SEARCH

SEARCH BY CITATION

Keywords:

  • evidence-based medicine;
  • practice guidelines;
  • asthma;
  • rhinitis;
  • Cochrane

Abstract

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References

 Clinical guidelines are ‘systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances’. They may offer concise instructions on which diagnostic or screening tests to order, stipulate how medical services should be provided, how long patients should stay in hospital, or many other details relevant to clinical practice. This paper argues that guidelines should be simple, adapted to the clinical setting they inform and to treatment availability in their respective geographic context and that they should not be viewed as a yardstick but as support for physicians. The benefits of evidence-based-medicine (EBM), which defines the value of medical interventions in terms of empiric evidence from clinical trials, are growing in many contexts and are well described. Not sufficiently acknowledged, however, are the limits of EBM. A gap still exists between clinical research and clinical practice which should be better recognized and assessed.

Clinical guidelines are systematically developed statements designed to help practitioners and patients to make decisions about appropriate health care in specific circumstances (1). Guidelines have covered evidence ranging over many countries and areas of medicine (2) with asthma (3, 4) and allergic rhinitis (5) featuring large among numbers which have run into thousands. Interest for guidelines in recent years has been rekindled as they are being increasingly seen as a tool for implementing health care on the basis of proof of effectiveness. Thus, clinicians are daily overwhelmed by new guidelines and, in addition to this spate of clinical guidelines, a number of ‘guidelines for guidelines’ have also been produced (Table 1). The aim of guidelines is their widest dissemination within the medical community to all health-care professionals and beyond to patients themselves to improve patient care. However, the very real limitations and harms that may result from clinical guidelines should be weighed against their potential benefits (Table 2).

Table 1.  Guidelines for clinical guidelines (adapted from Jackson R, Feder G. Guidelines for clinical guidelines [editorial]. BMJ, 1998;317:427–428.)
Key components of clinical guidelines:
• Identification of the key decisions and their consequences
• Review of relevant, valid evidence on the benefits, risks and costs of alternative decisions
• Presentation of the evidence required to inform key decisions in a simple, accessible flexible format
Table 2.  Opinion-based medicine
Physicians always try to base their decisions on the best available evidence, all too often this evidence represents:
• extrapolations from physiopathology
• conditioning from pre- and postgraduate training, • clinical experience
• logic, rather than established facts

Increasing attention should be paid to the methodology of guideline development and to the validity of their recommendations. While an increasingly rigorous approach is being applied to guideline development, it is important to re-emphasize the central role guidelines themselves should play in helping clinicians inform and improve their decisions. Guidelines which are based on the best available published data are predicated on the opinion of experts which in turn derives from clinical trial evidence or mechanistic experimental approaches. The systematic process of preparing best-research evidence guidelines has become an essential element to the practice of ‘evidence-based-medicine’ (EBM).

EBM is an increasingly important concept in medicine that may eventually become a new paradigm. It is the ability to track down, critically appraise (for its validity and usefulness) and incorporate the information obtained from randomized clinical trials to establish the basis for diagnosis, prognosis, and therapy (6). The increasing influence of EBM is partly the result of the work of the Cochrane Collaboration (7,8). The importance of this organization should be noted even though some criticisms of its role have been voiced (9–13).

Why do we need EBM?

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References

Physicians sometimes question whether EBM is actually ‘worth it’, as if EBM carried the implied reproof that they may have been remiss in some of their ways. Yet the world of medicine is changing rapidly – too rapidly perhaps for long-established habits to paper over all the gaps in our knowledge. Resources are being increasingly downsized at a time when technology grows exponentially while our time, finances and the availability of tests and treatments are no longer expandable. If we are to fight for the best decisions for our patients, we must be prepared to inform our decisions with more than just opinions and anecdotes. Patient values, medical ethics, common sense, or spirituality will not decline because of this; indeed patient-oriented goals may gain in relevance as we are freer to focus on the ‘nonevidence’ aspects of our practice. Physicians always try to ground their decisions on the best evidence available to them. Often this evidence represents extrapolations from physiopathology, clinical experience and logic rather than established facts based on hard data derived from patients (Table 2). For many years, clinicians have had to cope with the accusation that only 10–20% of the treatments they provide have any foundation in scientific fact. Their interventions, in other words, are seldom ‘evidence-based’. It appears however, that many therapeutic decisions are already based on solid evidence (14).

To deal with the rapid evolution of medicine, physicians need to remain abreast of new therapies and diagnostic tools of use in their practice. Unfortunately, along with many changes there will also be found a plethora of relevant published material. Physicians are unable to absorb this mass of information because of time constraints. Instead, they must choose to use this information efficiently.

Importance of EBM in clinical recommendations

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References

The recent proliferation of randomized controlled trials has led to a rapid increase in the quantity and quality of clinically valid evidence in diagnosis and screening, prognosis, therapy, harm and other important health-care issues (6) (Table 3). In the late 1980s clinicians began to draw attention to the often poor scientific quality of health-care review articles. Subsequently, the need for systematic reviews of the effects of health-care interventions became widely recognized and checklists and guidelines were developed (15,16). As a result, it has become possible to make explicit much of the implicit nonverbal reasoning of expert clinicians and to make their clinical reasoning more accessible and comprehensible to all clinicians (6) (Fig. 1). However, meta-analyses should obey certain rules, some of which may not necessarily be self-evident (Table 4).

