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Geriatric

Pharmacy Review
Module 19: Evalua9on & Use of Clinical Informa9on to Improve Pa9ent Care

Accreditation Information

ASCP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This home study web activity has been assigned 1 credit hour. ACPE UPN: 0203-0000-10-97-H04-P Release Date: 7/1/2010 Expiration Date: 7/1/2013

To receive continuing education credit for this course, participants must complete an on-line evaluation form and pass the online assessment with a score of 70% or better. If you do not receive a minimum score of 70% or better on the assessment, you are permitted 4 retakes. After passing the assessment, you can print and track your continuing education statements of credit online.

Geriatric Pharmacy Review courses have not yet been approved for Florida consultant pharmacy continuing education.

Copyright 2011 American Society of Consultant Pharmacists

Content Experts

H. E. Davidson, PharmD Editor-in-Chief, The Consultant Pharmacist & PartnerInsight Therapeutics, LLC

Faculty Disclosure: H.E. Davidson, PharmD discloses the following relationships: Speaker/Consultant for Abbott Labs, Sanofi-Aventis

Copyright 2011 American Society of Consultant Pharmacists

Evidence-Based Medicine and Clinical Studies

Learning Objectives:

By the end of this Review Concept you should be able to:

Define the concept of evidence-based medicine. Explain how levels of evidence are classified. Differentiate Type I and Type II errors of statistical interpretation. Explain the significance of the p value and confidence intervals in interpreting clinical studies. Describe measures of disease frequency and the use of risk and odds ratios in epidemiological studies. Differentiate prospective and retrospective study designs in terms of their statistical effectiveness, advantages and limitations. Cite examples of prospective and retrospective study designs. Differentiate the features of parallel and crossover randomized controlled trials. Describe the uses and principal features of multicenter study designs and meta-analyses. Describe study designs commonly used in epidemiological studies and provide examples of each. Define measures of disease frequency and effect commonly used in epidemiological studies.

Copyright 2011 American Society of Consultant Pharmacists

Assumptions of Evidence-Based Medicine

No single individual can know all that is needed to practice effectively across the spectrum of care Not all therapies or decisions applied in the health care setting have been properly validated Evidence-based medicine is a relatively new concept based on the recognition that no single individual can know all that is needed to practice effectively across the spectrum of care. It also acknowledges that not all therapies or decisions applied in the health care setting have been validated by objective evidence. Evidence-based medicine tries to address these concerns by involving clinical experts in the selection, review, and dissemination of relevant biomedical literature.

Copyright 2011 American Society of Consultant Pharmacists

Goal of Evidence-Based Medicine


To promote the conscientious, explicit, and judicious use of current best evidence in making patient care decisions in: Healthcare organizations Individual clinical practice

Evidence-based medicine is the foundation for the development of clinical pathways, practice guidelines, and treatment protocols. Using a collaborative, problem-solving approach, panels of clinical experts identify the most current clinical literature, then review it in an attempt to extract relevant healthcare applications. Their goal is the conscientious, explicit, and judicious use of current best evidence to standardize decisions about the care of individual patients.

Copyright 2011 American Society of Consultant Pharmacists

Levels of Evidence
Level I (A):Randomized trials with study designs that minimize the probability of Type I or Type II errors Level II (B):Randomized trials with study designs that have a high probability of Type I or Type II errors Level III (C):Nonrandomized concurrent cohort comparison between patients who did and did not receive therapy Level IV (D):Nonrandomized historical cohort comparison between current patients who received the therapy and former patients who did not Level V (E):Case series without controls

Evidence-based medicine explores the entire spectrum of research. Based on the methods used and their statistical reliability, clinical studies are assigned to one of five levels. Level I or level A studies use methods that provide the most reliable evidence. Often, they are placebo-controlled, double-blind trials that are virtually bias-free. Level V or level E studies used methods that provide the least reliable evidence.

Copyright 2011 American Society of Consultant Pharmacists

Types of Errors

Type I (alpha):Concluding that the therapy had an effect when it did not Type II (beta):Concluding that the therapy had no effect when it did

The difference between the first and second levels of evidence is based on the probability of Type I and Type II errors. Since research and statistics are not exact sciences, there is always a danger of drawing a wrong conclusion from the available data. A Type I error, also called an alpha error occurs when we say there is a statistically significant difference between groups when in fact there is not. A Type II error or beta error occurs when we say that there is no significant difference between groups when in fact there is. The possibility of Type I or Type II errors is one of the main reasons that the replication of studies completed by several investigators is encouraged.

Copyright 2011 American Society of Consultant Pharmacists

The P Value
The P value:the probability of being wrong when making assertions about statistical significance In biomedical literature, P < 0.05 is used for statistical significance The smaller the P value, the less the likelihood of making a Type I or Type II error

To decide whether a result is statistically significant or not, a probability value is established, called the p value. The p value is the probability of being wrong when making assertions about statistical significance. The smaller the p value, the less the likelihood of making a Type I or Type II error. For biomedical research, the p value of less than or equal to zero point zero five is considered the standard. A p value of zero point zero five or less means that there is a statistically significant difference between the two groups being compared.

Copyright 2011 American Society of Consultant Pharmacists

Confidence Intervals
Confidence Interval (CI):the probability that the value of a given parameter is included within a particular ranges of values In biomedical literature, a 95% confidence interval is considered the norm

Confidence intervals (CI) are calculated to provide a range of reasonable values that contain a parameter of interest, such as an outcome variable or a population mean. The confidence interval is usually expressed as a percentage; in the biomedical literature, this percentage is usually ninety-five percent. A ninety-five percent confidence interval tells us that the true value is in the interval ninety-five percent of the time. The confidence interval provides information not provided by the p value in that it reports information in terms of the measurements actually used. The width of the confidence interval gives an indication of the real information provided in the study. A wide confidence interval indicates lower precision of the statistic, and a narrow confidence interval indicates high precision. If the confidence interval contains the null value, (i.e., 1 as in the case of odds ratios or risk ratios) the interval shows no statistically significant difference. Together, the p value and confidence interval provide more useful information than either could convey alone.

