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r ctice uidelines

n linic I rials
joseph M. Swanson, PharmD, BCPS

The volume of medically related research published
each year is staggering. Searching a medical citation
database will often produce in excess of 7 50,000 publications in one year's time. Unfortunately, the vast
amount of information produced presents a significant
dilemma for clinicians trying to stay up to date in their
practice. It is impractical-and likely impossible-for
any single clinician to review and process all of the
available literature pertaining to his or her practice.
Thus, a mechanism to inform clinicians about important information related to their clinical practice is
imperative.
Interestingly, despite the numerous publications
produced yearly, a significant number of unanswered
questions still exist for important clinical scenarios.
This dilemma may be even more difficult for the
practicing clinician, because he or she has nowhere
to turn to determine the appropriate action in such
cases. This situation is referred to as the art of
medicine. Unfortunately, patients are at risk of receiving less than optimal care in these situations.
Again, it is extremely important for clinicians to be
able to seek guidance for these troubling clinical
situations.
Even when the clinician is knowledgeable about
current literature supporting specific care, patients
often do not receive optimal care. Translating evidence produced in the medical literature into clinical
practice poses many problems, especially when new
data are generated that may alter the best approach to
a specific clinical condition. Additionally, conflicting
results often produce two or more schools of thought
as to the best practice despite adequate evidence of
any specific action.
Clinical practice guidelines incorporate the vast
evidence for a specific topic and present it in a con-

cise, organized, and easily understandable fashion.
Because clinical practice guidelines evaluate the available literature and provide clinicians with a system for
understanding the strength of this evidence, they are
often referred to as evidence-based guidelines.

27·1 Principles of Clinical
Practice Guidelines for
Various Diseases and
Their Interpretation in
the Clinical Setting
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literature Categories

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When posed with a clinical dilemma, the clinician can
turn to colleagues for assistance, or he or she can
research the question using various types of literature. The literature available to the clinician ranges
widely. Any published literature may be incorporated into practice as long as the strengths and limitations of each are understood and addressed. Following
are various types of studies published in the medical
literature:
Randomized controlled trials, which are considered the most statistically rigorous
ra N onrandomized trials
c! Observational studies
o Cohort studies
o Case control studies
(• Cross-sectional studies
The ability to apply individual studies directly to patient care can be impaired because of study limitations.

EBM highlights the quality of literature used to support the intervention. More information on the Cochrane Collaboration is available at www.The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination® Therefore. Additionally. Each is integral when applying evidence from clinical trials to an individual patient with a specific medical condition. Traditional clinical practice guidelines require the reader to trust that the expert guideline developers have sufficiently evaluated the available literature. Guidelines seek to provide evidence-based information to the practicing clinician regarding various aspects of a disease state or clinical condition. tables. These variations are unrelated to a patient's severity of illness but are often associated with other factors. and are developed by leading clinicians in the field. The term decision analysis was introduced in the 1970s. The I addresses the clinical intervention. The 0 is for the desired clinical outcome that is used to compare interventions. A more detailed description is provided later in this chapter. Using the mnemonic provides a semiformal structure that can be applied to any clinical problem. and best practice guides. and specific clinical situations. it does not allow for immediate application of information to a specific patient problem. The purpose is to provide recommendations for clinicians.cochrane. conducting a systematic literature review is impractical for the individual clinician. Unfortunately. one must discuss the foundation on which they are built.org. When using PICO. generally in the form of decision trees." and their purpose is "to make explicit recommendations with a definite intent to influence what clinicians do" (Field and Lohr 1992). The P refers to the patient's problem. EBM forms the basis for the current approach to patient care. provide recommendations specifically to guide patient care. In the 1950s. The meta-analyses available through the Cochrane Collaboration provide important information to clinicians seeking answers to a very specific question. Clinical practice guidelines emulate the goals of the Cochrane Collaboration. Additionally. Thus. It was suggested that incorporation of statistics and probabilities could improve medical decision making. Development of the Cochrane Collaboration was an effort to provide regularly updated reviews of clinically important questions. Definition of Evidence~Based Medicine To understand clinical practice guidelines. Essentially two types of clinical practice guidelines exist. flowcharts. The reviews are intended for a broad readership that does not have time for an individual. EBM approaches a clinical dilemma as an answerable clinical question represented by the mnemonic PICO. clinical practice guidelines are "systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. patients. the traditional form and the evidencebased form. the first argument for a methodological approach to medical decision making was presented. varying portions of the guidelines are determined by expert opinion or perceived best practices. the medical community has embraced EBM more than MDM. scientists use other methods to investigate the results identified in individual studies: ~ !k'l Meta-analysis Review Systematic review Clinical practice guidelines Clinical practice guidelines are generally broader than the preceding types of literature. and critical review of the literature. These statements incorporate key factors such as a systematic review of the literature. the reader must . it supports a systematic literature review or meta-analysis when conflicting evidence exists. Both address the concern for variations in clinical practice resulting in less than optimal care of patients. they do not always include a comprehensive review and often do not provide ratings for the strength of recommendations. Thus. such as geography or socioeconomic status. Although these guidelines usually incorporate primary literature into the process. Performing a meta-analysis is extremely time consuming and is likely not feasible for the practicing clinician. Definition of Clinical Practice Guidelines According to the Institute of Medicine. evidenced-based medicine (EBM) and medical decision making (MDM) became more prominent in the medical community. The C represents a comparison of the intervention with at least one alternative. and it emphasizes different levels of significance based on the research methods employed in the published study. Although a review can be done over a period of time. Experts in a specific field develop the traditional clinical practice guidelines. In the 1980s. careful. Although EBM and MDM have common foundations. clinicians. but on a broader scale.