Table 3.  Evidence-based medicine (adapted from Sackett DL, Rosenberg WM. The need for evidence-based medicine. J R Soc Med. 1995;88:620–624)
An increasingly important concept and a new paradigm in medicine, it comprises the ability to:
• track down, • critically appraise
• analyse randomized clinical trials and meta-analyses
• establish the clinical basis for diagnosis, prognosis and therapy
image

Figure 1. Development of clinical guidelines.

Download figure to PowerPoint

Table 4.  Importance of meta-analyses
• Meta-analyses are essential to critically assess diagnostic or treatment interventions
• Meta-analytic methodology should be optimized to offset criticism of method
• Clinical question(s) should be proposed by an independent expert panel
The conclusions of the meta-analysis:
• should not be proposed only by the authors of the meta-analysis but with the help of an expert panel
• should be formulated within the disease context and against all alternative interventions

EBM attempts to provide a convenient logical framework from which the quality and relevance of clinical studies may be assessed in an unbiased manner (17). The evidence-based approach also allows the reader to discriminate between solid evidence and evidence that is based on a presumed mechanism, standard practice, or on conventional wisdom. EBM, de-emphasizing as it does the reliance on clinical intuition, unsystematic clinical experiments and rationales based on physiopathological assumptions, aims to supply the necessary but sufficient basis for informing and making clinical decisions. It stresses first and foremost the critical examination of evidence from clinical research. Systematic reviews contribute to resolve uncertainty when original research, reviews and editorials are in disagreement (as will often be found) (18). Systematic reviews are particularly useful when there is uncertainty regarding the potential benefits or harm of an intervention (18). EBM applies decision theory and analysis to clinical diagnosis (19) and to the optimal management of disease.

The Cochrane Collaboration has led the way in setting new standards for preparing systematic reviews (7) which are published in electronic format as part of the Cochrane Library. Cochrane reviews are, on average, more systematic and less biased than systematic reviews published in print journals. However, errors and biases also occur in Cochrane reviews (20). All too often, reviewers' conclusions over-rate the benefits of new interventions. Readers of Cochrane reviews should remain cautious, especially regarding conclusions that favour new interventions. However, the Cochrane Collaboration has taken steps to improve the quality of reviews through, for example, more thorough prepublication refereeing, offering training and other support to reviewers and improving the postpublication peer review process (21). In addition, the use of evidence-based criteria (i.e. the QUOROM statement) for reporting systematic reviews may go further towards improving quality (22,23).

There are other drawbacks. Systematic reviews are often criticised for their failure to offer specific guidance. This is often because the primary studies that they analyse contain few assessments of outcome measures (18). It is difficult to find supporting evidence in the case of many clinical management decisions. It may also be difficult to interpret evidence when it is available and applying this evidence to the single patient in the consultation may be even less straightforward. Clinical decisions may be influenced at many levels through health policy, audit, protocols and guidelines, but the individual therapeutic patient–physician relationship remains at the core of medical practice (24,25). Many questions cannot be answered by EBM (26). Thus for some, it remains an imperfect method of informing treatment choices (27) and may even give rise to issues of medical ethics (28).

Moreover, recommendations based on EBM are not always balanced and it seems appropriate to propose recommendations after an expert group has reviewed the evidence and examined it in the context of the disease and of all forms of interventions. One of the major issues about EBM recommendations involves allergen avoidance and asthma. In one such study (29), it was found that house dust mite avoidance measures were ineffective. This study provoked several criticisms (30) and even the accompanying editorial admitted to benefits unproven albeit not to be excluded (31). Subsequent analysis found that the conclusions had to be modified (32). Even currently available evidence from controlled trials of physical and chemical approaches to house dust mite antigen exposure reduction in the homes of mite-sensitive asthmatics does not provide an absolute certainty on which to base advice and policy. Further trials – one of them very large – are currently in progress. The additional evidence from these studies will help to clarify whether or not the substantial efforts required to implement strategies intended to reduce mites can be expected to yield beneficial effects of a magnitude that people with mite-sensitive asthma will consider worthwhile. The results of two large recent trials do not confirm the role of allergen avoidance in either asthma or rhinitis (33,34). These studies exemplify the difficulty inherent to the process of generating valid, generalized conclusions, as new evidence will always come in to update recommendations. In allergy to pets, the available trials are too small to provide evidence for or against the use of air filtration units to reduce allergen levels in the management of pet-allergic asthma. Adequately powered trials are needed. There are no trials of other allergen reduction measures, such as pet washing or, possibly, pet removal (35).

Great progress has been made in obtaining reliable evidence on the beneficial effects of interventions but developments in the identification, interpretation and reporting of harmful effects are still daunting (36,37). There is an urgent need to obtain better-quality evidence from harm studies. Randomized controlled trials are the best way to evaluate the small-to-moderate effects of health-care interventions and much of the evidence on treatment benefits is derived from such studies. However, they are not always suitable to evaluate harm. The debate about the potentially serious cardiovascular effects of cyclooxygenase-2 (COX-2) inhibitors illustrates some of these problems. Serious cardiovascular effects associated with the use of COX-2 inhibitors have recently come to the fore (38) because they were not systematically sought in previous trials (39). The danger therefore is that harmful drugs may continue to be used for many years before a warning is actually raised.