Copyright 2011 American Society of Consultant Pharmacists

Research Designs Frequently Used in Pharmaceutical Research


Prospective: Randomized controlled trials (parallel and crossover) Longitudinal studies Multicenter studies Cohort studies Case-control studies Retrospective: Meta-analyses Case-control studies Chart reviews and historical research Cross-sectional or prevalence studies Cohort studies Epidemiological: Cohort studies Case-controlled studies Cross-sectional or prevalence studies Pharmaceutical research employs a variety of study designs. With respect to clinical drug trials, two designs in particular are seen most often: prospective and retrospective designs. Each of these study designs has its own advantages and limitations, and its own unique role in clinical research. Epidemiological study designs are useful to the medical community in evaluating the effects of various exposures on morbidity, mortality, and other outcomes.

Copyright 2011 American Society of Consultant Pharmacists

Prospective Clinical Studies


A potential source of Level I quality evidence Forward looking Data is collected at some future time Good for studies where subjects are readily available More powerful statistically because bias is reduced through the selection of valid and reliable research methods More expensive and difficult to complete

Prospective studies are a superior source of research data, providing level one quality evidence when properly designed and executed. Examples include randomized controlled trials and longitudinal studies. Prospective studies look forward in time, in the sense that the data for analysis will be generated at some future time when the research design is implemented. Prospective research designs are statistically powerful because bias can be reduced to a minimum through the use of randomized subject selection, double blind techniques, and placebo controls. Prospective designs are also expensive and can be difficult to complete.

Copyright 2011 American Society of Consultant Pharmacists

Parallel Randomized Controlled Trials

Because they are statistically powerful, prospective research designs such as randomized controlled trials are frequently seen in the pharmaceutical literature. There are two principal types of randomized controlled trials: parallel and crossover. In the parallel study design, two or more independent study groups receive different pharmacologic treatments.

Copyright 2011 American Society of Consultant Pharmacists

Crossover Randomized Controlled Trials

In crossover randomized control trials, each subject receives all of the treatments that are under study. Subjects are initially divided into experimental and control groups, then switched later in the study. Statisically, crossover trial design is a much more sensitive research design because variability between subjects is reduced. Another advantage of the crossover design is that fewer subjects are needed. One disadvantage of the crossover design is the carryover effect: the possibility that subjects who switch from therapeutic to placebo group may experience lingering effects of treatment. Also, crossover randomized control trials are not as effective for studying medical conditions that change over time, since it is difficult to separate the effects of treatment from the disease process itself.

Copyright 2011 American Society of Consultant Pharmacists

Multicenter Trial Designs


Rapid patient recruitment Less single investigator bias More interpatient variability and confounding factors

Multicenter trial designs are popular among large pharmaceutical companies because it allows a large number of subjects to be recruited in a short period of time. By conducting identical trials in multiple settings, multicenter designs provide a way to collect statistically meaningful data when it is infeasible to locate sufficient test subjects in any single setting. Also, because several investigators are involved in data collection, the risk of investigator bias is reduced. However, the involvement of multiple investigators may also introduce subtle variations in trial administration and data collection techniques, even if all investigators are using the same tools and protocols. This problem may not be significant if a large number of subjects are being studied.

Copyright 2011 American Society of Consultant Pharmacists

Retrospective Clinical Studies


Quality of evidence is variable Backward looking Data is collected from past events Good for studies where subjects are hard to find or ethical constraints prohibit prospective study Less powerful statistically because there are fewer controls on data collection tools and techniques Less expensive and easier to complete

In contrast to prospective studies, retrospective studies look back in time to collect data about events that have occurred sometime in the past. Examples include case-controlled studies, chart reviews, and historical research. Retrospective studies tend to be more biased because there is less control over data collection tools and techniques. There is always some uncertainty about the reliability of the data. In spite of these limitations, retrospective studies do have their place in the literature. They are useful in conducting studies that are almost impossible to do prospectively, as when studying rare diseases that affect only a small percentage of patients. They are also useful in situations where it is unethical to do a double-blind placebo controlled trial, such as testing a new drug for heart attack or stroke. Because they are less expensive to conduct, retrospective studies are often the initial step in conducting prospective studies and for generating research hypotheses. Using historical data, a retrospective study can help determine whether there is sufficient support of the research hypothesis to justify the expense of a more controlled, prospective study.

Copyright 2011 American Society of Consultant Pharmacists

Meta-Analyses
Combine statistical data from previous research studies Evaluate studies that measure the similar outcomes, test populations and research techniques Increase the statistical power of randomized controlled trials based on small subject populations

One retrospective study design that has become popular in recent years is the meta-analysis. Meta-analyses are useful because they mitigate the statistical limitations of studies based on insufficient numbers of test subjects (i.e., sample size) .By combining these studies into a meta-analysis, investigators are able to create one large study with enough subjects to provide meaningful statistical data. Prerequisite to this, the investigators must precisely define the criteria for selecting studies for meta-analysis. By controlling for variations in subject age, research method, and other variables, investigators can be sure they are combining apples with apples, not apples with oranges.

Copyright 2011 American Society of Consultant Pharmacists

Cohort Studies
Compare the occurrence of given outcome in two or more groups which differ in their exposure to potential causes of the problem e.g., Framingham Study of cardiovascular disease

Epidemiological study designs include cohort studies, case-control studies, and cross-sectional studies. In a cohort study, an investigator compares the occurrence of a given outcome, such as a disease, in two or more groups of people who are initially free of the outcome and differ in their exposure to potential causes of the problem. The Framingham Study of cardiovascular disease, begun in 1948, is one of the best-known cohort studies. The association of elevated blood cholesterol and an increased risk of coronary heart disease is one of the hypotheses tested in this study.

