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A GUIDE FORPHARMACISTSthird edition

Editors

Patrick M. Malone, PharmD, FASHP Karen L. Kier, PhD, MSc, RPh

Professor of Pharmacy Practice Professor of Clinical Pharmacy

Assistant Dean Director, Drug Information

The University of Findlay Director, NTPD Program

School of Pharmacy College of Pharmacy

Findlay, Ohio Ohio Northern University

Ada, Ohio

John E. Stanovich, RPh

Assistant Professor of Clinical Pharmacy

Assistant Dean

College of Pharmacy

Ohio Northern University

Ada, Ohio

McGraw-HillMedical Publishing Division

New York • Chicago • San Francisco • Lisbon • London • Madrid • Mexico City • MilanNew Delhi • San Juan • Seoul • Singapore • Sydney • Toronto

Contents

Contributors xixPreface xxiiiAcknowledgments xxvi

Chapter One . Introduction to the Concept of Medicat ion Information ... 1Mary Lea Gora-Harper and Ann B. Amerson

Introduction 1The Beginning 2The Evolution 5

Drug Information—From Centers to Practitioners/6 • Factors Influencing theEvolution of the Pharmacist's Role as a Medication Information Provider/8 •Educating for the Need/17

Opportunities in Specialty Practice 18Contract Drug Information Center (Fee-for-Service)/18 • Medical Informaticsin a Health System/19 • Health Maintenance Organizations (HMOs)/Pharmacy Benefit Management Organizations (PBMs)/Managed CareOrganizations/19 • Poison Control/20 • Pharmaceutical Industry/21 •Academia/22 • Scientific Writing and Medical Communication/22

Summary and Direction for the Future 23

Chapter Two. Modified Systematic Approach to Answering Questions 29Craig F. Kirkwood and Karen L. Kier

Modified Systematic Approach 30Requestor Demographics/31 • Background Questions/31 • UltimateQuestion/Categorization of Question/32 • Search Strategy/33 •Data Evaluation, Analysis, and Synthesis/33 • Formulation and Provision ofResponse/34 • Follow-Up, Follow-Through, and Documentation/35

Vi CONTENTS

Conclusion 35Study Questions 36

Chapter Three. Formulating Effective Responses andRecommendations: A Structured Approach 39

Karim Anton Calis and Amy Heck SheehanAccepting Responsibility and Eliminating Barriers 40Identifying the Genuine Need 40Formulating the Response 43

Building a Database and Assessing Critical Factors/43 • Analysis andSynthesis/46 • Responses and Recommendations/46 • Follow-Up/47

Case Study 1 47Case Study 2 49Case Study 3 52Case Study 4 55Conclusion 58Study Questions 58

Chapter Four. Drug Information Resources 61

Kelly M. Shields and Elaine LustIntroduction 61Tertiary Resources 62General Product Information 66

AHFS Drug Information/66 • Clinical Pharmacology/66 • DRUGDEX® InformationSystem/66 • Drug Facts and Comparisons/66 • Drug InformationHandbook/67 • Handbook of Clinical Drug Data/67 • Handbook ofNonprescription Drugs: An Interactive Approach to Self-Care/67 •Physicians' Desk Reference/67 • USPDI Volumes I, II, and 111/68 •USP Dictionary of USAN and International Drug Names/68

Adverse Effects 68Meyler's Side Effects of Drugs/68

Availability of Dosage Forms 69American Drug Index/69 • Red Book/69

Compounding 69Allen's Compounded Formulations/69 • Extemporaneous Formulations/69 •Merck Index/69 • Remington: The Science and Practice of Pharmacy/70 •A Practical Guide to Contemporary Pharmacy Practice/70 • USP/NF/70

CONTENTS VM

Dietary Supplements 70

Natural Medicine Comprehensive Database/70 • Natural TherapeuticsPocket Guide/71 • Review of Natural Products/71 • The Complete GermanCommission E-Monographs/71 • PDR for Herbal Medicines/71 •Professional's Handbook of Complementary and Alternative Medicine/72