The development of clinical guidelines should follow a strict protocol which is now recognized by several organizations including the World Health Organization (WHO), the National Institutes of Health, the Scottish Intercollegiate Guideline Network (http://www.sign.ac.uk) or the Agence Nationale d'Accréditation et d'Evaluation en Santé (http://www.anaes.fr). An itemized list should be followed and it is only if the recommendation has reached a certain level that it can be proposed for consideration (see Annex I of the ARIA document). The recommendation follows criteria which may differ from country to country. In the USA, a guide is proposed (Table 5) which differs from that used in Europe and at the WHO (Tables 6a and 6b). The end product is a recommendation, an example of which has been given in Table 7. On the other hand, many papers proposing recommendations but without following strict stated rules cannot be used for EBM recommendation (40).

Table 5.  Levels of evidence proposed (in the USA)
lameta-analysis of randomized controlled trials (RCT)
Ibat least one RCT
IIaat least one controlled study without randomization
IIbat least one other type of study
IIInonexperimental descriptive studies
IVexpert committee reports or opinions or clinical experience of respected authorities
Table 6.  Levels of evidence: categories and strength of evidence (taken from Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. BMJ. 1999;318:593–596.)
Categories of evidence
Iameta-analysis of randomized controlled trials (RCT)
Ibat least one RCT
IIaat least one controlled study without randomization
IIbat least one other type of study
IIInonexperimental descriptive studies
IVexpert committee reports or opinions or clinical experience of respected authorities
Strength of evidence
Acategory I evidence
Bcategory II evidence or extrapolated recommendation from category I evidence
Ccategory III evidence or extrapolated recommendation from category I or II evidence
Dcategory IV evidence or extrapolated recommendation from category I, II or III evidence
Table 7.  Strength of evidence for treatment of rhinitis
 ARIA SARPAR
adultchildrenadultchildren
  1. anti-H1, antihistamine; CS, corticosteroid; SIT, specific immunotherapy.

Intervention
oral anti-H1AAAA
intranasal anti-H1AAAA
intranasal CSAAAA
intranasal cromoneAAAA
oral antileukotrieneA   
subcutaneous SITAAAA
sublingual/nasal SITAAA 
allergen avoidanceDDDD

Furthermore, guidelines should be implemented and tested for their accuracy and user-friendliness. The International Consensus on Rhinitis (41) was tested in patients with seasonal allergic rhinitis using an innovative protocol which may be the basis for further testing (Fig. 2) (42). It was found that quality-of-life and symptom reduction significantly improved in patients receiving the consensus treatment whereas in patients receiving a free-treatment option this improvement did not occur. The ARIA chronology and classification of allergic rhinitis have also been validated and the pattern of benefits for the recommendation over the free treatment is also reproduced (5). Unfortunately, there is no direct comparison with treatment strategies for asthma, one of which is used in the GINA guidelines. However, morbidity and mortality in asthma were found to be reduced in countries where guidelines are used (Fig. 3).

image

Figure 2. Treatment of seasonal allergic rhinits.

Download figure to PowerPoint

image

Figure 3. Validation of rhinitis guidelines.

Download figure to PowerPoint

Role of EBM in socio-economics

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References

Systematic reviews are also needed to inform decision-making where organization and delivery of health and social care are the objects of policy (Fig. 4). The emergence of EBM has led some clinicians to challenge managers and policy-makers to rely equally on evidence-based institutional decisions about patient care (43–45). A distinction should be made between practice policies (use of resources by practitioners), service policies (resource allocation, pattern of services), and governance policies (organizational and financial structures) (46). Evidence-based policy is being encouraged in all areas of public service, including health care (47). However, researchers should be cautious about uncritically accepting the notion of evidence-based policy (43). Currently research has little direct influence on health-service policy or governance. Researchers need a better understanding of the policy process, funding bodies must change their conception of how research influences policy, and policy-makers should become more involved in the conceptualization and conduct of research.

image

Figure 4. From EBM to health policy.

Download figure to PowerPoint

Importance of EBM in medical education of physicians and health professionals

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References

It is widely believed that the education of health professionals should be more evidence-based (48). Evidence in education should include not only formal, research-derived knowledge but also tacit knowledge (informal knowledge, practical wisdom, and shared representations of practice) (49). However, EBM is not fully implemented in postgraduate medical examinations (50).

Dissemination of EBM to patients

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References

Patients can now access evidence-based, online health information leading to a new dimension of EBM (51,52). Sources include the Cochrane Library, published by Update Software, and Clinical Evidence, published by the BMJ Publishing Group (53). In the UK, a recent poll conducted for the BMJ Publishing Group found that 88% of general practitioners surveyed said that they had patients who brought health information gathered from the Internet to the consultation (51). About 60% of general practitioners recommended that patients explore online health information sources, but less than half guided their patients to specific online sources. Moreover, involving patients in the planning and development of health care has contributed to changes in the provision of services across a range of different settings (54).

EBM and the practicing clinician

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References

The development of good guidelines does not ensure their use in practice. Systematic reviews of strategies for changing professional behaviour show that relatively passive methods of disseminating and implementing guidelines by publication in professional journals or mailing to targeted health-care professionals rarely lead to changes in professional behaviour (148). The break in continuity between clinical research and clinical practice remains intrinsic to the practice of medicine (149). Failure to recognize and account for this gap may lead to unintended and untoward consequences. Under our current understanding of EBM, the patients' individuality tends to be devalued, the focus of clinical practice is subtly shifted away from the care of individuals toward the care of populations, and the complex nature of sound clinical judgement is not fully appreciated.