Copyright 2011 American Society of Consultant Pharmacists

Case-Control Studies
Compare cases and noncases of a given outcome in terms of their exposure to potential causes e.g., Studies investigating the association of NSAIDS and PUD e.g., Disease outbreak investigations

In case-control studies, cases and noncases of a given outcome are compared in terms of their exposure to potential causes. The association between nonsteroidal anti-inflammatory drugs and peptic ulcer disease has been established almost exclusively through case-controlled and cohort studies. The Centers for Disease Control and Prevention (CDC) also frequently uses case-control studies to investigate disease outbreaks, such as food-borne illness.

Copyright 2011 American Society of Consultant Pharmacists

Cross-Sectional Studies

Evaluate an entire population in terms of its exposures and the occurrence of a given outcome or disease e.g., Studies of issues relating to entire nursing facility populations

Cross-sectional studies are studies examine the relationship between outcomes, such a disease or event, and other variables of interest in population of individuals. The cross-sectional study is an epidemiologic study design that consulting pharmacists might use to evaluate issues such as the prevalence of a condition in nursing facility populations and related factors. For example, the proportion of residents who had a fall in a given period of time and were also receiving antipsychotic therapy. Cross-sectional studies cannot determine causal association but can determine prevalence, hence, some use the term prevalence study as one type of cross-sectional study.

Copyright 2011 American Society of Consultant Pharmacists

Measures Commonly Used in Epidemiological Studies


Measures of Disease Frequency: Incidence: Number of new events or cases during a specific time period Prevalence: The number of events (not necessarily the first occurrence of the event)

Measures of Effect: Risk ratio: Comparison of the risk in exposed versus unexposed cases or a baseline Odds ratio: An alternative measure where the incidence of the event is unknown, such as in a cross-sectional or case-control study; an estimation of the risk ratio

Copyright 2011 American Society of Consultant Pharmacists

Measures Commonly Used in Epidemiological Studies

Epidemiological studies use measures of disease frequency and measures of effect to describe phenomena being investigated. One measure of disease frequency, incidence, measures the number of new events (also referred to as incident cases) during a specific time period. Time is an essential component of incidence. Prevalence is a measure of the presence of an event, but not necessarily the first occurrence of the event. One of the most useful measures of prevalence is point prevalence, which is the proportion of individuals with the condition at the given point in time. In cohort studies, case-control studies, and prevalence or cross-sectional studies, these measures are referred to as risks. The risk ratio is the comparison of the risk in exposed cases to the risk in unexposed cases or a baseline. The risk ratio is one-point-zero if the probability is the same for the two groups (i.e, equal incidence). If the risk ratio is five-point-zero, then the cases are five times more likely than the control group to have the outcome in question. Odds ratio is used as an alternative to the risk ratio in studies where the actual incidence of the event is not known. It is commonly used in case-control or cross-sectional studies when prevalence is known.

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Resources
For additional information, see: Freeman, J.(1996).Quantitative epidemiology. Infection Control and Hospital Epidemiology; 17:249-255. Hennekens, C. H. & Buring, J. E. (1987). Epidemiology in medicine. Boston: Little, Brown & Co. Kelsey, J. L., Whittemore, A. S. & Evans, A. S.(1996). Methods in observational epidemiology, 2nd ed.New York:Oxford University Press. Last, J. M.(1995). Dictionary of epidemiology, 2nd ed. New York:Oxford University Press. Riffenburgh, R. H. (1999). Statistics in medicine. San Diego: Academic Press Rothman, K. J. & Greenland, S.(1998).Modern epidemiology, 2nd ed. Philadelphia:Lippincott-Raven. Sackett, D. L., Straus, S. E. Richardson, W. S., Rosenberg, W., Haynes, R. B.(2000).Evidence-based medicine, 2nd ed.New York:Churchill Livingstone. Sackett, D. L., Haynes, R. B. & Tugwell, P. (1991). Clinical epidemiology: A basic science for clinical medicine, 2nd ed. Philadelphia:Lippincott-Raven. Centre for Evidence-Based Medicine Research Methods Knowledge Base: RuralNet Evidence Based Medicine Data Source:

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Evaluating Clinical Studies


Learning Objectives:

By the end of this Review Concept you should be able to: Define the concept of validity, and describe its significance in evaluating the quality of clinical research. Differentiate between internal validity and external validity. Explain how the title, abstract, and introduction for a given research study can help evaluate the quality of the information presented. Cite criteria for evaluating the quality of the methods, results, discussion and conclusions described in a given research study. List questions to ask when evaluating the quality of a review article.

Copyright 2011 American Society of Consultant Pharmacists

Determining What to Read

Which journals? Which textbooks? Which online resources?

The review and evaluation of clinical literature is critical to the practice of Geriatric Pharmacy. It is through the use of such literature that the clinician maintains current pharmacological knowledge and awareness of the latest developments in the field.. Because the volume of biomedical and pharmaceutical studies now available is so overwhelming, Geriatric Pharmacists must be very selective in what they read. They must also be confident in the integrity of the data and conclusions drawn from such studies before applying them in the clinical setting.

Copyright 2011 American Society of Consultant Pharmacists

Establishing Validity: Questions to Ask


Is the hypothesis valid? Is the study design valid? Are the methods for data collection and analysis valid?

When reviewing a clinical study, the first question that must be asked is whether the research is valid. Validity is an index of how well a test or procedure measures what it is intended to measure. In other words, it describes the adequacy or effectiveness of a design, a procedure, or a measurement in achieving a specific purpose. Begin by asking yourself, is the hypothesis of the study valid? Is the study design valid? Are the methods used to collect and analyze the data valid? If your answer to any of these questions is no, the value of the study and the information within it must be suspect.

Copyright 2011 American Society of Consultant Pharmacists

Internal Validity and External Validity


Internal validity: How accurately the studys conclusions describe what actually occurred External validity: The generalizability of the study or its conclusions to larger populations represented by the study sample

When discussing validity, it is important to distinguish between internal validity and external validity. Internal validity refers to how well the study was conducted and how accurately the conclusions reflect what actually occurred in the study. External validity refers to the generalizability of the study or appropriateness of applying the conclusions to larger populations represented by the study sample. Keep in mind that in general randomized clinical trials have the best internal validity but may or may not have good generalizability. Cohort studies, on the other hand, tend to have good generalizability, but depending on how well they were conducted, may have issues with internal validity.
Copyright 2011 American Society of Consultant Pharmacists

Establishing Validity: Measurement Tools

Have measurement tools been validated?