Both types of guidelines may provide insight into important aspects of a clinical condition that the cur- rently published literature does not adequately address. They then apply a grade for the recommendation that is based on the strength of available literature. They are still developed by an expert panel. The detailed text focuses on the evidence provided by important primary literature.) Patient response Yes Continue therapy and monitor Source: Author's representation. not only randomized clinical trials but also less rigorous study designs such as retrospective reviews. A table usually provides the definitions for the grading of recommendations and supporting evidence. That section is generally titled "Future Research" and is used to stimulate researchers to attempt to answer the important questions included there. Figure 27-1 provides 'at~l:l27~1. case studies. Anatomy of a Clinical Practice Guideline The anatomy of a clinical practice guideline is fairly simple. This review includes all literature on a specific topic. No l Alternative therapy . creating a customized pathway. methodological review of the literature. Evidence-based guidelines identify the literature supporting specific recommendations. etc. because that is not always evident in the published document. and if so. tests. which is followed by a more detailed text describing the supporting evidence for the recommendation. a major difference is a comprehensive. A guideline generally contains text introducing the guideline. The use of less-than-optimal literature leads to the next important aspect of evidence-based guidelines. These types of guidelines can include expert opinions. The general nature of these pathways is intended to provide a starting point for clinicians to incorporate regional or local practice variations into guideline recommendations.Practice Guidelines and Clinical Trials have faith that the guideline development was free of bias. many guidelines provide an abbreviated text of the recommendation. However. this inclusion is clear in the recommendation. and prospective nonrandomized studies. Evidence-based clinical practice guidelines take a more systematic approach than do traditional guidelines. medications. Generic Example of a Clinical Pathway • Clinical conditions that would qualify the individual patient for entrance into the treatment pathway Yes I No Patient is out of pathway or requires periodic reevaluation Actions to take (procedures. Guidelines often provide suggested clinical pathways for diagnosis and treatment of the clinical condition. evaluation of the strength of supporting literature. Following those sections.

but not all. etc. it should highlight recently identified information. Although variations exist. and methodology used in the development. All guidelines provide a references section that allows clinicians to find original studies supporting recommendations in the guidelines. This information should have some relevance to the clinical condition and therapies that address the newly identified pathogenesis. Those sections provide the transparency considered so important when evaluating the integrity of a guideline. Some. This section is one of the most important for pharmacists. The quality of evidence supporting recommendations is described by grading systems.) without flaws Very low 4 D Noncontrolled studies with flaws or expert opinions Source: Author's compilation. depending on the expert panel developing the guidelines. Some guidelines will contain sections that describe how to monitor for response to therapy. Guidelines begin with a formal explanation of the intent. separate guidelines may focus entirely on this aspect of the condition. Outline of a Clinical Practice Guideline Summary of the intent and scope of the clinical practice guideline Methodology used to develop and prepare the guideline Grading system for ranking recommendations in the guideline Introduction to the topic Epidemiology of the clinical condition Pathogenesis of the clinical condition Prevention of the clinical condition (if possible) Diagnosis and evaluation of the clinical condition Therapy for the clinical condition Evaluation of response to therapy Identification of important clinical questions not addressed in the literature Suggestions for future research on the clinical condition may contain as much information as the diagnosis section. These sections can be important to pharmacists because they can contain recommendations for determining medication failure. Diagnosis and evaluation of the clinical condition is one of the most important areas of a guideline and likely contains the majority of recommendations. . Most clinicians are relatively aware of this information. guidelines include sections identifying important clinical questions not yet answered and areas for future research. Example of an Evidence Grading System Quality of supporting evidence Numbers High letters Types of studies A Randomized controlled trials without limitations Moderate 2 B Randomized controlled trials with limitations or nonrandomized controlled trials (cohort. changing the medication therapy. case reports. case-control studies. Grading systems are presented in different variations of letters and numbers. scope. A section describing the prevention of the condition may or may not be relevant. The quality of evidence generally ranges from high to ·1. An introduction highlights the condition and the reasons it is important to clinicians. most grading tends to follow similar formats to that in Table 27-1. If pathogenesis is included in a guideline. clinical practice guidelines provide clinicians guidance for recommendations.!J~~~ 27·1. Source: Author's compilation. Following that section is a brief epidemiology of the condition. These sections usually guide researchers toward areas of important concern or possible breakthroughs in patient care.) without limitations Low 3 c Nonrandomized controlled trials with limitations or noncontrolled studies (observational studies.The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination® a generic example. In conditions where prevention is feasible. case series. Additionally. Therapy for the condition is the only section that 1?. because it usually contains the relevant literature for medications. levels of Evidence As previously mentioned. The references also allow clinicians the opportunity to incorporate inclusion and exclusion criteria of specific studies in local practice. etc. T abies are used to highlight important facts that all clinicians should remember. The general outline of a clinical practice guideline should be included at the beginning of the document. or identifying medication-related adverse effects. such sections alert clinicians to future literature that may change practice. if this information was not included in the introduction. but guidelines can provide the most recent information. Some conditions are preventable. Box 27-1 provides a sample outline of a clinical practice guideline.