EBM is forthcoming in its simplicity and few would argue against the philosophical concept. The role of EBM therefore is not to discount expert opinion (150) but, wherever possible, to base recommendations on the results of rigorous and controlled scientific study. Evidence-based recommendations often disseminate slowly – if at all – in primary care (151). Barriers to the use of EBM include the newness of the concept, the lack of relevant evidence, the difficulty of application on day-to-day practice, a negative impact on traditional medical skills and ‘the art of medicine’.

Conclusions

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References

Over the past 15 years, clinical guidelines have become an increasingly familiar part of clinical practice. Bedside clinical decisions, hospital management rules and health spending by government and insurers daily come under the direct or indirect influence of guidelines. Clinical guidelines are ‘systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances’. They may offer concise instructions on which diagnostic or screening tests to order, stipulate how medical services should be provided, how long patients should stay in hospital, or many other details relevant to clinical practice. Guidelines should be simple, adapted to the clinical setting they inform and to treatment availability in their respective geographic context and they should not be viewed as a yardstick but as support for physicians.

EBM already pervades both medical education and clinical practice. Its involvement in the development of health policies should be monitored with interest but, to use a hackneyed phrase, ‘further research is needed’. The benefits of EBM, which defines the value of medical interventions in terms of empiric evidence from clinical trials, are growing in many contexts and are well described. Not sufficiently acknowledged, however, are the limits of EBM. A gap still exists between clinical research and clinical practice which should be better recognized and assessed.

