The Role of the Nurse in Drug Research 1.

THE FOUR BASIC ETHICAL PRINCIPLES THAT ARE RELEVANT TO RESEARCH INVOLVING HUMAN SUBJECTS: 1. RESPECT FOR PERSONS 2. BENEFICENCE 3. JUSTICE 4. TRUTH TELLING 2. BASIC ETHICAL PRINCIPLES RESPECT FOR PERSONS: CLIENTS: SHOULD BE TREATED AS AN INDEPENDENT CAPABLE TO MAKE DECISIONS IN THEIR OWN BEST INTEREST. FOR THOSE WHO CAN NOT ARE ENTITLED TO PROTECTION. NURSE CAN DETERMINE THIS WITH CONSISTENT REASSESSMENT OF CLIENTS COGNITIVE STATE. CLIENTS CHOICE MUST BE HONORED, NURSE MUST RECOGNIZE IF A CLIENT NEEDS PROTECTION. 3. THE RIGHT TO SELF-DETERMINATION AUTONOMY 4. PATIENT RIGHTS RESPECT THE CLIENTS' RIGHT TO MAKE DECISIONS ABOUT THEMSELVES, EVEN IF THE DECISION IS NOT WHAT THE PERSONNEL WANTED OR THOUGHT WAS BEST FOR THE CLIENT. CLIENT CAN REFUSE ANY AND ALL TREATMENTS **EXCEPT WHEN THE DECISION POSES A THREAT TO OTHERS. RIGHT TO REFUSE TO PARTICIPATE IN A RESEARCH STUDY AND MAY WITHDRAW FROM A STUDY AT ANY TIME WITHOUT PENALTY OF ANY KIND. 5. BASIC ETHICAL PRINCIPLES BENEFICENCE: BENEFICENCE IS THE DUTY TO NOT HARM OTHERS, TO MAXIMIZE POSSIBLE BENEFITS, AND TO MINIMIZE POSSIBLE HARM THAT MIGHT OCCUR IN RESEARCH. CANT TELL IF ITS BENEFICIAL UNLESS TESTED AND CLIENT HAS BEEN EXPOSED TO RISKS, BUT: CENTRAL QUESTION IS - WHO MAKES THIS DECISION, CLIENT OR THOSE CARING FOR THE CLIENT.

6. BASIC ETHICAL PRINCIPLES JUSTICE: REQUIRES THAT ALL PEOPLE BE TREATED FAIRLY. EXPANSIONEQUAL ACCESS TO HEALTH CARE FOR ALL. LIMITED - WHEN IT INTERFERES WITH OTHERS RIGHTS. JUSTICE IN CLINICAL TRIALS: SOCIAL BENEFITS AND BURDENS CAN BE ALLOCATED OBJECTIVELY AND THOSE WITH EQUIVALENT CIRCUMSTANCES SHOULD BE TREATED EQUALLY. 7. VERACITY MEANS TRUTH TELLING; THE WHOLE TRUTH EVEN IF ITS BAD NEWS. THE CLIENT HAS THE RIGHT TO KNOW THE WHOLE TRUTH NO MATTER WHAT. 8. INFORMED CONSENT PATIENT HAS THE RIGHT TO BE INFORMED, PARTICIPATION IS VOLUNTARY WITHOUT COERCION, IF NURSE THINK A PARTICIPANT IS BEING COERCED THEY ARE OBLIGATED TO INFORM THE NAME ON THE INFORMED CONSENT. 9. INFORMED CONSENT HAS DIMENSIONS BEYOND PROTECTION BEYOND CLIENTS CHOICE AND INCLUDES: 1. PROMOTION OF INDIVIDUAL AUTONOMY 2. PROTECTION OF CLIENTS AND SUBJECTS FROM HARM 3. AVOIDANCE OF FRAUD AND DURESS IN HEALTH CARE 4. ENCOURAGEMENT FOR PROFESSIONALS TO BE THOROUGH AND CLEAR IN COMMUNICATING INFORMATION 5. PROMOTION OF EDUCATED DECISION MAKING AMONG CLIENT 6. PROMOTION OF SELF DETERMINATION OF THE CLIENT 10. IT IS THE ROLE OF THE HEALTH CARE PROVIDERS, NOT ______ TO EXPLAIN THE STUDY TO THE CLIENT THE NURSE 11. THE NURSES ROLE IS TO: PROTECT THE CLIENT FROM ANY HARM,MUST BE KNOWLEDGEABLE ABOUT ALL ASPECTS OF THE DRUG STUDY, INCLUDING ALL INCLUSIONS AND EXCLUSION CRITERIA FOR PARTICIPANTS.