The concept of validity is especially important when reviewing pharmaceutical studies. The validity of drug concentrations, for example, is based on the accuracy and precision of the assay methods used to determine blood concentrations. Have the methods of assay been published and validated? If so, have appropriate citations been included in the study? If the assay method is relatively new, have the investigators provided sufficient data in the study to establish its validity?

Copyright 2011 American Society of Consultant Pharmacists

Establishing Validity: Investigator Expertise


Are the investigators experienced with the methods used?

The validity of clinical information collected or presented in the study also depends on the expertise of the investigators using the selected assay methods. For example, if the study uses HPLC to determine drug concentrations, do the investigators have expertise in HPLC? This issue should also be addressed in the Methods section of the study. Other examples include the use of a validated instrument to screen for chronic diseases, such as dementia. Use of an unknown, unvalidated instrument would make the results suspect and without generalizability.

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Evaluating Clinical Studies: Title of the Study


Appropriate: A Cross-Sectional Study of Antidepressant Use In Medicaid Recipients Prescribed Antihypertensive Agents

Inappropriate: Increased Antidepressant Use In Patients Prescribed Beta-Blockers

Judging the quality of a clinical study can begin with the title. The title should state the purpose of the study, not a conclusion. Conclusions stated in the title of a study preempt the readers own interpretation of the data and reveal potential bias. Other elements of a good title include: simple, short, and concise; indicates the study design; defines the scope of the study; and worded appropriately for the target journal audience.

Copyright 2011 American Society of Consultant Pharmacists

Evaluating Clinical Studies: Abstract

Abstracts are useful in screening studies for further reading; however, you should never stop with the abstract. Because the length of abstracts is predetermined and often quite limited, important data may be left out. Reading the abstract alone may give you an entirely different impression, perhaps even lead you to the wrong conclusion, than if you had read the study in its entirety.

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Evaluating Clinical Studies: Introduction


The introduction is important in evaluating the quality of the study, for it is in the introduction that the authors should state their hypothesis. Do they clearly state the question that they went out to study? Be wary of studies that appear to be written ad hoc, that is, designed more around the data collected than around a clear statement of purpose.

Copyright 2011 American Society of Consultant Pharmacists

Evaluating Clinical Studies: Methods


Perhaps the most crucial element in the evaluation of the clinical study is the Methods section. It is here that questions of validity and reliability are typically raised. The choice of data collection tools and methods may reveal sources of investigator bias in the study. At the very least, the study design and data collection methods should be explicit enough to allow other researchers to reproduce the study. If appropriate for the study design, it is also important to discuss how the sample size (or power) for statistical significance was chosen. In addition, the statistical tools used to test the stated hypothesis should be clearly defined, as well as the independent (potential) and dependent (outcome) variables. For research involving human subjects, the Methods section of the paper is also the best place to state whether the study was reviewed and approved by an Institutional Review Board and whether subjects provided informed consent.

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Evaluating Clinical Studies: Results

Check the Results section. Are all the subjects of the study accounted for? If not, ask yourself why. Did they drop out of the study? Or were they omitted to minimize confusing or conflicting data? Did the authors report results on the outcome (dependent) variables describing in the methods section? Also confirm that the results are consistent with the study hypothesis and the methods described by the authors .

Copyright 2011 American Society of Consultant Pharmacists

Evaluating Clinical Studies: Discussion

The Discussion section of the study is where the investigator explains how the reader should interpret the results of the study and the clinical implications of his or her findings. This section should state clearly what new information the study provides and compares the results with those of other published studies. The limitations of the study, including any sources of potential bias, should also be stated here, as well as its strengths and weaknesses.

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Evaluating Clinical Studies: Conclusions

Finally, consider the conclusions. Remember, data can be interpreted in different ways. To avoid discounting your own interpretation prematurely, formulate your own conclusions, and then read those of the authors. Do they differ significantly? Look for information regarding the need for future research due to limitations of the study. Does the information in the study really provide any new insights on the subject? Is the study generalizable to the population which you serve?

Copyright 2011 American Society of Consultant Pharmacists

Evaluating Review Articles: Questions to Ask


Were the questions and methods clearly stated? Was the search for relevant studies comprehensive? What criteria were used to select the studies reviewed? Was the validity of the primary studies assessed? Was the assessment of the studies reproducible and free from bias? Were variations in findings between studies explained? Were the findings of the primary studies combined appropriately? Were the reviewers conclusions supported by the data cited? Review articles should be read with the same critical eye as primary studies. Are the questions the authors wish to address, and the methods for addressing them, clearly stated? How comprehensive was the authors search for information? What studies did they consult, and how valid and reliable were they? How did they determine which studies to include, and which to omit in their review? Did they provide a balanced perspective, reporting conflicting results and proposing explanations for the conflicts? If studies were combined, were they combined appropriately? If these questions are not adequately answered, it is difficult to evaluate the bias of the research or the validity of the authors conclusions.

Copyright 2011 American Society of Consultant Pharmacists

Resources
For additional information, see: Beeler, M. F.(1986). How to analyze clinical research reports. Chicago:American Society of Clinical Pathologists. Byrne, D. W. (1998).Publishing your medical research paper.Baltimore, MD:William &Wilkins. Elwood, J. M. (1998). Critical appraisal of epidemiological studies and clinical trials, 2nd ed.New York: Oxford University Press. Manly, B. J. (1992). The design and analysis of research studies.Cambridge, MA:Cambridge University Press. Marubini, E., Grazia, V., Valsecchi, M. G. & M. Emmerson.(1995).Analyzing survival data from clinical trials and observational studies.New York:John Wiley & Sons Spilker, B.(1991). Guide to clinical trials. Philadelphia:Lippincott-Raven. Spilker, B. & Schoenfelder, J.(1989). Presentation ofclinical data. Philadelphia:Lippincott-Raven. Thompson IM et al.The influence of finasteride on the development of prostate cancer.NEJM.2003;349:215-224.