References

  1. Top of page
  2. Abstract
  3. Why do we need EBM?
  4. EBM: characteristics, advantages and drawbacks
  5. Importance of EBM in clinical recommendations
  6. Role of EBM in socio-economics
  7. Importance of EBM in medical education of physicians and health professionals
  8. Dissemination of EBM to patients
  9. Application of EBM to allergy and asthma
  10. EBM and the practicing clinician
  11. Conclusions
  12. References
  • 1
    Jackson R, Feder G. Guidelines for clinical guidelines [editorial]. BMJ, 1998;317: 427428.
  • 2
    Woolf SH, Grol R, Hutchinson A, Eccles M, Grimshaw J. Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines. BMJ, 1999;318: 527530.
  • 3
    Global strategy for asthma management andprevention. WHO/NHLBI workshop. report: National Institutes of Health, National Heart, Lung and. Blood Institute, Publication Number 95–365. Bethesda: NIH, 1995.
  • 4
    Global strategy for asthma management and prevention. http://www.ginasthma.com revised 2002.
  • 5
    Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma (ARIA) – Executive summary. Allergy, 2002;57: 841–55.
  • 6
    Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't. BMJ, 1996;312: 7172.
  • 7
    Mulrow CD, Oxman AD. Cochrane Collaboration handbook. In: Cochrane Library. Issue 4. Oxford: Update Software, 1997.
  • 8
    Culp K. Archie Cochrane. Scott Med J, 2002;47: 8990.
  • 9
    Mant D. Can randomised trials inform clinical decisions about individual patients? Lancet, 1999;353: 743746.
  • 10
    Earle CC, Weeks JC. Evidence-based medicine: a cup half full or half empty? [Editorial][in Process Citation]. Am J Med, 1999;106: 263264.
  • 11
    Couto JS. Evidence-based medicine: a Kuhnian perspective of a transvestite non- theory. J Eval Clin Pract, 1998;4: 267275.
  • 12
    Taylor DK, Buterakos J. Evidence-based medicine: not as simple as it seems. Acad Med, 1998;73: 12211222.
  • 13
    Clinicians for the Restoration of Autonomous Practice (CRAP) Writing Group. EBM: Unmasking the ugly truth. BMJ, 2002;325: 14961498.
  • 14
    Ellis J, Mulligan I, Rowe J, Sackett DL. Inpatient general medicine is evidence based. A-Team, Nuffield Department of Clinical Medicine. Lancet, 1995;346: 407410.
  • 15
    Oxman AD, Cook DJ, Guyatt GH. Users' guides to the medical literature. VI. How to use an overview. Evidence-Based Medicine Working Group. JAMA, 1994;272: 13671371.
  • 16
    Jadad AR, Cook DJ, Jones A, et al. Methodology and reports of systematic reviews and meta-analyses: a comparison of Cochrane reviews with articles published in paper-based journals. JAMA, 1998;280: 278280.
  • 17
    Barton S. Which clinical studies provide the best evidence? The best RCT still trumps the best observational study. BMJ, 2000;321: 255256.
  • 18
    Petticrew M. Why certain systematic reviews reach uncertain conclusions. BMJ, 2003;326: 756758.
  • 19
    Elstein AS, Schwarz A. Clinical problem solving and diagnostic decision making: selective review of the cognitive literature. BMJ, 2002;324: 729732.
  • 20
    Olsen O, Middleton P, Ezzo J, et al. Quality of Cochrane reviews: assessment of sample from. : BMJ, 1998;323: 829832.
  • 21
    Shea B, Moher D, Graham I, Pham B, Tugwell P. A comparison of the quality of Cochrane reviews and systematic reviews published in paper-based journals. Eval Health Prof, 2002;25: 116129.
  • 22
    Tramer MR. CONSORT, QUOROM, and structured abstracts – new rules for authors, new tools for readers. Eur J Anaesthesiol, 2001;18: 12.
  • 23
    Needleman I, Grace M, Sloan P. QUOROM and systematic reviews. Br Dent J, 2002;192: 605.
  • 24
    MacAuley D. The integration of evidence based medicine and personal care in family practice. Ir J Med Sci, 1996;165: 289291.
  • 25
    Haynes RB, Devereaux PJ, Guyatt GH. Physicians' and patients' choices in evidence based practice. BMJ, 2002;324: 1350.
  • 26
    Dearlove O, Sharples A, O'Brien K, Dunkley C. Evidence based medicine. Many questions cannot be answered by evidence based medicine. BMJ, 1995;311: 257258.
  • 27
    Maynard A. Evidence based medicine. Cost effectiveness and equity are ignored [letter;comment]. BMJ, 1996;313: 170171.
  • 28
    Hope T. Evidence based medicine and ethics [editorial]. J Med Ethics, 1995;21: 259260.
  • 29
    Gotzsche PC, Hammarquist C, Burr M. House dust mite control measures in the management of asthma: meta-analysis. BMJ, 1998;317: 11051110;discussion 1110.
  • 30
    Platts-Mills TA, Chapman MD, Wheatly LM. Control of house dust mite in managing asthma. Conclusions of meta- analysis are wrong. BMJ, 1999;318: 870871.
  • 31
    Strachan DP. House dust mite allergen avoidance in asthma. Benefits unproved but not yet excluded. BMJ, 1998;317: 10961097.
  • 32
    Gotzsche PC, Johansen HK, Burr ML, Hammarquist C. House dust mite control measures for asthma. Cochrane Database Syst Rev, 2001 ; CD001187.
  • 33
    Terreehorst I, Hak E, Oosting AJ, et al. Evaluation of impermeable covers for bedding in patients with allergic rhinitis. N Engl J Med 2003, 2001;349: 237246.
  • 34
    Woodcock A, Forster L, Matthews E, et al. Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma. N Engl J Med, 2003;349: 225236.
  • 35
    Kilburn S, Lasserson TJ, McKean M. Pet allergen control measures for allergic asthma in children and adults. Cochrane Database Syst Rev 2003 ;(1): CD002989.
  • 36
    Cuervo LG, Clarke M. Balancing benefits and harms in health care. BMJ 2003, 2003;327: 6566.
  • 37
    Ernst E, Pittler MH. Assessment of therapeutic safety in systematic reviews: literature review. BMJ, 2001;323: 546.
  • 38