and grading the supporting literature. The use of two different scales provides an easily understandable and concise form of grading. moderate. Development. The strength of a recommendation generally correlates with the strength of the supporting evidence. all guidelines could provide the same grading regardless of the expert panel developing the guideline. As previously mentioned. For example. Some are published online. Until this occurs. However. Some guidelines will simplify the grading level to high. and . Current clinical guidelines have no standardized method of grading the literature and recommendation. clinicians are expected to review each guideline carefully and determine how the recommendations and supporting eyidence are graded. Table 27-2 provides an example of a grading system for guideline recommendations. logical approach to grading the quality of evidence and the strength of recommendations. Although the combination of numbers and letters can effectively communicate the strength of the recommendation." usually with a negative risk-versus-benefit ratio. a guideline will have recommendations for clinically important conditions. Finally. These strengths are often represented by letters or numbers. However. not all practice guidelines appear in indexed journals. Unfortunately. a complete review of the literature is impractical. no direct evidence supports this effect. Evidence-based guidelines not only grade the level of supporting evidence. and low. the strength of the recommendation · usually provides a risk-versus-benefit determination. The GRADE (Grading of Recommendations Assessment. Interestingly. a strong recommendation with strong supporting evidence would likely be graded as a 1A recommendation. The belief is that restricting the number of levels in a grading system makes the system easier for the clinician to understand.Practice Guidelines and Clinical Trials very low. Example of a Recommendation Grading System Recommendation strength Numbers Recommend implementing letters A Risk vs. The higher level of evidence usually correlates to a lower number or a letter appearing sooner in the alphabet. This lack of standardization makes it extremely important that the reader of the guideline first determine what grading scale is used in a specific clinical practice guideline. A search of MEDLINE may produce the appropriate guideline as long as it is published in an indexed journal. This outcome would allow clinicians to compare and contrast grading of recommendations across the board. to "recommend not implementing the recommendation. as with the grading of evidence. but also usually grade the strength of the recommendation. no research addresses the most effective method of grading either the recommendation or the supporting evidence. where does this clinician go to find the appropriate guidelines? Many would immediately turn to a bibliographic database such as the National Library of Medicine's MEDLINE. One of the most efficient methods is to identify a clinical practice guideline that addresses the patient's specific condition. If this working group is successful. However. and Evaluation) Working Group was formed with the idea of reaching an agreement on a uniform. The symbols used for the recommendation strength are usually different from those used for grading of evidence. Finding Applicable Guidelines If a clinician wishes to apply EBM to one of his or her patients. the clinician needs to sort out the differences in grading levels and supporting evidence produced in different guidelines. as indicated by the corresponding letter or number. Many times the same number or letter has a different meaning depending on the organization or expert panel. A combination of letters and symbols is often used when providing strength for the recommendation 27=2. benefit Desirable effects with benefit clearly outweighing risk Consider implementing 2 B Desirable effects with benefit appearing to outweigh risk Consider not implementing 3 c Possible undesirable effects with risk appearing to outweigh benefit Recommend not implementing 4 D Undesirable effects with risk clearly outweighing benefits Source: Author's compilation." usually corresponding to a positive risk-versus-benefit ratio. Evidence-based guidelines provide an explanation of the grading system and study designs associated with each level. Recommendation strength can range from "recommend implementing the recommendation. lack of uniformity may cause confusion. It is anticipated that standardized grading could improve compliance by clinicians.

