physicians are dependent upon estimation and/or measures of probability of the truth for predicting the biological and clinical future of interventions. Naturally, we obtain and apply estimates of the effects of an intervention through the generation of "evidence".Evidence, can be derived from a multitude of sources: from personal experience, teaching by mentors, local practice patterns, anecdotes, case series, retrospective accounts, prospective observations, non-interventional controlled observations, before-and-after studies, single centre randomized evaluations, randomized evaluation in multiple centres in one or more countries to blinded randomized multi-centre multi-national studies. The evidence generated in each of these forms has both merits and shortcomings. Nonetheless, the focus of this discussion is an examination of how the medical community currently formally appraises, classifies and grades the various forms of evidence.The process of understanding how new, evolving or "best evidence" is translated into knowledge integrated into patient care remains a great challenge ,10. All The "evidence hierarchy" should emphasize that evidence exists on a continuum of quality. Simply, the evidence generated from some study designs is logically more prone to bias than other designs and, as a consequence, has traditionally provided a weaker justification for influencing clinical practice . UnfortuThe apex of the pyramid of evidence has generally been considered the well-conducted and suitably-powered multi-centre multi-national blinded placebo-controlled randomized trial. Such a trial would be characterized by demonstration that intervention X administered to patients with condition A leads to a significant improvement in a clinically-relevant and patient-centred outcome , when compared to placebo, assuming a genuine and plausible treatment effect of intervention X.Yet, there may be circumstances where a strong recommendation may not be appropriate for such a trial. This may occur when an intervention does not lead to or is not correlated with improvements in a clinically-relevant patient-centred outcome, when a trial employs, as a primary outcome, a surrogate measure  or when the apparent harm related to an intervention outweighs the benefit. Under these conditions, a lower grade of evidence may be assigned (i.e. Grade B).By all current evidence hierarchies, this would be considered as level I evidence that intervention X works for condition A. Table  These fiIn the absence of suitably-powered multi-centre multi-national blinded placebo-controlled randomized trials, many would also regard a high-quality systematic review as level I evidence. Yet, systematic reviews require vigilant interpretation and should not necessarily be considered as high level evidence due to issues related to poor quality, incomplete reporting and the inclusion of evidence from trials of poor quality ,15. We cThis archetypal hierarchal system would appear reasonable and not in need of reform. Yet, we also contend that traditional hierarchal systems have broadly focused on only three dimensions for defining, classifying and ranking evidence: study design; probability of an alpha or type-I error; and probability of beta or type-II error. We consider these fundamental aspects of trial design for evidence hierarchies below and further discuss a recent initiative (the GRADE system) to improve and standardize how evidence generated from clinical research is classified and graded. Before embarking upon a detailed discussion of the tools used to assess the quality of evidence, we wish to emphasize that no EBM tool can be possibly expected to answer all questions related to evidence. We further notice that a good randomized controlled trial is neither necessary nor sufficient to change practice. However, as we argue below, both are perfectible in specific directions.[An updated scheme for grading the quality of evidence and strength of recommendations has been developed by the GRADE Working Group ,12,18,19The GRADE system defines the "quality of evidence" as the amount of confidence that a physician may have that an estimate of effect from research evidence is in fact correct for both beneficial and harmful outcomes . A globaThe "strength of a recommendation" is then defined as the extent in which a clinician can be confident that adherence to the recommendation will result in greater benefit than harm for a patient . Further). Yet, we believe there remain elements of evidence from research that have not been explicitly addressed in the GRADE system and require further consideration and debate as discussed below.The GRADE system represents a considerable improvement from the traditional hierarchies of grading the quality of evidence and strength of recommendations and has now been endorsed widely by a spectrum of organizations and societies . This philosophical stance assumes that the randomized controlled trial represents the "gold standard" as the most scientific and rigorous study design available . AccordiFirst, as an example, in the ARDS Network trial evaluating the impact of low tidal volume ventilation in critically ill patients with acute respiratory distress syndrome (ARDS) on mortality, it now appears that, in the study centers, not all patients allocated to the control group were given a current or near-current accepted therapy or standard of practice. Second, this pivotal trial cannot be easily classified according to the GRADE tool. It is unclear how one can classify trials that assess the implementation of protocols or changes in process of care, which, cannot be blinded . DespiteSecond, how can we classify, categorize and compare trials of surgical interventions or devices , high-frequency oscillatory ventilation (HFOV), continuous renal replacement therapy (CRRT)) where true blinding is impossible ? FinallyWe contend these questions suggest a need for further refinement of how we classify the quality of evidence according to study design. At minimum, this should include principles on how to classify device and "bundle of care" trials and how to incorporate a provision that demonstrates that, as a minimum, the control arm received "standard