    Boers M. NSAIDS and selective COX-2 inhibitors: competition between gastroprotection and cardioprotection. Lancet, 2001;357: 12221223.
  • 39
    Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. BMJ, 2002;325: 619.
  • 40
    Casale TB, Blaiss MS, Gelfand E, et al. First do no harm: managing antihistamine impairment in patients with allergic rhinitis. J Allergy Clin Immunol, 2003;111: S835S842.
  • 41
    International Rhinitis Management Working Group. International consensus report on diagnosis and management of rhinitis. Allergy, 1994;49: 134.
  • 42
    Bousquet J, Lund VJ, Van Cauwenberge P, et al. Implementation of guidelines for seasonal allergic rhinitis: a randomized controlled trial. Allergy, 2003;58: 733741.
  • 43
    Black N. Evidence based policy: proceed with care. BMJ, 2001;323: 275279.
  • 44
    Eriksson C. Learning and knowledge-production for public health: a review of approaches to evidence-based public health. Scand J Public Health, 2000;28: 298308.
  • 45
    Macintyre S. Evidence based policy making. BMJ, 2003;326: 56.
  • 46
    Webb A, Wistow G. Planning, Need and Scarcity. London: Allen & Unwin, 1986.
  • 47
    Shibuya K, Ciecierski C, Guindon E, Bettcher DW, Evans DB, Murray CJ. WHO Framework Convention on Tobacco Control: development of an evidence based global public health treaty. BMJ, 2003;327: 154157.
  • 48
    Morrison JM, Sullivan F, Murray E, Jolly B. Evidence-based education: development of an instrument to critically appraise reports of educational interventions. Med Educ, 1999;33: 890893.
  • 49
    Greenhalgh T, Toon P, Russell J, Wong G, Plumb L, Macfarlane F. Transferability of principles of evidence based medicine to improve educational quality: systematic review and case study of an online course in primary health care. BMJ, 2003;326: 142145.
  • 50
    Leung WC, Whitty P. Is evidence based medicine neglected by Royal College examinations? A descriptive study of their syllabuses. BMJ, 2000;321: 603604.
  • 51
    Ferriman A. Patients get access to evidence based, online health information. BMJ, 2002;325: 618.
  • 52
    Sigouin C, Jadad AR. Awareness of sources of peer-reviewed research evidence on the internet. JAMA, 2002;287: 28672869.
  • 53
    Nash B, Hicks C, Dillner L. Connecting doctors, patients, and the evidence. BMJ, 2003;326: 674.
  • 54
    Crawford MJ, Rutter D, Manley C, et al. Systematic review of involving patients in the planning and development of health care. BMJ, 2002;325: 1263.
  • 55
    Smith M, Iqbal S, Elliott TM, Everard M, Rowe BH. Corticosteroids for hospitalised children with acute asthma. Cochrane Database Syst Rev, 2003; ( 2 ): CD002886.
  • 56
    Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database Syst Rev 2003; ( 2 ): CD001496.
  • 57
    Walters EH, Walters J. Inhaled short acting beta2-agonist use in chronic asthma: regular versus as needed treatment. Cochrane Database Syst Rev, 2003;(2): CD001285.
  • 58
    Powell H, Gibson PG. Options for self-management education for adults with asthma. Cochrane Database Syst Rev 2003; ( 1 ):CD004107
  • 59
    Gibson PG, Powell H, Coughlan J, et al. Self-management education and regular practitioner review for adults with asthma. Cochrane Database Syst Rev 2003; ( 1 ):CD001117.
  • 60
    Wolf FM, Guevara JP, Grum CM, Clark NM, Cates CJ. Educational interventions for asthma in children. Cochrane Database Syst Rev 2003; ( 1 ):CD000326.
  • 61
    Walters EH, Walters JA, Gibson PW. Regular treatment with long acting beta agonists versus daily regular treatment with short acting beta agonists in adults and children with stable asthma. Cochrane Database Syst Rev 2002; ( 4 ):CD003901.
  • 62
    Dewey A, Bara A, Dean T, Walters H. Dapsone as an oral corticosteroid sparing agent for asthma. Cochrane Database Syst Rev 2002; ( 4 ):CD003268.
  • 63
    Hondras MA, Linde K, Jones AP. Manual therapy for asthma. Cochrane Database Syst Rev 2002; ( 4 ):CD001002.
  • 64
    Toelle BG, Ram FS. Written individualised management plans for asthma in children and adults. Cochrane Database Syst Rev 2002; ( 3 ):CD002171.
  • 65
    Woods RK, Thien FC, Abramson MJ. Dietary marine fatty acids (fish oil) for asthma in adults and children. Cochrane Database Syst Rev 2002; ( 3 ):CD001283.
  • 66
    Singh M, Bara A, Gibson P. Humidity control for chronic asthma. Cochrane Database Syst Rev 2002; ( 2 ): CD003563.
  • 67
    Gibson PG, Powell H, Coughlan J, et al. Limited (information only) patient education programs for adults with asthma. Cochrane Database Syst Rev 2002; ( 2 ): CD001005.
  • 68
    Cates CJ, Rowe BH, Bara A. Holding chambers versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev 2002; ( 2 ): CD000052.
  • 69
    Jones A, Fay JK, Burr M, Stone M, Hood K, Roberts G. Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2002; ( 1 ): CD003537.
  • 70
    Fay JK, Jones A, Ram FS. Primary care based clinics for asthma. Cochrane Database Syst Rev 2002; ( 1 ): CD003533.
  • 71
    Adams NP, Bestall JB, Jones PW. Inhaled beclomethasone versus placebo for chronic asthma. Cochrane Database Syst Rev 2000; ( 4 ): CD002738.
  • 72
    Adams N, Bestall JM, Jones PW. Inhaled beclomethasone versus budesonide for chronic asthma. Cochrane Database Syst Rev 2002; ( 1 ): CD003530.
  • 73
    Adams N, Bestall JM, Jones PW. Inhaled fluticasone at different doses for chronic asthma. Cochrane Database Syst Rev 2002; ( 1 ): CD003534.
  • 74
    Adams N, Bestall JM, Jones PW. Fluticasone versus beclomethasone or budesonide for chronic asthma. Cochrane Database Syst Rev 2002; ( 1 ): CD002310.
  • 75