Dosage Recommendations 72Drug Prescribing in Renal Failure/72

Drug Interactions 72Hansten and Horn's Drug Interaction Analysis and Management/72 •Drug Interaction Facts/72 • DRUG-REAX/73 • Evaluations of DrugInteractions/73 • Drug Therapy Monitoring System/73 •Stockley's Drug Interactions/73

Foreign Drug Identification 73

European Drug Index/73 • Index Nominum: International Drug Directory/74 •Martindale: The Complete Drug Reference/74

Geriatric Dosage Recommendations 74Geriatric Dosage Handbook/74 • The Merck Manual of Geriatrics/74

Identification of Product 75Ident-a-Drug/75 • IDENTIDEXV75

Incompatibility and Stability 75Handbook on Injectable Drugs/75 • King Guide to Parenteral Admixtures/75 •Trissel's Stability of Compounded Formulations/76 • Trissel's™ 2 ClinicalPharmaceutics Database/76

Pediatric Dosage Recommendations 76The Harriet Lane Handbook/76 • Neofax/76 • Pediatric Dosage Handbook/76

Pharmacokinetics 77Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring/77 •

Basic Clinical Pharmacokinetics/77 • Clinical Pharmacokinetics:

Concepts and Applications/77

Pharmacology 77Goodman & Gilman's: The Pharmacological Basis of Therapeutics/77 •Basic & Clinical Pharmacology/77 • Principles of Pharmacology/78

Pharmacy Law 78Guide to Federal Pharmacy Law/78 • Pharmacy Practice and the Law/78

Teratogenicity/Lactation 78Drugs in Pregnancy and Lactation/78 • Medications and Mother's Milk:A Manual of Lactational Pharmacology/79 • REPRORISK®/79

viii CONTENTS

Therapy Evaluation/Drug of Choice 79Applied Therapeutics: The Clinical Use of Drugs/79 • Cecil Textbook ofMedicine/79 • Harrison's Principles of Internal Medicine/79 • The MerckManual of Diagnosis and Therapy/80 • Pharmacotherapy: A PathophysiologicApproach/80 • Textbook of Therapeutics/80

Toxicology 80Casarett & Doull's Toxicology: The Basic Science of Poisons/80 • Ellenhorn'sMedical Toxicology: Diagnosis and Treatment of Human Poisoning/80 •Goldfrank's Toxicologic Emergencies/'81 • POISINDEX®/81

Veterinary Medicine 81Compendium of Veterinary Products (CVP)/81 • Food and Drug Administration/Center for Veterinary Medicine Home Page/81 • The 5-Minute Veterinary Consultant:Canine and Feline/82 • Textbook of Veterinary Internal Medicine: Diseases of the Dogand Cat/82 • Veterinary Drug Handbook/82

References for PDA 83Secondary Literature 83

Anti-Infectives Today/86 • Biologic Abstracts/Biosis Previews/86 • CancerToday/86 • Cancerlit/86 • CINAHL®/87 • The Cochrane Database ofSystematic Reviews/87 • Current Contents/87 • EMBASE/87 • Google™Scholar/87 • Inpharma Weekly/88 • International PharmaceuticalAbstracts (IPA)/88 • Iowa Drug Information System/88 • JournalWatch/88 • LexisNexis/88 • MEDLINF®/89 • Paediatrics Today/89 •PharmacoEconomics and Outcomes News Weekly/89 • Reactions Weekly/89

Primary Literature 89Obtaining the Primary Literature 90Internet Resources 90Alternative Information Sources 92Consumer Health Information 93Conclusion 94Study Questions 95

Chapter Five. Electronic Information Management 103

Patrick M. Malone

Introduction 103Technology—The First Step 104Information via the Internet 106

The Present/106 • The Future/129

CONTENTS iX

Acknowledgment 131

Study Questions 131

Chapter Six. Controlled Clinical Trial Evaluation 139

Michael G. Kendrach and Maisha Kelly Freeman

Biomedical/Pharmacy Literature 141

Approach to Evaluating Research Studies (True Experiments) 145

Journal, Peer-Review, and Investigators 145

Clinical Trial Title 148

Abstract 148

Introduction 149

Methods 150Study Design/151 • Patient Inclusion/Exclusion Criteria/152 •Intervention and Control Groups/156 • Institutional Review Board(IRB)/Subject Consent/159 • Blinding/159 • Randomization/161 •Endpoints/163 • Follow-Up Schedule/Data Collection/Compliance/165 •Sample Size/166 • Statistical Analysis/168 • Types I and II Errors/PowerAnalysis/173