Department of Health and Human Services. Additionally. Infectious Diseases Society of America. Guidelines are generally pub- Sources for Obtaining Clinical Practice Guidelines Agency for Healthcare Research and Quality.nlm. especially when more than one set of guidelines exists for a specific clinical con- '\"'1e 27·3.gov Medical Matrix. The site contains 3. A search of this database might miss important. it is frequently used to obtain fulltext clinical practice guidelines for multiple clinical conditions. American College of Chest Physicians. clinically relevant guidelines. In fact. MEDLINE does notalways provide access to the full text of cited guidelines. Some Commonly Used Clinical Practice Guidelines Guideline Supporting organization Antithrombotic and Thrombolytic Therapy American College of Chest Physicians Reports of the Joint National Committee on Prevention. www.cdc. the Infectious Diseases Society of America. he or she might not be able to access the entire text and thus not be able to evaluate recommendations in the guideline.guideline.org National Library of Medicine. Japanese Association for Acute Medicine. www. www. National Institutes of Health. Evaluation of Clinical Practice Guidelines The evaluation of clinical practice guidelines is important when determining whether to apply recommendations directly to patients. and Society of Infectious Diseases Pharmacists Source: Author's compilation. and World Federation of Societies of Intensive and Critical Care Medicine Therapeutic Monitoring of Vancomycin in Adult Patients: A Consensus Review of the American Society of HealthSystem Pharmacists. Lung. lished in well-respected peer-reviewed journals. Society of Hospital Medicine. Lung. International Sepsis Forum. American College of Emergency Physicians.The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination® others may appear in nonindexed journals. Detection. and Blood Institute Guidelines tor the Diagnosis and Management of Asthma U. Examples of commonly referenced clinical practice guidelines are included in Table 27-3. Evaluation.S. Fortunately. and National Heart. more than one organization often supports the guideline. National Guideline Clearinghouse. the Internet offers several choices to access a variety of guidelines.ncbi.medmatrix. European Society of Clinical Microbiology and Infectious Diseases. and availability ranges from easily accessible online copies to required journal subscription hard copies. Japanese Society of Intensive Care Medicine. Society of Critical Care Medicine.nih. European Society of Intensive Care Medicine. . and the Society of Infectious Diseases Pharmacists American Society of Health-System Pharmacists. and Treatment of High Blood Pressure National Heart. The National Guideline Clearinghouse is an initiative of the Agency for Healthcare Research and Quality and U.fcgi? rid=hstat Source: Author's compilation. Surgical Infection Society. As indicated in the table. Canadian Critical Care Society. Department of Health and Human Services. Health Servicesrrechnology Assessment Text.S. It is a public resource for evidence-based clinical practice guidelines. the clinician has other options. European Respiratory Society. The Web sites listed in Box 2 7-2 provide access to various guidelines.gov/books/bv.gov Centers for Disease Control and Prevention.060 guidelines from 289 organizations worldwide. Even if the clinician were to find the appropriate guideline. www. and Blood Institute ACCF!AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults American College of Cardiology Foundation and American Heart Association ADA Clinical Practice Recommendations American Diabetes Association Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock American Association of Critical-Care Nurses.

- ' / The two main reasons for directly applying to patients the evidence-based recommendations from clinical practice guidelines are as follows: ft.. r'lll rmJ Applicability. This section addresses the key factors in implementing the guideline. Editorial independence. and the target patient population. only the number 1 (strongly disagree) is used. It evaluates the independence and possible conflicts of interest of the development group. This section focuses on the language used in the guideline and how the authors have formatted the document. other reports suggest that Americans do not receive care based on the best available scientific evidence. times the number of appraisers. it determines the methods used to produce recommendations. This section determines the degree to which the guideline represents the views of clinicians using the guideline and the target patient population. Clarity and presentation. All items within a section are scored.Practice Guidelines and Clinical Trials clition. Additionally. In 2000. In doing so. Both guidelines address prevention of deep vein thrombosis in traumatically injured patients. 27·2. Table 27-4 shows a sample score. stating that up to 98. For example. This section investigates the degree to which the development group researched the available evidence. It addresses the processes used to gather.. and the total score is tallied for each user review. The standardized score accounts for all users' input and the maximum and minimum scores possible. and evaluate the available literature. The Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument. Rigor of development. provides a tool for guideline users to assess the methodological quality of clinical practice guidelines. Incorporating clinical practice guidelines into local practice assists clinicians in identifying the best care. To Err Is Human. Based Knowledge into Treatment Protocols and Clinical Practice Guidelines "'"'"'~'"'"'""''''''"""''''"''!.agreecollaboration. Each section addresses a different aspect of a guideline's quality. Stakeholder involvement. Then the clinician must determine which recommendations to incorporate in the care of his or her patients.\ Improving patient care. including organizational. This section deals mostly with the developers of the guideline. but the recommendations of each differ slightly.000 inpatients die unnecessarily. the Institute of Medicine published a report. These deaths can be attributed to medical error. a study demonstrated that applying the community-acquired pneumonia guidelines to patients reduced their length of stay and mortality in the hospital. patient outcomes are improved. clinicians caring for trauma patients are responsible for reviewing each set of guidelines and the literature supporting recommendations for each. Additionally. Integration of Scientific and Systems. synthesize..org/instrument. This rate is unacceptable and has spurred attempts to improve patient care. !Ill ~~ ~ illl Scope and purpose. The authors of the AGREE Instrument state that it is intended for use by the following groups: Policy makers-to decide which guidelines can be recommended for use in practice m Guideline developers-to follow a structured and rigorous development methodology and to use a self-assessment tool to ensure that their guidelines are sound ulll Health care providers-to undertake their own assessment before adopting the recommendations Educators or teachers-to help enhance critical appraisal skills among health professionals The AGREE Instrument consists of 23 items that are organized in six different sections. It focuses on the overall purpose of the guideline. Each item may receive a minimum score of 1 (indicating the user strongly disagrees with the item statement) and a maximum score of 4 (indicating the user strongly agrees with the item statement).-. the important clinical questions addressed. The 23 items in the six sections are organized so that the user of the instrument can rank his or her evaluation of the guideline. This section deals with the major aspects of the guideline. and cost implications. The total score for each user is added together to determine the obtained score. which is available at www . A prime example is the CHEST (American College of Chest Physicians) guidelines for the prevention of venous thromboembolism and the EAST (Eastern Association for the Surgery of Trauma) guidelines for management of venous thromboembolism. behavioral. The minimum score is calculated in the same way as the maximum. Therefore.'JC-. The maximum score is the number 4 (strongly agree) times the number of items in a section. .