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Use of Practice Guidelines


Content Expert H. E. Davidson, PharmD, MPH Assistant Professor, Clinical Internal Medicine Eastern Virginia Medical School Partner, Insight Therapeutics, LLC Norfolk, VA By the end of this Review Concept you should be able to: Trace the historical development of practice guidelines, including key legislation and organizations involved Describe the principal intent of practice guidelines Describe how practice guidelines are developed Explain why practice guidelines are not universally implemented Outline proposed recommendations to making geriatric practice guidelines more readily available to clinicians List sources of practice guidelines Describe the limitations of practice guidelines, based on the method in which they were developed

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A Brief History of Practice Guidelines


Informal guidelines based on expert opinion have been used since the beginning of the medical profession Formal guidelines were first introduced in 1983 when HCFA (now CMS, since 2001) contracted with peer review organizations (PROs) to review Medicare practices The OBRA Act of 1989 established AHCPR (now AHRQ, since 1999), which began developing guidelines based on scientific evidence In 1992, HCFA and the PROs moved from case-based review to the development of clinical paths

Practice guidelines have existed as long as the profession of medicine, since Hippocrates first wrote the physicians oath. For the most part, practice guidelines since then have been informal, based on the subjective opinions of experts in the field.

Copyright 2011 American Society of Consultant Pharmacists

HCFA and Peer Review Organizations (PROs)


To monitor health care quality by looking for: Common medical mistakes Appropriateness of procedures Adverse outcomes and possible causes

When Peer Review Organizations were introduced in the early eighties, the Health Care Financing Administration (now CMS) began to contract with them to provide quality assurance within Medicare. Every three years since 1983, a new scope of work was issued to these PROs. Initially, the work involved reviewing a sample of patient charts to find common medical mistakes, to evaluate the appropriateness of procedures, and to investigate adverse outcomes. The work of PROs continues now with Quality Improvement Organizations (QIOs)

Copyright 2011 American Society of Consultant Pharmacists

The Agency for Healthcare Research and Quality (AHRQ) (formerly AHCPR)
Established under the OBRA Act of 1989 Created to develop clinically relevant practice guidelines based on scientific evidence Supported by a health care environment characterized by: Spiraling medical costs Regional variations in practice Increasing competitiveness among managed care institutions

In 1986, the Institute of Medicine reported on the quality of care in nursing facilities. The report led to the Omnibus Budget Reconciliation Act of 1987 (OBRA 87). Under the OBRA Act of 1989, and amid pressure to reduce spiraling medical costs associated with Medicare and Medicaid, Congress established the Agency for Health Care Policy and Research. Their mission: to develop clinically relevant practice guidelines based on objective scientific evidence. The AHCPR evolved into the Agency for Healthcare Research and Quality (AHRQ) in 1999. AHCPR published guidelines from 1992 through 1996 on a variety of conditions, and since 1999, AHRQ continues with the development of evidence reports and technology assessments through designated Evidence-Based Practice Centers (EPCs). They also provide a repository of clinical guidelines published by other organizations at www.guideline.gov/

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From Case-based Review to Clinical Paths


In 1992, the HCFA changed its quality assurance approach from case-based review to clinical paths. PROs were expected to draw on demographic and patient billing databases to identify patterns of care that did not conform to the norm. The PROs were also asked to develop patient care algorithms to define standards of care. In 2002, PROs became Quality Improvement Organizations (QIOs) with a similar charge, and that is to review certain health care services furnished under Title XVIII of the Act (Medicare) and certain other Federal programs to determine whether those services are reasonable, medically necessary, provided in the appropriate setting, and are of a quality that meet professionally recognized standards.

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Goals of Practice Guidelines


1. To provide recommendations for clinical practice to improve patient outcomes and/or the cost-effectiveness of care 2. To mitigate the variability in practice that has been documented nationally by standardizing clinical procedures

The intent of the practice guidelines that have evolved through this process are two-fold. First, they provide recommendations for clinical practice to improve patient outcomes and/or the cost-effectiveness of care. Second, they mitigate the variability in practice that has been documented nationally by standardizing clinical procedures. Despite these benefits, however, universal acceptance of practice guidelines has not been achieved . Health care payers in some settings are requiring compliance with selected aspects of practice guidelines in order to receive the highest level of reimbursement. These so call pay-for-performance initiatives are also under consideration by Medicare.

Copyright 2011 American Society of Consultant Pharmacists

How Practice Guidelines Are Developed


Informal consensus Formal consensus Evidence-based Explicit guideline development

Clinical guidelines are developed using a variety of methods. Informal consensus relies on the opinions of experts. Formal consensus solicits these opinions using a more structured format. Evidence-based guidelines are based on a review of the clinical literature, whereas explicit guideline development uses a combination of objective evidence and expert opinion.

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Strength of Evidence Rating


Organizations use a variety of methods to weigh the evidence used in developing a practice guideline. The American College of Chest Physicians (ACCP) uses a two-tiered approach to grading recommendations in their guidelines on the use of antihthrombotic therapy; clarity of risk/benefit (e.g., efficacy and safety) determines if it is a grade 1 or 2 recommendation, and A,B, or C rating is based on the methodological strength of the supporting evidence. Therefore a Grade 1A recommendation has a clear benefit versus risk proposition and is based on a number of randomized clinical trials (e.g., aspirin use during acute coronary syndrome).