Results 176Subject Demographics/176 • Subject Dropouts/Compliance/177 • Endpointsand Safety/178 • Subgroup Analysis/180 • Ancillary versus AdjunctiveTherapies/182

Discussion/Conclusion 183

Clinical Trial Result Interpretation 185Statistical Significance versus Clinical Difference/185 • Assessing ClinicalDifference/186 • Confidence Intervals/188 • Interpreting Risks andNumbers-Needed-to-Treat/190 • "No Difference" Does Not Indicate"Equivalency"/193 • Assessing the Clinical Meaningfulness of the Results/193 •Standard of Care/194

Bibliography/References 195

Acknowledgments 195

Funding 196

Commentaries/Clinical Trial Critiques 197

Letters-to-the-Editor/199

Conclusion 199

Study Questions 200

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Chapter Seven. Literature Evaluation II: Beyond the Basics 213Karen P. Norris, Carrie J. Johnson, H. Glenn Anderson, Jr., Patrick J. Bryant,Elizabeth A. Poole, Cydney E. McQueen, and Linda R. Young

Introduction 214Experimental Study Design 215

True Experiments—Beyond the Controlled Clinical Trial/216 • Stability Studies/In Vitro Studies/218 • Bioequivalence Studies/219 • Programmatic Research/222

Observational Study Design 222Cohort Studies/223 • Case-Control Studies/226 • Cross-SectionalStudies/231 • Case Studies, Case Reports, and Case Series/232

Survey Research 232Postmarketing Surveillance Studies 237Pulling It All Together: Organizing and Ranking Studies 238Review Articles 239

Narrative (Nonsystematic) Reviews/240 • Systematic Review—Qualitative/241 • Systematic Reviews—Quantitative (Meta-Analyses)/243

Practice Guidelines 246Health Outcomes Research 247

Quality-of-Life Measures/247

Dietary Supplement Medical Literature 252Standardization/252 • International Trials/253 • Duration/253 • TrialSize/253 • Lack of Evidence/254 • Other Special Considerations/254

Conclusion 254Study Questions 255Acknowledgment 256

Chapter Eight. Pharmacoeconomics 261James P. Wilson and Karen L Rascati

Pharmacoeconomics—What Is It and Why Do It? 262Relationship of Pharmacoeconomics to Outcomes Research 262Models of Pharmacoeconomic Analysis 263Assessment of Costs 263

Types of Costs/263 • Timing Adjustments for Costs/264Assessment of Outcomes 265

Cost-Minimization Analysis/265 • Cost-Benefit Analysis/266 •Cost-Effectiveness Analysis/269 • Cost-Utility Analysis/270

CONTENTS Xi

Performing an Economic Analysis 273Step 1: Define the Problem/274 • Step 2: Determine the Study's Perspective/274 •Step 3: Determine Specific Treatment Alternatives and Outcomes/274 •

Step 4: Select the Appropriate Pharmacoeconomic Method or Model/275 •Step 5: Measure Inputs and Outcomes/275 • Step 6: Identify the ResourcesNecessary to Conduct the Analysis/275 • Step 7: Establish the Probabilitiesfor the Outcomes of the Treatment Alternatives/276 • Step 8: Construct aDecision Tree/276 • Step 9: Conduct a Sensitivity Analysis/276 • Step 10:Present the Results/277

What Is Decision Analysis? 277

Steps in Decision Analysis/277

Steps in Reviewing Published Literature 281

Evaluation/283

Selected Pharmacoeconomics Websites 284

Conclusion 284

Study Questions 285

Chapter Nine. Evidence-Based Clinical Practice Guidelines 289

Kevin G. Moores

Introduction 289

Evidence-Based Practice and Clinical Practice Guidelines 291Guideline Development Methods 294