If clinicians follow guidelines. patient charges were reduced. pathways. pathways. as illustrated in Figure 27-2. If patients receive better care.. Many clinicians are concerned that protocols remove clinical decision making. They may be used independently but are often combined with protocols. Although clinicians view each of these methods differently. tB The general process of incorporating newly identified clinical evidence or clinical practice guidelines into direct patient care has several steps. pathways provide a plan for a course of action but generally allow the clinician to make decisions.8% Maximum score. patient care may be completely determined by the protocol. In contrast. It tends to be the most restrictive form of dictating care. Common forms of incorporating clinical practice guidelines into patient care include protocols. Guidelines. Pharmacists should be involved in each step of this process. thus removing the clinician from the care of patients. tm Order sets. they leave the decisions completely to the clinician. the role for the pharmacist in integration of new evidence into direct patient care is most prominent in the later steps in the process. they can be categorized by how much they restrict clinician decision making: Protocols. and order sets. They provide the most autonomy for clinicians. they will be less likely to miss important clinical issues. or guidelines. By providing options for clinicians. Step 2: Dissemination. Identifying clinical issues sooner permits reduction in medical costs or avoidance of those costs altogether. Depending on the protocol. However. A protocol is a plan for a course of medical care of patients. they will be more likely to address health concerns sooner. Applying clinical practice guidelines to patient care not only improves patient outcomes but also can reduce costs. Medical researchers generate new evidence and report the results of specific studies in medical journals.Minimum score 51. Pathways. but pharmacists can be integral in this step. Pharmacists can conduct journal club meetings to highlight important evidence that should .Minimum score Example: 23-9 36-9 Source: Based on AGREE Collaboration 2009. The American Society of Health-System Pharmacists developed guidelines addressing the pharmacist's role in this process: ''~1 Step 1: New evidence. They are often considered less restrictive than protocols.le 27·4. All health care practitioners are responsible for disseminating newfound knowledge. guidelines. Pharmacists are playing a bigger role in the generation of new evidence now than ever before.The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination® ". Lowering cost. Although guidelines provide evidence. In the community-acquired pneumonia example. order sets aim to clue the user into thinking about specific aspects of care. Example of AGREE Instrument Scoring Total Item 1 Item 2 Item 3 User 1 2 2 3 7 User 2 3 3 3 9 User 3 3 2 7 Total 8 7 2 8 Maximum score (Strongly agree) x (number of users) x (number of items) 23 36 Example: 4 x 3 x 3 Minimum score (Strongly disagree) x (number of users) x (number of items) 9 Example: 1 x 3 x 3 Standardized score Obtained score.

one must bring local practice leaders together to determine the best method of applying the new evidence to patient care. Process by Which New Research Is Incorporated into Clinical Practice Step 1: New evidence Step 7: Assessment Step 2: Dissemination Step 6: Implementation Step 3: Acceptance Step 5: Development Step 4: Consensus Source: Author's representation. it is usually welcomed by all. This step involves the incorporation of the new evidence into a new or currently existing clinical protocol. This final step involves measuring the effect of implementing the new evidence by auditing patient outcomes after implementation. Step 6: Implementation. Additionally. Validation . Although new research is exciting and often quickly adapted to clinical practice. Step 5: Development. Placing the risks and benefits into perspective will facilitate an understanding of new evidence.. development is usually performed by a multidisciplinary team that likely includes a pharmacist. validation of research is extremely important. Feedback is used to augment or revise the implementation. If new evidence clearly provides a great benefit with very little risk. in that new evidence is constantly generated. 27 . This step occurs immediately following development. More controversy usually arises when the risk-to-benefit ratio is not as dear. Thus. Evaluation of Clinical Trials That Validate Treatment Usefulness Research enhancing patient outcomes can greatly improve clinical practice. Pharmacists should monitor important guidelines that apply to their practice area. or order set. it can identify ways to improve the implementation prbcess. In the hospital setting. They should help inform other health care practitioners when updates or new guidelines are published. members of the development team are usually available to help with troubleshooting any problems with the new evidence. Following the initial education. ~ Step 7: Assessment. Implementation includes education of all health care practitioners involved in applying the new evidence to the patient. pathway. The pharmacist's role in acceptance is to highlight the risks and benefits and discuss them with other pertinent health care professionals.. Step 4: Consensus. Although not all evidence will be incorporated.3. !i!ll ~ ~ l1lli be applied directly to patients. Step 3: Acceptance.Practice Guidelines and Clinical Trials 4 27-2. Whether new evidence is accepted depends highly on the quality of the evidence. An important part of the assessment phase is providing feedback to the development team. continual monitoring of newly published evidence is essential to ensure that patients receive the most effective care. Pharmacists may be the practice leader or they may assist other leaders in this process. To achieve consensus. results should be confirmed in independent study to ensure that the initial results were true. The entire process is circular. such as providing enhanced education or awareness raising.