therapy" .A Type I or alpha error describes the probability that a trial would, by chance, find a positive result for an intervention (i.e. effective) when, in fact, it is not  and represent a chance or statistical error. In general, the alpha value for any given trial has traditionally and somewhat arbitrary been set at < 0.05. While recent trends have brought greater recognition for hypothesis testing by use of confidence intervals, the use of an alpha value remains common for statistical purposes and sample size estimation in trial design.The possibility of a type I error is generally inversely related to study sample size. Thus, a study with a small sample size or relatively small imbalances across allocated groups or in the context of numerous interim analyses might be sufficient, alone or together, to lead to detectable differences in outcome not attributable to the intervention. Likewise, a trial with few observed outcome events, often resulting in wide confidence limits around an effect estimate, will potentially be prone to such an error.The potential bias due to type I errors can be recognized by evaluation of key aspects of the study design and findings. These include whether the trial employed a patient-centred or surrogate measure as the primary outcome, evaluation of the strength of association between the intervention and primary outcome (i.e. relative risk or odds ratio), assessment of the precision around the effect estimate (i.e. confidence limits), and a determination of the baseline or control group observed event rate. Level I evidence mandates that trials have a low probability of committing a type I error. While desirable, how do we clinically or statistically measure a given trial's probability of type I error? Should we adjust the statistical significance of an intervention found in a clinical trial to the probability of a type I error? These questions suggest a need for both discussion and consensus on the concept of alpha error and its practical application. This discussion has not formally taken place in the literature.A type II or beta error describes a statistical error where a trial would find that an intervention is negative (i.e. not effective) when, in fact, it is not . An increase in sample size and the number of observed outcome events reduce the probability a type II error, on the assumption that a genuine difference in effect exists across the allocated groups. Thus, to minimize the chance of a type II error, clinical trials must be suitably "powered". In general, the probability of type II error is conventionally and arbitrarily set at 0.10–0.20 (i.e. power 0.80–0.90). The calculation of power is used in study design to determine and justify the overall sample size. Inadequately powered trials risk missing small but potentially important clinically differences in outcome attributable to the intervention under assessment ,27. NatuGiven these implications, should attaining suitable power for a trial simply be a matter of statistical consideration? Can we standardize what suitable power represents for a given intervention? Should we subject suitable power in trial design to additional public health considerations such as: the size of the population likely to benefit from the intervention if proven effective; the clinical relevance of the outcome being assessed; and the potential downstream cost of integrating the intervention in clinical practice? We also contend that these issues warrant consideration in the context of trials of equivalency or non-superiority and more specifically for trials that are pre-maturely terminated at interim analyses -31. Finasine qua non". Above, we considered and discussed the limitations of several traditional measures to evaluate the quality of evidence, in particular with a focus on what EBM considers the "old standard" – randomized trials. Below, we contend that there are additional dimensions to evidence that merit attention, both for randomized trials and epidemiologic studies, when appraising, classifying and grading the quality of evidence. Moreover, many of these dimensions take into account the issues identified by Hill when deciding whether an observed association was a causal relationship.In 1965, Sir Austin Bradford Hill described nine issues he considered important, in a Presidential Address to the Section of Occupation Medicine of the Royal Society of Medicine, for potentially inferring causation from statistical associations observed in epidemiology data [in vitro studies, experimental data, epidemiologic investigations and additional randomized trials. In fact, there may be circumstances for which randomized trials are unnecessary (i.e. due to obvious and large treatment effect), or more importantly, unethical [Evidence from randomized trials does not and cannot stand on its own, independent of previous information or studies. As discussed previously, prior knowledge can be accrued from a variety of sources ranging from personal experience to nethical ,21. For nethical ,33. AccoMore recently, there have been high profile examples of large epidemiologic studies (phase IV studies) of interventions showing previously unknown potential harm -38. Thistoo large to be clinically possible, and lacked biological plausibility and coherence. Accordingly, the committee recommended the trial be continued and the final results (no difference between the two therapies) vindicated this apparent chance finding at interim analysis [We believe this dimension, along with issues of temporality and coherence, should be more formally acknowledged in a reformed classification system. We similarly believe that careful attention must be paid to robust findings which contradict current beliefs and concepts of what is biologically plausible.These issues were central to Hill's viewpoints and, while seemingly obvious, are in fact not always evident. For example, most, perhaps all, reasonable clinicians would reject the findings of a randomized trial of retroactive intercessory prayer compared with usual care showing a statistically significant decrease in the duration of hospital stay in patients with septicemia . Such a analysis . These eConsistency in evidence refers to