Select a Topic for Guideline Development/298 • Recruit AppropriateMultidisciplinary Membership for a Panel to be Involved in Development of theGuideline/299 • Define the Clinical Questions to be Addressed/302 • Determinethe Criteria for Evidence/303 • Conduct a Systematic Search for the QualijyingEvidence/304 • Perform a Systematic Evaluation and Grading of Hie Evidence/305 •Prepare a Synthesis of the Evidence/306 • Agree on Procedures for a ConsensusProcess, or Other Procedures for Making Recommendations, in the Absence ofHigher Levels of Evidence for Decision Making/308 • Formulate and GradeRecommendations Based on the Grade of Evidence and Balance of Benefits, Harms,and Costs of Treatment Options/308 • Draft the Guideline Document/309 •Conduct Peer-Review andPUot Testing of the Guideline/311 • Revise the Guidelineas Appropriate/312 • Create Tools for Implementation of the Guideline/312 •Establish a Plan for Follow-Up and Periodic Updating of the Guideline/313

Interpretation of Guideline Recommendations 313

Guideline Evaluation Tools 318

Xii CONTENTS

Implementation of Clinical Practice Guidelines 321Sources of Clinical Practice Guidelines 325

Conclusion 330Study Questions for Evidence-Based Clinical Practice Guidelines 330

Chapter Ten. Clinical Application of Statistical Analysis 339Karen L. Kier

Basic Concepts 340Populations and Samples/340 • Variables and Data/341

Descriptive and Inferential Statistic 343Descriptive Statistics/343 • Measures of Central Tendency/344 • Measures ofVariability/345 • Measures of Shape/346 • Ratios, Proportions, and Rates/347 •Incidence and Prevalence/347 • Relative Risk and Odds Ratio/348 •Sensitivity, Specificity, and Predictive Values/349 • Distributions/350 •

Statistical Inference 353Central Limit Theorem/353 • Parametric versus Nonparametric Testing/354 •Hypothesis Testing/355 • Errors/355 • Significance/356 • Statistical Tests/357• Comparing Two Groups/358 • Comparing More Than Two Groups/360• Describing the Relationship Between Two or More Variables/362 • OtherNonparametric Tests/367

Other Methods of Inference for Categorical Data 368Other Nonparametric Tests 369

Survival Analysis/369 • Multivariate Analysis/370 • Other Types of StudyDesign with Statistical Analysis/372

Conclusion 373Study Questions 373

Chapter Eleven. Professional Writing 375Patrick M. Malone

Introduction 375Steps in Writing 376

Preparing to Write/377 • General Rules of Writing/381 • Specific DocumentSections/384 • Submission of the Document/389 • Revision/390 • GalleyProofs/390

Referees 391

Specific Documents 391Newsletters and Websites/391 • Presentations/398

Conclusion *tr?

CONTENTS Xiii

Chapter Twelve. Legal Aspects of Drug Information Practice 411Martha M. Rumore

Tort Law 412

Incomplete Information/415 • Inappropriate Quality Information/418 •

Inappropriate Analysis/Dissemination of Information/420

Defenses to Negligence and Malpractice Protection 421Defenses for Individuals/422 • Defenses for Employers/423 • Protecting

Against Malpractice/424

Labeling and Advertising 426Direct-to-Consumer Drug Information and Erosion of the Learned

Intermediary Rule/427 • Doctrine of Drug Overpromotion/429 • Off Label

Use and Informed Consent/430

Liability Concerns for Internet Information 432Quality of Information/432 • Telemedicine and Cybermedicine/433 • Fraudand Abuse/435

Intellectual Property Rights 436

Copyright/436 • Digital Millennium Copyright Act/442

Privacy 443Health Insurance Portability Act of 1996/443 • Communication Privacy/445