Copyright 2011 American Society of Consultant Pharmacists

Strength of Evidence Rating

Copyright 2011 American Society of Consultant Pharmacists

Criticisms of Practice Guidelines


Intrudes on freedom of practice Preempts clinician training and experience Does not accommodate individual patient needs If not followed explicitly, may lead to denial of payment or malpractice suit

Some critics of standardized practice guidelines view them as intrusions on the freedom to practice. Such guidelines, they claim, preempt the training and experience of the clinician. Further, they do not always address the unique health care needs of individual patients. Fears about change, possible denial of payment, and malpractice suits have kept other clinicians from using practice guidelines. Some health care organizations, however, have already started basing payment on meeting certain quality benchmarks, often based on clinical practice guidelines. Medicare, as of late 2006, is also considering such a strategy, referred to as Pay-for-Performance and will be conducting demonstration projects in 2007

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Finding Guidelines for Older Adults: A 1992 Study


Purpose: To determine the proportion of guidelines that address the needs of older adults Method: Random sampling of guidelines included in the 1992 Directory of Practice Parameters Conclusion: Only a minority of practice guidelines contain information about older patients Recommendations: 1. Use an annotated algorithm approach to clinical guideline development (JAMA. 1992;267:3311-3314.) 2. Define limitations or special groups in each guideline 3. Make clinical guidelines more accessible

One of the problems facing gerontologists, geriatric pharmacists, and other clinicians is finding practice guidelines that contain information relevant to older patients. A 1992 study, which randomly sampled guidelines included in Directory of Practice Parameters, found that only a small minority of practice guidelines contain such information. This is ironic, considering that elderly adults are a growing population that accounts for the majority of Medicare expenditures. The study offered the three recommendations listed on your screen for increasing the availability of practice information relevant to older adults. In a more recent study (2005), investigators looked at how well Clinical Practice Guidelines (CPGs) for common chronic diseases addressed the issue of multiple comorbid diseases in older persons. The findings were not encouraging and the authors concluded that adhering to current CPGs in caring for elderly could have undesirable effects.

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Some Published Clinical Practice Guidelines Related to Geriatric Care


Hunt SA, Abraham WT, Chin MH et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult; a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2005;112: 154-235. http://www.americanheart.org/presenter.jhtml?identifier=3004550 The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. Chest 2004;126 (suppl 3). American Geriatrics Society, British Geriatrics Society, and American Academy of Orthopaedic Surgeons Panel on Falls Prevention Guideline for the Prevention of Falls in Older Persons. JAGS 2001;49:664672. http://www.americangeriatrics.org/products/positionpapers/Falls.pdf American Heart Association Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention. Secondary prevention of coronary heart disease in the elderly (with emphasis on patients > or =75 years of age): an American Heart Association scientific statement from the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation. 2002;105:1735-43.. Agency for Healthcare Research and Quality Clinical Information http://www.ahrq.gov/clinic/ Guidelines for Improving the Care of the Older Person with Diabetes Mellitus. California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes. JAGS 2003;51:S265-280. http:// www.americangeriatrics.org/products/positionpapers/JAGSfinal05.pdf Practice Guideline for the Treatment of Patients with Major Depressive Disorder. American Psychiatric Association. 2000 http://www.psych.org/psych_pract/treatg/pg/Depression2e.book.cfm

Copyright 2011 American Society of Consultant Pharmacists

Sources of Practice Guidelines


National Guideline Clearinghouse Cochrane Collaboration National Library of Medicine: MD Consult: American Medical Directors Association:

Practice guidelines may be found through a variety of sources, including the U.S government supported National Guideline Clearinghouse. Your local medical library may have additional information catalogued by subject. General search engines, including PubMed (Medline) and Google are also useful tools to locate guidelines. Many medical and related associations support the development and maintenance of guidelines for disease conditions of importance to their profession and either provide free access via their respective website or by purchase.

Copyright 2011 American Society of Consultant Pharmacists

Limitations of Guideline Development Methods


Informal consensus Not based on objective evidence Rarely considers cost and outcomes Not validated Formal consensus Not based on objective evidence Rarely considers cost and outcomes Not validated Evidence-based Not validated Explicit guideline development Not validated

When applying any practice guideline, it is important to keep in mind the special needs of the geriatric patient. It is also helpful to be aware of the limitations of practice guidelines, depending on the method used to develop them. For example, practice guidelines based on formal or informal consensus may be based more on personal opinion and experience than on objective evidence. They rarely address costs or outcomes. Evidence-based guidelines, while more grounded in research, are seldom validated prior to publication. This however, should not diminish their utility and would be impractical based on the evolving evidence in the medical field.

Copyright 2011 American Society of Consultant Pharmacists

Using Clinical Practice Guidelines


Ask yourself: Does the Practice Guideline make practical, clinically important recommendations? Is the guideline resistant to clinically sensible variations in practice? Were all important decision options and outcomes clearly specified? Was the evidence related to each decision option identified, validated, and combined in a sensible and explicit way? What is the strength of each recommendation? What is the impact of uncertainty associated with the evidence and values used in the Guideline? Is the primary objective of the Guideline consistent with your objectives? Are the recommendations applicable to your patients?

Before accepting a practice guideline on face value, it is important to critically review the recommendations. Ask yourself whether the recommendations are practical and clinically important. How strong is each recommendation, based on the quality of the investigation, the magnitude and consistency of positive outcomes relative to negative outcomes, and the relative value placed on different outcomes? What is the impact of uncertainty associated with the evidence and values used in the Guideline? In other words, what are the consequences if they are wrong? Finally consider the applicability of the recommendations to your practice. Is the primary objective of the guideline consistent with your clinical objectives? Are the recommendations applicable to the types of patients you treat?

Copyright 2011 American Society of Consultant Pharmacists

Improving Physician Compliance with Clinical Practice Guidelines


Education Feedback Participation by clinicians in efforts to bring about change Administrative rules Financial incentives Financial penalties

In addition to increasing your own awareness and use of clinical practice guidelines, it is worth considering how you might help improve physician compliance with such guidelines. Studies investigating the reasons for physician noncompliance with practice guidelines indicate that misclassification of patient risk levels, changes in the patients medical condition, and health care system inefficiencies are key. The literature also suggests that physicians are more likely to implement changes associated with a given guideline if it is delivered as risk information and indicates potential cost savings with no increase in mortality and morbidity. General methods for improving physician use of clinical practice guidelines are shown on your screen. In general, combination methods are more effective than single methods.