    Adams N, Bestall J, Jones PW. Inhaled fluticasone proprionate for chronic asthma. Cochrane Database Syst Rev 2001; ( 3 ): CD003135.
  • 76
    Adams N, Bestall J, Jones PW. Budesonide at different doses for chronic asthma. Cochrane Database Syst Rev 2001; ( 4 ): CD003271.
  • 77
    Adams N, Bestall J, Jones PW. Budesonide for chronic asthma in children and adults. Cochrane Database Syst Rev 2001; ( 4 ): CD003274.
  • 78
    Adams N, Bestall J, Jones P. Inhaled beclomethasone at different doses for long-term asthma. Cochrane Database Syst Rev 2001; ( 1 ): CD002879.
  • 79
    Sheikh A, Alves B, Dhami S. Pneumococcal vaccine for asthma. Cochrane Database Syst Rev 2002; ( 1 ): CD002165.
  • 80
    Ram FS, Brocklebank DM, White J, Wright JP, Jones PW. Pressurised metered dose inhalers versus all other hand-held inhaler devices to deliver beta-2 agonist bronchodilators for non-acute asthma. Cochrane Database Syst Rev 2002; ( 1 ): CD002158.
  • 81
    Jones A, Rowe B, Peters J, Camargo C, Hammarquist C. Inhaled beta-agonists for asthma in mechanically ventilated patients. Cochrane Database Syst Rev 2001; ( 4 ): CD001493.
  • 82
    Mitra A, Bassler D, Ducharme FM. Intravenous aminophylline for acute severe asthma in children over 2 years using inhaled bronchodilators. Cochrane Database Syst Rev 2001; ( 4 ): CD001276.
  • 83
    Bara AI, Barley EA. Caffeine for asthma. Cochrane Database Syst Rev 2001; ( 4 ): CD001112.
  • 84
    Wark P, Wilson AW, Gibson PG. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev 2001; ( 4 ): CD001108.
  • 85
    Kaur B, Rowe BH, Ram FS. Vitamin C supplementation for asthma. Cochrane Database Syst Rev 2001; ( 4 ): CD000993.
  • 86
    Ardern KD, Ram FS. Tartrazine exclusion for allergic asthma. Cochrane Database Syst Rev 2001; ( 4 ): CD000460.
  • 87
    Ardern KD, Ram FS. Dietary salt reduction or exclusion for allergic asthma. Cochrane Database Syst Rev 2001; ( 4 ): CD000436.
  • 88
    Sheikh A, Alves B, Dhami S. Pneumococcal vaccine for asthma. Cochrane Database Syst Rev 2001; ( 3 ): CD002165.
  • 89
    Evans DJ, Cullinan P, Geddes DM. Cyclosporin as an oral corticosteroid sparing agent in stable asthma. Cochrane Database Syst Rev 2001; ( 2 ): CD002993.
  • 90
    Travers A, Jones AP, Kelly K, Barker SJ, Camargo CA, Rowe BH. Intravenous beta2-agonists for acute asthma in the emergency department. Cochrane Database Syst Rev 2001; ( 2 ): CD002988.
  • 91
    Evans DJ, Cullinan P, Geddes DM. Troleandomycin as an oral corticosteroid steroid sparing agent in stable asthma. Cochrane Database Syst Rev 2001; ( 2 ): CD002987.
  • 92
    Evans DJ, Cullinan P, Geddes DM. Gold as an oral corticosteroid sparing agent in stable asthma. Cochrane Database Syst Rev 2001; ( 2 ): CD002985.
  • 93
    Beamon S, Falkenbach A, Fainburg G, Linde K. Speleotherapy for asthma. Cochrane Database Syst Rev 2001; ( 2 ): CD001741.
  • 94
    Cates CJ, Rowe BH. Holding chambers versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD000052.
  • 95
    Cates CJ, Jefferson TO, Bara AI, Rowe BH. Vaccines for preventing influenza in people with asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD000364.
  • 96
    Cates CJ, Jefferson TO, Bara AI, Rowe BH. Vaccines for preventing influenza in people with asthma (Cochrane Review). Cochrane Database Syst Rev 2000; ( 4 ): CD000364.
  • 97
    Cates CJ, Adams N, Bestall J. Holding chambers versus nebulisers for inhaled steroids in chronic asthma. Cochrane Database Syst Rev 2001; ( 2 ): CD001491.
  • 98
    Cates C. Spacers and nebulisers for the delivery of beta-agonists in non-life-threatening acute asthma. Respir Med 2003, 2003;97: 762769.
  • 99
    Cates C. Overlooking of Cochrane reviews in asthma research. Lancet, 2000;355: 70.
  • 100
    Rodrigo G, Rodrigo C, Pollack C, Travers A. Helium-oxygen mixture for nonintubated acute asthma patients. Cochrane Database Syst Rev 2001 ; ( 1 ): CD002884.Cochrane Database Syst Rev. (1): CD002884.
  • 101
    Edmonds ML, Camargo CA, Pollack CV, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev 2001; ( 1 ): CD002308.
  • 102
    Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev 2001; ( 1 ): CD002178.
  • 103
    Mash B, Bheekie A, Jones PW. Inhaled vs oral steroids for adults with chronic asthma. Cochrane Database Syst Rev 2001; ( 1 ): CD002160.
  • 104
    Manser R, Reid D, Abramson M. Corticosteroids for acute severe asthma in hospitalised patients. Cochrane Database Syst Rev 2001; ( 1 ): CD001740.
  • 105
    Haby MM, Waters E, Robertson CF, Gibson PG, Ducharme FM. Interventions for educating children who have attended the emergency room for asthma. Cochrane Database Syst Rev 2001; ( 1 ): CD001290.
  • 106
    Hondras MA, Linde K, Jones AP. Manual therapy for asthma. Cochrane Database Syst Rev 2001; ( 1 ): CD001002.
  • 107
    Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev 2001; ( 1 ): CD000195.
  • 108
    Parameswaran K, Belda J, Rowe BH. Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma. Cochrane Database Syst Rev 2000; ( 4 ): CD002742.
  • 109
    Kelly K, Spooner CH, Rowe BH. Nedocromil sodium vs. sodium cromoglycate for preventing exercise-induced bronchoconstriction in asthmatics. Cochrane Database Syst Rev 2000; ( 4 ): CD002731.
  • 110
    Campbell F, Jones K. Feather vs. non-feather bedding for asthma. Cochrane Database Syst Rev 2000; ( 4 ): CD002154.
  • 111
    Walters EH, Walters J. Inhaled short acting beta2-agonist use in asthma: regular vs as needed treatment. Cochrane Database Syst Rev 2000; ( 4 ): CD001285.
  • 112
    Woods RK, Thien FC, Abramson MJ. Dietary marine fatty acids (fish oil) for asthma. Cochrane Database Syst Rev 2000; ( 4 ): CD001283.