It is impossible to conduct a randomized controlled trial evaluating the numerous recommendations provided in the practice guidelines. Following this study. Unfortunately. two factors often prevent clinicians from confidently implementing promising results: fiffi Lack of validation studies. Numerous examples show significant research results being confounded by subsequent studies unable to validate the original results. meaning that one study shows improved patient outcomes and is validated by a different single study. prospective observational study of 59 intensive care units (ICUs). . The study documented a decrease in mortality of 16%. The researchers investigated the association between five recommendations in the clinical practice guidelines and adequacy of enteral nutrition. Despite the difficulties with validating original research. a different group of researchers investigated the use of the goaldirected therapy from the original study. clinicians have more confidence that the improved outcome is indeed a real effect. These guidelines systematically review the pertinent literature regarding the topic and provided clinicians a set of recommendations. the clinician needs to evaluate the risk-to-benefit ratio of the new findings. these studies are essential to clinicians who want to ensure their patients receive the best evidencebased care available. A prime example is a study investigating the use of lowdose steroids in patients with septic shock. with the increased use of clinical guidelines. However. For this scenario to occur. Researchers and clinicians rely on sound study design and statistical evaluation to provide confidence in the results obtained. The study concluded that ICUs more consistent with guidelines demonstrated more success with enterally feeding patients. The original study found improved mortality in certain patients receiving low-dose steroids. a validation study may be considered unethical. Ensuring that the results found in one study are correct can be difficult. Clinicians may believe so strongly in the benefit that a controlled trial may be considered as placing study subjects at unnecessary risk. Conflicting results in validation studies. a possibility always exists that the promising results occurred by chance or that some unknown factor contributed to the improved outcomes. clinicians have to monitor patients closely for the desired outcome and any potential adverse effects. This study validated theresults from the original research and allowed clinicians to apply the results to patients with confidence.The APhA Complete Review tor the Foreign Pharmacy Graduate Equivalency Examination® generally occurs on a single-study basis. especially if the validation uses a placebo-controlled arm. however. ~ Validation of clinical practice guidelines. Therefore. well designed. In 2003. studies are being published that validate the entire guideline: li!J Validation of a single study. An example is a study investigating early goal-directed therapy for hemodynamic support of patients with sepsis presenting to the emergency department. and the medical community supports the results. In 2004. the original study would have to be extremely well conducted. If a physician believes the original study results are convincing enough. Alternatively. he or she may prefer to withhold patients from enrollment in a validation study. The results from the second study have produced a dilemma for clinicians wanting to use low-dose steroids in their patients. One major barrier to the successful completion of a validation study is physician preference. If the new research is implemented. a validation of these guidelines was published. Following are the two main reasons for this difficulty: o If one study shows a significant benefit. and controlled and would need to have a sufficient study population. Some well-conducted single studies have such a great influence on the medical community that it is difficult or impossible to perform a validation study. the validation study was a multicentered. The physician may want to ensure his or her patients receive the therapy from the original study. Whether this treatment will benefit patients is now uncertain. These researchers were able to achieve a 9% reduction in mortality. If a separate study confirms the initial study's promising results. the Canadian clinical practice guidelines for nutrition support in critically ill patients receiving mechanical ventilation were published. a large multicentered study was unable to confirm the mortality benefit identified in the initial study. When new research has not been validated. a multitude of well-conducted smaller studies can demonstrate similar results. hoping that they will receive the benefit originally found. Unfortunately.

000 publications.:. B. The lack of a standardized grading scale in clinical practice guidelines makes it extremely important that the reader first determine how recommendations were developed..J t:iJ ~ &J !!tl ~!.:I:2::. Clinical studies fall into two major categories: treatment and observational. D. B. and assessment.000 publications. 6. Seven steps are taken to apply clinical practice guidelines to patient care: new evidence.2:. What is the difference between a clinical practice guideline and a review? A.000 publications. Validation studies have begun to demonstrate the usefulness of applying clinical practice guidelines to patient care. Reviews provide recommendations that are specifically designed to guide patient care. 4.060 guidelines from 289 organizations worldwide. dissemination. A clinical practice guideline contains text describing the literature that supports the provided recommendations. consensus. Evidence-based medicine approaches a clinical dilemma as an answerable clinical question. 27 .000 publications. The Cochrane Collaboration was developed to provide regularly updated reviews of clinically important questions. C.'!'7ITL~~"'. D. Reviews have a broader scope than clinical practice guidelines.000. B. A quantitative method of combining the results of multiple independent studies and synthesizing the results to arrive at a conclusion about the specific question studied D. 5m Questions A. A nonquantitative review of the literature 5. C. Clinical practice guidelines provide recommendations that are specifically designed to guide patient care. Which study design is considered the most statistically rigorous? 7. D. Key Points $"" •. The AGREE Instrument consist of 23 items organized into six different sections and is used to evaluate the quality of clinical practice guidelines.:::. development. A. Medically related literature published each year consists of approximately 1. 50. The National Guideline Clearinghouse Web site (www.] !ilil !ill ~~3 u:i1 1'1 !l1l 2.Practice Guidelines and Clinical Trials 27 .rr. implementation." A staggering volume of medical literature is published yearly. 750. acceptance. A clinical practice guideline generally consists of abbreviated text containing a recommendation for quick reference by the clinician. have no effect on bias. Which organization is best known for developing meta-analyses for important clinical conditions? A. increase bias in the study. Use of blinding in a clinical trial is expected to Which of the following best describes a meta -analysis? A. Cohort Case control Randomized Cross-sectional A. controlled trial.. 3. Evidence-based guidelines provide the strength of a recommendation based on the quality of the supporting literature. :'J'. C. Cochrane Collaboration National Meta-Analyses Group International Society for Meta-Analysis National Library of Medicine Which methodological approach to patient care looks at clinical dilemmas as answerable clinical questions? . D.. C. decrease bias in the study.·::<~' ~-. increase and decrease bias in the study. A qualitative method of combining the results of multiple independent studies and synthesizing the results to arrive at a conclusion about the specific question studied B. C. The most statistically rigorous clinical trial design is the blinded. 5. Validation studies are essential for confirming original research findings. 1. randomized.gov) contains 3.' !ilil Eill ll. B.guideline. B. D. There is no difference between a review and clinical practice guideline. A single-center independent study C. 4.