Copyright 2011 American Society of Consultant Pharmacists

Resources
For additional information, see: Ellrodt, A. G., Conner, L., Riedinger, M., Weingarten, S. Measuring and improving physician compliance with clinical practice guidelines. Ann Intern Med.1995;122:277-282. Sackett, D. L., Straus, S. E., Richardson, W. S., Rosenberg, W., Haynes, R. B.(2000).Evidence-based medicine, 2nd ed. New York:Churchill Livingstone. Taler, G.(1996). Clinical practice guidelines: Their purposes and use. J Am Geriatr Soc.1996;44:1108-11. Wilson, M. C., Hayward, R. S. A., Tunis, S. R., Bass, E. B. & Guyatt, G. Users guide to the medical literature: How to use clinical practice guidelines.JAMA.1995;274(20):1630-1632. Clinical Practice: American College of Physicians Guidelines and U.S. Preventive Services Task Force Recommendations. Snow V, Ed. American College of Physicians, Philadelphia, 2005.

Guidelines for the elderly on the web: American Geriatrics Society American Medical Directors Association American Psychiatric Association Association for Practitioners in Infection Control and Epidemiology Agency for Healthcare Research and Quality Clinical Information
Copyright 2011 American Society of Consultant Pharmacists

Medication Use Evaluations


Learning Objectives:

By the end of this Review Concept you should be able to:

Explain the purpose of medication use evaluations. Explain the processes within the medication use system. Describe the principal approach used to conduct medication use evaluations. Identify criteria and related clinical indicators for the selection of drugs to be studied in medication use evaluations. Compare and contrast prospective, concurrent, and retrospective medication use evaluations. Describe different ways in which the geriatric pharmacist can participate in medical use evaluations. List the kinds of data that are typically collected during a medical use evaluation. Describe the typical structure of a medication use evaluation report. List resources available to the geriatric pharmacist for the selection of criteria for medication use evaluations.

Copyright 2011 American Society of Consultant Pharmacists

Introduction to Medication Use Evaluation


MUEs can provide information on a: Specific medication Class of medications Specific disease Specific process (e.g., prescribing, dispensing, administering, monitoring) Specific patient outcome

Medication use evaluations are formal reviews authorized and conducted by organized health care systems. In contrast to the more traditional drug use reviews, medication use evaluations use a multidisciplinary approach involving prescribers, pharmacists, nurses, administrators, and other health care professionals. Furthermore, they involve all aspects of the medication use process. Medication use evaluations can provide valuable information on a specific medication or class of medications, a specific disease or patient outcome, or a medication process.

Copyright 2011 American Society of Consultant Pharmacists

Standards Mandating Medication Use Evaluations


Standard for Hospital and Long-term Care Settings: The organization evaluates its medication management system.(MM.8.10) Standard for Long-term Care Settings: The organization collects data about medication use. (PI.3.2.1)

Medication use evaluations were first described by the Joint Commission on Accreditation of Healthcare Organizations in 1992. By 1994, the process was required. Both the hospital and long-term care standards of the Joint Commission now contain standards mandating evaluation of medication use. The standard for long-term care settings is displayed on your screen. The intent of these standards is to ensure that all aspects of the medication process carried out by the organization are measured, although not necessarily at the same time. This includes prescribing or ordering, distributing, administering, and monitoring the effects on residents. Over time, the organization includes these processes in its measurement activities. As of the fall of 2006, MM 8.10 was under review for revisions; it is likely that the intent of the standard will remain.

Copyright 2011 American Society of Consultant Pharmacists

Goals of Medication Use Evaluations


Evaluate the effectiveness of medication therapy Promote the optimal use of medications by the organization Improve patient safety and outcomes Minimize the cost of medication therapy Identify areas for clinician and patient education Demonstrate caring and respectful attitude toward patient

You may ask yourself, why is it important to measure these medication processes? Medication use evaluations are conducted to evaluate the effectiveness of medication therapy, promote optimal use of medications by the organization, improve patient safety, and minimize cost. They also help in identifying areas where clinician and patient education is needed. Finally, medication use evaluations are a reflection of caregivers respect for and concerns about the well-being of each patient.

Copyright 2011 American Society of Consultant Pharmacists

Criteria for Selecting Medications for Review


Medications that: Are known or suspected to cause adverse drug reactions or interactions Are considered high-risk medications, as defined by JCAHO Have substantial negative impact on patient outcomes or cost if used below optimum dose Are used frequently Have a narrow therapeutic index Are expensive

The types of medications that are typically selected for review include those drugs that are known or suspected to cause adverse drug reactions or interactions. JCAHO in Standard MM.7.10 defines high-risk medications as medications involved in a high percentage of medication errors or sentinel events and medications that carry a high risk for abuse, error, or other adverse outcomes. Examples include medications with a low therapeutic index, controlled substances, medications not approved or recently approved by FDA, psychotherapeutic medications, and look-alike and sound-alike medications. JCAHO requires organizations to identify high-risk and high-alert medications used within the organization. Medications that are used frequently or are potentially toxic are also frequently selected for review. Medication use evaluation studies can be focused on preventing medication-related problems.

Copyright 2011 American Society of Consultant Pharmacists

Indicators that Suggest the Need for a Medication Use Evaluation

Adverse reactions / toxicity Signs of treatment failures Signs of increasing bacterial resistance Frequent pharmacist interventions regarding a specific medication or medication category. Nonformulary medications / increased expenditures on a medication Patient dissatisfaction

Indicators in the clinical setting that often trigger the need to conduct a medication use evaluation include treatment failures, increased pharmacist intervention and patient dissatisfaction.The use of nonformulary agents and increased medication costs are also relevant indicators.

Copyright 2011 American Society of Consultant Pharmacists

JCAHO Performance Measurement System


Examples of Core Measures Involving Medication Use Acute myocardial infarction - Aspirin within 24 hours after admission - Aspirin prescribed at discharge - ACE inhibitor prscribed at discharge for patients with left ventricular systolic dysfunction - Beta blocker within 24 hours after admission - Beta blocker prescribed at discharge The Joint Commission, as part of their accreditation process, requires hospitals to provide data on various performance measures. These data are aggregated by third party companies, called Performance Measurement Systems, who report the data to JCAHO. Many of these performance measures address medication use. As you can see in the example on the screen, medication use is a key component of the assessment of the quality of care a hospital or other health care setting is providing.