finding reproducibility in the effect of an intervention in numerous studies and across diverse populations, settings, and time. For example, the PROWESS trial tested the efficacy of rhAPC in severe sepsis, however, it was limited in scope by the study inclusion criteria  . Yet, thLikewise, "complex interventions" which involve devices, therapies, protocols or processes  pose major challenges for researchers ,32. The We consider that a formal grading of applicability is needed in future classifications of evidence.We contend that due thought needs to be given to how the results of a trial can be translated into interventions that reliably work, are reproducible, are broadly applicable and can be applied elsewhere. The GRADE system does incorporate a subjective assessment of consistency as criteria for grading the quality of evidence and, in the setting of unexplained heterogeneity across trials, suggests a decrease in grade . We consThe generalizability of findings from a clinical trial represents a fundamental dimension of evidence, that of external validity. Narrow controls designed to optimize the internal validity of a trial  can compete with and compromise overall generalizability ,52. WhetHow generalizable are the findings of a single centre study, however well designed? Should single centre trials ever lead to level I evidence or grade A recommendations? Accordingly, how should we classify the evidence from a single centre trial showing benefit? For example, would early goal-directed resuscitation really improve the outcome of all patients with septic shock presenting to Emergency Departments worldwide or do the findings of this trial simply reflect improvements in patient care in a single institution where there existed a very high pre-intervention mortality ? These aIn the end, there needs to be a greater understanding and consensus around the limitations of data from single centre studies. We need to consider the meaning of multi-centre and how it relates to grading the quality of evidence. Additionally, we need to consider and discuss the implications of multi-centre studies sponsored by industry that evaluate new pharmaceutical interventions. We also need to relate the control population studied in any single or multi-centre trial to other large populations with respect to the same condition, so that we can consider the "generalizability level" of a given study.) arose from observational data and were missed in single centre studies [Importantly, we also need to give a greater consideration to the weight of evidence from observational studies in the context of the known limitations of randomized trials ,55,56. W studies ,38,57,58 studies . The rec studies .While there are obvious differences in study design, well-performed observational studies may provide a powerful mechanism to improve the generalizability of evidence and may well provide more robust evidence than single centre randomized controlled trials ,56,61,62An argument can be made that proposed classification schemes, especially the new GRADE system, are best left alone. They are reasonably simple, explicit, have been validated and now are increasingly endorsed. Furthermore, the additional dimensions of evidence we have discussed  are often difficult to simply measure and their impact on how the findings of an individual trial approximate the "truth" is hard to quantify. Table  On the oA classification system which is simple is indeed desirable but becomes a problem when, for the sake of simplicity, it fails to take into account important aspects of the growing complexity of the evidence available. Accordingly, summary classifications of the quality of evidence and strength of recommendations, such as the GRADE system, will continue to have an important and expanding role in medicine. We believe that as the GRADE system becomes more widely endorsed, additional refinements to the system will result in appropriate recognition of higher quality evidence and contribute to greater confidence in recommendations for clinical practice. We also believe that this field is very much "work in progress" and needs to evolve more explicit recognition and classification of the dimensions of trial design discussed in this manuscript.In this commentary, we have argued in favour of the concept that assessing of the quality and strength of evidence from clinical studies requires reform. Such reform should, in particular, reflect those dimensions of evidence, which are currently not routinely or explicitly addressed. The GRADE Working Group has made considerable contributions to improving how the quality of research evidence and recommendations are graded. We believe that additional reform is needed to explicitly address and quantify dimensions of evidence such as biological plausibility, reproducibility, temporality, consistency, ability to detect harm and generalizability. We also believe that observational studies need to be graded and that, under some circumstances, such studies provide either evidence that cannot be detected in single centre studies or even better evidence than produced from small, randomised trials. We believe such reform should occur through consensus. We also believe that such reform will have lasting beneficial effects on clinical practice and on the future design, reporting and assessment of clinical studies.Both authors (SMB and RB) wrote and revised the manuscript. Both authors read and approved the final manuscript.Dr. Sean Bagshaw is an intensivist at the University of Alberta Hospital and an Assistant Professor in the Division of Critical Care Medicine, University of Alberta, Edmonton, Canada. His research interests include acute kidney injury and extracorporeal therapies in critically ill patients, medical emergency/rapid response teams, end-of-life care and clinical trial/meta-analysis methodology.Prof. Rinaldo Bellomo is Professor of Medicine with Melbourne, Monash and Sydney University and Director of Intensive Care Research at the Austin Hospital, Melbourne. He has been on the management committee of all the multicentre randomized controlled trials conducted by the Australian and New Zealand Intensive Care Society Clinical Trials Group .