  • 113
    Edmonds ML, Camargo CA, Saunders LD, Brenner BE, Rowe BH. Inhaled steroids in acute asthma following emergency department discharge. Cochrane Database Syst Rev 2000; ( 3 ): CD002316.
  • 114
    Edmonds ML, Camargo CA, Pollack CV, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev 2000; ( 3 ): CD002308.
  • 115
    Holloway E, Ram FS. Breathing exercises for asthma. Cochrane Database Syst Rev 2000; ( 3 ): CD001277.
  • 116
    Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev 2000; ( 2 ): CD002178.
  • 117
    Mash B, Bheekie A, Jones PW. Inhaled vs oral steroids for adults with chronic asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD002160.
  • 118
    Manser R, Reid D, Abramson M. Corticosteroids for acute severe asthma in hospitalised patients. Cochrane Database Syst Rev 2000; ( 2 ): CD001740.
  • 119
    Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database Syst Rev 2000; ( 2 ): CD001496.
  • 120
    Jones A, Rowe B, Peters J, Camargo C, Hammarquist C. Inhaled beta-agonists for asthma in mechanically ventilated patients. Cochrane Database Syst Rev 2000; ( 2 ): CD001493.
  • 121
    Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo CA Jr. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev 2000; ( 2 ): CD001490.
  • 122
    Sharek PJ, Bergman DA. Beclomethasone for asthma in children: effects on linear growth. Cochrane Database Syst Rev 2000; ( 2 ): CD001282.
  • 123
    Wilson AJ, Gibson PG, Coughlan J. Long acting beta-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD001281.
  • 124
    Hammarquist C, Burr ML, Gotzsche PC. House dust mite control measures for asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD001187.
  • 125
    Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD001186.
  • 126
    Gibson PG, Coughlan J, Wilson AJ et al. Self-management education and regular practitioner review for adults with asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD001117.
  • 127
    Ram FS, Robinson SM, Black PN. Physical training for asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD001116.
  • 128
    Gibson PG, Coughlan J, Wilson AJ et al. Limited (information only) patient education programs for adults with asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD001005.
  • 129
    Hondras MA, Linde K, Jones AP. Manual therapy for asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD001002.
  • 130
    Dennis J. Alexander technique for chronic asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD000995.
  • 131
    Davies H, Olson L, Gibson P. Methotrexate as a steroid sparing agent for asthma in adults. Cochrane Database Syst Rev 2000; ( 2 ): CD000391.
  • 132
    Linde K, Jobst KA. Homeopathy for chronic asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD000353.
  • 133
    Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD000195.
  • 134
    Panton J, Barley EA. Family therapy for asthma in children. Cochrane Database Syst Rev 2000; ( 2 ): CD000089.
  • 135
    Linde K, Jobst K, Panton J. Acupuncture for chronic asthma. Cochrane Database Syst Rev 2000; ( 2 ): CD000008.
  • 136
    Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 1998, 2001;317: 16241629.
  • 137
    Wilson DR, Torres LI, Durham SR. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev 2003 ; ( 2 ): CD002893.
  • 138
    Sheikh A, Hurwitz B. House dust mite avoidance measures for perennial allergic rhinitis. Cochrane Database Syst Rev 2001; ( 4 ): CD001563.
  • 139
    Dean T. The Cochrane Collaboration and its contribution towards the management of allergic diseases. Clin Exp Allergy 2002, 2003;32: 12691273.
  • 140
    Kramer MS. Maternal antigen avoidance during pregnancy for preventing atopic disease in infants of women at high risk. Cochrane Database Syst Rev 2000 ; ( 2 ): CD000133.
  • 141
    Kramer MS. Maternal antigen avoidance during lactation for preventing atopic disease in infants of women at high risk. Cochrane Database Syst Rev 2000; ( 2 ): CD000132.
  • 142
    Kramer MS. Maternal antigen avoidance during lactation for preventing atopic eczema in infants. Cochrane Database Syst Rev 2000; ( 2 ): CD000131.
  • 143
    Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev 2002; ( 1 ): CD003517.
  • 144
    Ram FS, Ducharme FM, Scarlett J. Cow's milk protein avoidance and development of childhood wheeze in children with a family history of atopy. Cochrane Database Syst Rev 2002; ( 3 ): CD003795.
  • 145
    Seidman EG, Singer S. Therapeutic modalities for cow's milk allergy. Ann Allergy Asthma Immunol 2003, 2000;90: 104111.
  • 146
    Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess, 2000;4: 1191.
  • 147
    Klein PA, Clark RA. An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol, 1999;135: 15221525.
  • 148
    Feder G, Eccles M, Grol R, Griffiths C, Grimshaw J. Clinical guidelines: using clinical guidelines. BMJ, 1999;318: 728730.
  • 149
    Tonelli MR. The philosophical limits of evidence-based medicine. Acad Med, 1998;73: 12341240.
  • 150
    Hayward RS, Wilson MC, Tunis SR, Bass EB, Guyatt G. Users' guides to the medical literature. VIII. How to use clinical practice guidelines. A. Are the recommendations valid? The Evidence-Based Med Working Group. JAMA, 1995;274: 570574.
  • 151
    Berwick DM. Disseminating innovations in health care. JAMA, 2003;289: 19691975.
  • 152
    Sackett DL, Rosenberg WM. The need for evidence-based medicine. J R Soc Med., 1995;88: 620624.
  • 153
    Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. BMJ, 1999;318: 593596.