Copyright 2011 American Society of Consultant Pharmacists

Criteria Approval and Empowerment


MUE criteria approved and supported by medical staff Empowerment of individuals performing MUE The success of any medication use evaluation program depends on the use of criteria approved by providers. Once approved, the criteria are applied by empowered individuals, usually in the pharmaceutical services department.

Copyright 2011 American Society of Consultant Pharmacists

Methods for Conducting Medication Use Evaluations


Prospective Evaluations: Look forward in time Less biased More costly Concurrent Evaluations: Performed upon initiation of therapy Less biased More costly Retrospective Evaluations: Look backward in time More biased Less costly

Medication use evaluations may be prospective, concurrent, or retrospective. Prospective medical use evaluations look forward in time, when treatment will be implemented and the relevant data will collected for analysis. Concurrent evaluations are performed upon initiation of therapy but not necessarily prior to the first dose. Statistically speaking, concurrent or prospective evaluations are more powerful because variables can be anticipated and controlled, reducing bias to a minimum. Retrospective evaluations, on the other hand, look backward in time. Using clinical records and other sources, data are collected about events that have occurred sometime in the past. While less expensive to conduct, retrospective evaluations tend to be more biased and less reliable because there is less control over the data collection process..

Copyright 2011 American Society of Consultant Pharmacists

Processes Addressed by the Medication Use Measurement Team

Selection and procurement Storage Ordering and transcribing Preparing and dispensing Administering Monitoring the effects on patients

The Joint Commissions standard MM.8.10 describes an example in which the Medication Use Measurement Team develops a plan to systematically measure all four processes related to medication use. The six processes the team plans to measure include those listed on your screen.

Copyright 2011 American Society of Consultant Pharmacists

Medication Use Evaluations: The Pharmacists Role

Work collaboratively with other health care providers to develop criteria for medication selection Review individual medication orders against criteria Collect, analyze, and evaluate patient-specific data Interpret and report MUE findings Make recommendations based on MUE findings Provide information and education based on MUE findings Schedule follow-up to assure that corrective actions were successful

There are many ways in which geriatric pharmacists can participate in medication use evaluations. They can collaborate on the development of criteria for medication selection. They can review individual drug orders against that criteria, and collect, analyze and evaluate the patient data collected. They can also contribute to the interpretation, dissemination, and application of the findings. The Joint Commissions standard T-X-three-point-nine suggests that clinicians monitor therapeutic response, appropriateness of medication choice, frequency and route of administration, attention to therapeutic duplication, and consider patient-specific medication contraindications. Based on their expertise, pharmacists are expected to alert practitioners to potential adverse events and situations warranting further consideration.

Copyright 2011 American Society of Consultant Pharmacists

Data Collection for Medication Use Evaluations


Prescribing: Indications Contraindications Dispensing: Dose Interactions Administering: Timing Food incompatibilities Monitoring: Lab tests General Adverse effects Outcomes

Geriatric pharmacists are frequently involved in collecting data for medical use evaluations. Medication use is a multidisciplinary process indicator that incorporates all five components shown on your screen. Data is collected in the areas of prescribing, dispensing, administering, monitoring, and outcome. It is important to evaluate all components of the medication use process to ensure the prescribed therapy is optimized.

Copyright 2011 American Society of Consultant Pharmacists

Reporting the Results of Medication Use Evaluations


Background Objective Methods Results (narrative and graphic) Corrective actions with follow-up References

Geriatric pharmacists are often involved in the reporting of medication use results. Such reports provide background on the evaluation by explaining the rationale for drug selection and why the study was important. The objective and method for conducting the evaluation are described. Results are frequently documented in narrative and graphic form. Corrective actions are recommended and follow-ups to these actions are proposed. Pharmacist interventions in concurrent and prospective studies are documented, quantified, and reported.

Copyright 2011 American Society of Consultant Pharmacists

Medication Use Evaluations: Information Sources


Primary professional literature Practice guidelines Current reference texts (AHFS, USPDI) Published criteria Publications of other standards-setting bodies (JCAHO, NQF, CMS)

To be an effective participant in medication use evaluations, the geriatric pharmacist should know where to find the latest information on the medication being studied. The primary professional literature is the best source of information, although up-to-date reference texts can be useful. Criteria for selecting and evaluating medications can be found in the American Hospital Formulary Service Drug Information and the United States Pharmacopeias Drug Information for the Health Care Professional. Additional sources of published criteria include JCAHO, the National Quality Forum, and CMS, all of whom establish performance measures regarding medication use. The Beers criteria, a list of medications considered unsafe for use in the elderly, have been adopted my many organizations, including CMS, for medication use evaluations. Lastly, a few companies, such as Insight Therapeutics, publish pre-developed criteria sets.

Copyright 2011 American Society of Consultant Pharmacists

Resources
For additional information, see: Angaran DM.Quality assurance to quality improvement:Measuring and monitoring pharmaceutical care. Am J Hosp Pharm. 1991;48:1901-1907. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med.2003;163: 2716-24.. Gurtwitz JH, Soumerai SB, & Avorn J.Improving medication prescribing and utilization in the nursing home.J Am Geriatr Soc.1990;38:542-552. Gutshall EL, Davidson HE, & Davis SK.(1999).Medication use evaluation, 3rd ed. Norfolk, VA:Insight Therapeutics, Inc. Mutnick AH, Sterba KJ, Peroutka JA, et al.Cost savings and avoidance from clinical interventions.Am J Health Syst Pharm. 1997;54:392-396. Phillips MS, Gayman JE, Todd MW.ASHP guidelines on medication-use evaluation.Am J Health Syst Pharm. 1996;53:1953-1955.

Online Sources: www.jointcommission.org www.qualityforum.org

Copyright 2011 American Society of Consultant Pharmacists