B. A methodological review of the literature is performed for evidence-based guidelines.060 guidelines from 289 organizations worldwide? How do evidence-based clinical practice guidelines differ from traditional clinical practice guidelines? A. 60 D. A. Traditional clinical practice guidelines are published only online. B. Recommend implementing the recommendation. D. D. 45 c. Nationally renowned experts develop evidence-based clinical practice guidelines. D.1 12. B. C. D. Medical decision making Decision analysis Evidence-based medicine Standard medical analysis C. 9. Which of the following sections of clinical practice guidelines are most important to pharmacists? A.~I~~»I' The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination® A. D. D.25% I 17. 4 B. C. If three users evaluate five items in an AGREE Instrument section. Introduction Diagnosis Future research Therapy 10.org www. 17% c. If the maximum possible score for an AGREE Instrument section is 64. Traditional clinical practice guidelines provide recommendations that are more specific. what is the standardized score? A. If a clinical practice guideline provided a recommendation supported by a well-conducted randomized controlled trial. 83% B. what is the maximum possible score for that section? A. www. B. Which of the following Web sites contains 8.guideline. Acceptance Consensus Assessment Implementation . 14. Patients Hospital policy makers Patients' families No one 15.org www. Which of the following is a rationale for incorporating clinical practice guidelines into patient care? A. 3 D. 3. what are the experts likely recommending? A. C. B. 13.myguidelines.gov www.gov Which of the following groups should use the AGREE Instrument? A. the minimum possible score is 16. what number would it likely be graded? A. 5 c. If a clinical practice guideline provided a D recommendation. C.cdc. To change policies of medical insurers 11. What is the general purpose of sample clinical pathways used in practice guidelines? A. B. B. D. D. and the obtained score is 56. Consider implementing the recommendation. To reduce thinking by clinicians D. To dictate exact care provided in the pathway B. B. To provide a foundation for customized pathways C.medmatrix.100 16. To To To To reduce physician independence increase medical errors increase physician independence reduce medical errors 18. Which of the following is the last step in incorporating clinical practice guidelines into direct patient care? A. 10 B. C. C. Consider not implementing the recommendation. C. 50% D. Recommend not implementing the recommendation.

. B.minimum score). 6. A. 13. Validation studies duplicate (to some degree) an original study that shows benefit to determine if the benefit can be reproduced. dissemination. The Web site of the National Guideline Clearinghouse. 15. This is acceptable and sometimes preferred. D. consensus. www. Thus. B. A. there are 20 possible points per reviewer because each item has a maximum score of 4. Adapting guideline pathways to local care is very important to address the most effective approach to patient care. C. 2. Which of the following best describes a validation study? A. Guidelines generally use a lower number to represent a strong grading. If all three reviewers provide the maximum score on each item. Confirmation of original research by an independent group C. Only evidence-based guidelines can ensure that a 9. However. 5 x 4 = 20. A. clinical Intervention. Searching MEDLINE by 1-year increments produces approximately 750. Similar to grading. 3.83 X 100 = 83%. D. C. Clinicians prefer to wait until a study has been validated before automatically implementing the studied intervention into clinical practice. 6e Answers 1.gov. Original research not previously reported B. 5. Comparison with at least one alternative. 20. implementation. 16. A review compiles and synthesizes information about a topic. Many local pathways will differ from those provided in guidelines. The Cochrane Collaboration was established specifically to conduct meta-analyses. and clinical Outcome) A. 4. Blinding reduces bias in the study by preventing those conducting the study to influence the outcomes of the study. The seven steps are new evidence. they may not pertain to pharmacists as much as the section covering therapy. Validation studies are important to help determine if the beneficial effect is true or just occurred by chance. and assessment. B. D. A. Recommendation by a clinical expert 20. D. hospital policy makers should be able to grade the strength of a guideline. methodological review of the literature was performed. The National Library of Medicine is the world's largest medical library and the other organizations are fictitious. but a practice guideline provides weighted recommendations that are designed to guide each aspect of care related to that topic. Although the sections addressing other issues are very important. 7. 18. Guidelines do not attempt to reduce or increase physician independence. it is multiplied by 100. D. D. C. Laboratory research supporting a clinical trial D.000 publications. The standardized score=f . there is a total of 60 points. assessment in the final step. 17. acceptance. Use of a randomized design decreases the likelihood for other factors to influence the outcome of a clinical trial. C. D.Practice Guidelines and Clinical Trials 19. (56 -16)/(64 -16) = 40/48 = 0. Lack of interest Lack of validation studies Confirmatory validation studies Incorporation into clinical practice guidelines 27 . Which of the following prevents clinicians from implementing new evidence in patient care? A.(obtained scoreminimum score)/(maximum score. 10. recommendations are usually less strong as they move through the alphabet. 12. Evidence-based medicine is based on the "answerable clinical question" and is represented by the mnemonic PICO (Patient's problem. 8. Clinical practice guidelines that are not evidence based often represent opinion. B. C. states that it contains such guidelines. thereby suggesting a true beneficial effect. C. Thus a recommendation of choice A is usually better than a recommendation of choice D. If there are five items. 3 X 20 = 60. The definition of a meta-analysis is a quantitative method of combining the results of multiple independent studies and synthesizing theresults to arrive at a conclusion about the specific question studied. Hence. 14. If this score is reported as a percentage. Thus. Pharmacists are medication experts. Thus. Neither patients nor their family members would use the AGREE document to evaluate practice guidelines. . B. The only beneficial answer is to reduce medical errors. 19. 11. development. Medication therapy is the focus of all pharmacists.guideline.