Industry Support for Educational Activities 446

Guidelines and Guidance/447 • Relationship to Antikickback Statute/449

Conclusion 450

Study Questions 451

Chapter Thirteen. Ethical Aspects of Drug Information Practice 459

Linda K. Ohri

What Is Ethics and What Is Not 459

Ethical Dilemmas in Pharmacy Practice 460

Basics of Ethics Analysis 462Definitions Used in the Field of Ethics/462 • Overview of a Suggested

Process of Analysis to be Used When an Ethical Dilemma Arises/463 •An Annotated Listing of Rules and Principles (Action-Guides) Applied in

Medical Ethics Inquiry/468

Demonstration of the Process for Analyzing Ethical Dilemmas 470

Demonstration of Case Analysis/470

Resources for Use by Pharmacists Seeking to Learn More About

Medical Ethics 476

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Structures That Support Ethical Decision-Making 477

Summary 479Study Questions 479

Chapter Fourteen. Pharmacy and Therapeutics Committee 483Patrick M. Malone, Mark A. Malesker, PaulJ. Nelson, and Nancy L Fagan

Introduction 483Organizational Background 485

Pharmacy Benefit Management P&T Committee Origin/488 • Pharmacy Supportof theP&T Committee/490 • Ad Hoc Committees/'495 • P&T CommitteeMeeting/496 • Formulary Management/498 • Policies and Procedures/510

Clinical Guidelines 513Standard Order Set Development 513Credentialing and Privileges 514Quality Improvement within the P&T Committee—Internal Audit 515

Medication Quality Assurance/515 • Adverse Drug Reactions/516 •Medication Error Incidents/516 • Illegible Handwriting, Transcription, andAbbreviations/516 • Timeliness/517 • Counterfeit Drug Products/517 •Safety Alert/518 • Product Shortages/519

Communication within an Organization 519Investigational Review Board Actions/519 • Cost, Budget, andForecasting/520 • Liaison with Other Elements of theOrganization/520

Conclusion 521Acknowledgment 522Study Questions 522

Chapter Fifteen. Drug Evaluation Monographs 533Patrick M. Malone, Mark A. Malesker, Nancy L Fagan, PaulJ. Nelsonand Linda K. Ohri

Introduction 533Summary Page/536 • Body of the Monograph/545

Conclusion 553

Chapter Sixteen. Quality Improvement and the Medication Use Process 557Mark A. Ninno and Sharon Davis Ninno

Quality Improvement 557Defining Quality/558 • Quality in Healthcare/562 • Quality and theJCAHO/565 • Standards/566 • Patient-Focused Care/567 •

CONTENTS XV

Organization-Focused Functions/567 • Structures with Functions/568 •Medication Management Standards/568 • Quality and Managed

Care/571

Drug Regimen Review and Drug Use Review 574Medication Use Evaluation/575 • The Medication Use Process/575 •

Medication Use Evaluation and the JCAHO/576

Quality in Drug Information 591

Conclusion 592

Study Questions 593

Chapter Seventeen. Medication Misadventures: Adverse Drug

Reactions and Medication Errors 599Philip J. Gregory

Adverse Drug Reactions 601Definitions/602 • Causality and Probability of Adverse Drug Reactions/603 •Classification/605 • Mechanism of Adverse Drug Reactions/605 • Reporting/606 •The FDA Reporting/606 • Dietary Supplements/608 • TheJCAHO and the ASHPGuidelines/609 • Implementing a Program/609 • Technology/611

Medication Errors 612Definitions/612 • Classification/614 • Error Type/614 • Outcome orSeverity/616 • Subclassifications/617 » Psychology of Medication Errors:Why Do Errors Occur?/617 • Medication Error Reporting/620 •Institutional Reporting/622 • National Reporting/622 • ErrorPrevention/624 • Practitioner Strategies/625 • Health SystemStrategies/626 • National Priority/628

Conclusion 630

Study Questions 631

Chapter Eighteen. Investigational Drugs 635

Bambi Grilley

Definitions 636

History of Drug Development Regulation in the United States 638

The Drug Approval Process 641

The Institutional Review Board 650

The Orphan Drug Act 651

Role of the Pharmacist 652

Conclusion 658

Study Questions 659