53(1):142-64. et al. DeLong ER. Vist G. Bergqvist D. Lund B. Lohr KN. Health Serv Res. Singh I\-P. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. J Trauma. ]AMA. 1995. Early goaldirected therapy in the treatment of severe sepsis and septic shock. 1992:346-410. et al. Drover JW. Users' guides to the medical literature: VIII. numbers.336(7):480-86. Dhaliwal R. 2008. Charpentier C. Annane D. 2002. Washington. Practice management guidelines for the prevention of venous thromboembolism in trauma patients: The EAST practice management guidelines work group. 2009. Mulla ZD. et al. et al. References AGREE Collaboration.61(9): 939-45. Racial variation in the use of coronary-revascularization procedures: Are the differences real? Do they matter? N Eng! J Med. 2002.C. Hayward RS. Lang Speech Hear Serv Sch. Pineo GF. Rivers E. 2004. Appraisal of Guidelines for Research & Evaluation (AGREE) Instrument. Focht A.The APhA Complete Review tor the Foreign Pharmacy Graduate Equivalency Examination® 27 . On the origins and development of evidence-based medicine and medical decision making. Best D. Day A. Sammer CE. Lohr KN.132(2):425-32.: National Academies Press. Geerts WH. Canadian clinical practice guidelines for nutrition support in mechanically ventilated.345(19): 1368-77. 2004.27(5):355-73. Chest. Annane D. Hydrocortisone therapy for patients with septic shock. To Err Is Human: Building a Safer Health System. Clinical pathway care improves outcomes among patients hospitalized for community-acquired pneumonia. American Society of Health-System Pharmacists. D. Dhaliwal R. Oxman AD. Guidelines for Clinical Practice: From Development to Use. Horton JM. Lykens K. Adler LM. Washington. 2004. JAMA.org. et al.39(3 ):289-302. D. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Hauck LD. Are the recommendations valid? The Evidence-Based Medicine Working Group.358(2):111-24. Shaw LK. Elstein AS. et al.14(9):669-75.32(11): 2260-66. and assessment of critical pathways. Geographic variation in the treatment of acute myocardial infarction: The Cooperative Cardiovascular Project. 2008.281(7):627-33. Validation of the Canadian clinical practice guidelines for nutrition support in mechanically ventilated. Available at: www .288(7):862-71. Sebille V. Heyland DK. Schiinemann HJ. How to use clinical practice guidelines-A. ASHP guidelines on the pharmacist's role in the development. Sprung CL. N Eng! J Med.43(2): 569-81. London.: National Academies Press. Am J Health-Syst Pharm. 2000. Rogers FB. Cipolle MD. Prospective external validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock. Velmahos G. Keh D. 2008. eds. Ann Epidemiol. 1999. Peterson ED. et al. Quinton HB. et al. 1997. Traven ND. Institute of Medicine. Jones AE. Griffer M. Tunis SR. Wilson MC. A provisional instrument for assessing clinical practice guidelines. N Eng! J Med. Havstad S. Field MJ.7. crit- ically ill adult patients: Results of a prospective observational study. implementation. Crit Care Med. Physician characteristics and the reported effect of evidence-based practice guidelines. In: Field MJ. AGREE Collaboration. critically ill adult patients. Letters.53(suppl2):S184-89. 2004.274(7):570-74. 2008. et al. 2003. ]AMA. Inflamm Res. J Parenter Enteral Nutr. symbols and words: How to communicate grades of evidence and recommendations. 2001. Kline JA. 2007.133 (Suppl6):381S-453S. Chest.. Heyland DK.agreecollaboration. . CMAJ. Hargrove P. et al. 2003.C. Nguyen B.169(7):677-80. O'Connor GT. Procedures for using clinical practice guidelines.