12. RISK TO BENEFIT RATIO COMPLEX PROBLEM FACED BY RESEARCHER. ALL POSSIBLE CONSEQUENCES OF CLINICAL STUDY MUST BE ANALYZED AND BALANCED WITH THE INHERENT RISKS AND ANTICIPATED BENEFITS. PHYSICAL, PSYCHOLOGICAL, AND SOCIAL RISKS MUST BE IDENTIFIED AND WEIGHED AGAINST THE BENEFITS. "RISK TO SUBJECTS ARE REASONABLE IN RELATION TO ANTICIPATED BENEFITS, IF ANY, TO SUBJECTS" NO MATTER HOW NOBLE THE INTENTIONS, THE CALCULATION OF RISKS AND BENEFITS BY THE RESEARCHER CANNOT BE TOTALLY ACCURATE OR COMPREHENSIVE. VARYING AMOUNTS OF TIME ARE REQUIRED FOR THE PROCESS OF IDENTIFYING A POTENTIALLY USEFUL CHEMICAL, AND HAVING IT BECOME AVAILABLE TO THE GENERAL POPULATION. 13. INFORMED CONSENT CHECKLIST 1. PARTICIPATES VOLUNTARILY 2. IDENTIFIES RELATED DRUG, TREATMENTS, AND TECHNIQUES 3. DESCRIBES BENEFITS AND RISKS 4. DESCRIBES OTHER FORMS OF TREATMENT AVAILABLE 5. DESCRIBES LABORATORY TESTS TO MONITOR CLIENT'S REACTIONS 6. IDENTIFIES EXTENT OF CONFIDENTIALITY OF RESULTS 7. DESCRIBES AVAILABILITY OF EMERGENCY TREATMENT FOR ILLNESS/INJURY, IF ANY 8. STATES COMPENSATION FOR STUDY-RELATED INJURY, IF ANY 9. STATES COMPENSATION FOR PARTICIPATION, IF ANY 10. WRITES CONSENT CLEARLY AND UNDERSTANDS EASILY AT THE TENTH GRADE READING LEVEL 11. PROVIDES NAME AND TELEPHONE NUMBER OF CONTACT PERSON FOR CLIENT QUESTIONS AND CONCERNS. 14. EXAMPLE OF INCLUSION CRITERIA FOR A HYPOTHETIC PROTOCOL FOR AN EXPERIMENTAL DIURETIC MEDICATION 1. MEN AND WOMEN BETWEEN THE AGES OF 18 AND 65 YEARS 2. WEIGHT BETWEEN 50 AND 100 KG 3. SUBJECTS RECEIVE CARDIAC MEDICATIONS ONLY IF DOSE HAS BEEN STABLE FOR PAST 3 MONTHS 4. SUBJECTS ON SODIUM-RESTRICTED DIET 15. EXAMPLE OF EXCLUSION CRITERIA FOR A HYPOTHETIC PROTOCOL FOR AN EXPERIMENTAL DIURETIC MEDICATION

1. PREGNANT OR NURSING WOMEN 2. ALL WOMEN OF CHILDBEARING AGE WHO DO NOT RESPONSIBLY USE ORAL CONTRACEPTIVES 3. PERSONS WITH SEVERE DAMAGE OR DISEASE OF CARDIAC, HEPATIC, RENAL, NEUROLOGIC, OR MUSCULOSKELETAL SYSTEM. 4. CLINICALLY SIGNIFICANT LABORATORY VALUES 16. GOOD CLINICAL PRACTICE (GCP): CONSOLIDATED GUIDELINES INTERNATIONAL ETHICAL AND SCIENTIFIC STANDARDS, IS THE FOUNDATION FOR CLINICAL TRIALS. 17. BASIC SEQUENCE OF NEW DRUG DEVELOPMENT 1. IDENTIFICATION OF POTENTIALLY CLINICALLY USEFUL CHEMICAL ENTITY. 2. PRECLINICAL TESTING 3. STUDY DESIGNS 4. HUMAN CLINICAL EXPERIMENTATION: - PHASE I - PHASE II - PHASE III AND IV 18. PRECLINCAL TESTING: VITRO AND VIVO SYSTEM. VITRO- CONDUCTED IN A TEST TUBE OR OTHER LABORATORY EQUIPMENT. VIVO- CONDUCTED WITH LIVING ORGANISMS; FOLLOWED BY TOXICITY SCREENING TO IDENTIFY: 1. ABNORMAL CHANGES RELATED TO DRUG ADMINISTRATION. 2. PARAMETERS OF SAFE THERAPEUTIC DOSE. 19. CONTROL AND EXPERIMENTAL GROUPS ARE COMPARED EXPERIMENTAL GROUP - GETS EXPERIMENTAL INTERVENTIONS AND TREATMENT. CONTROL GROUP - DOES NOT GET EXPERIMENTAL INTERVENTIONS AND TREATMENT; PROVIDES A BASELINE AGAINST WHICH TO MEASURE THE EFFECTS OF THE TREATMENT. BEFORE HUMAN STUDIES, AN ASSESSMENT IS MADE OF THE SERIOUSNESS OF THE DISEASE TO BE TREATED USING THE DRUG IN RELATION TO THE DRUGS TOXICITY. 20. HUMAN CLINICAL EXPERIMENTATION

OUT OF 5000 TO 10000 POSSIBLE NEW DRUGS, ONLY ABOUT 5 ARE ENTERED INTO CLINICAL TRIALS. TAKES AVERAGE OF 9 TO 12 YEARS. 21. FDA MODERNIZATION ACT OF 1997 INCREASED THE MINIMUM AGE FOR SUBJECTS OF HUMAN CLINICAL EXPERIMENTATION. ACT ADVOCATES FOR CHILDREN AND APPROPRIATE TESTING FOR DRUGS TO BE USED BY THE PEDIATRIC POPULATION. 22. PHASE I TRIALS DESIGNED TO ASSESS SAFETY. TO DETERMINE HUMAN DOSAGE RANGE BASED ON RESPONSE IN HEALTHY HUMAN SUBJECTS AND TO IDENTIFY PHARMACOKINETICS. 23. PHASE II TRIALS DEMONSTRATE THE SAFETY AND EFFICACY OF THE DRUG IN SUBJECTS (N=100) WHO HAVE THE DISEASE THE DRUG IS DESIGNED TO TREAT. PHASE II STARTS ONLY WHEN SAFETY DATA IS GENERATED AND CLEARLY DOCUMENTED. 24. PHASE III AND IV TRIALS III- LARGE NUMBERS OF SUBJECTS WITH THE DISEASE INTENDED FOR TREATMENT. III & IV- DEMONSTRATE SAFETY AND EFFICACY OF DRUG FOR A WIDE CLIENT POPULATION, INCLUDE LONG TERM DATA IF CHRONIC REGIMEN IS UNDER CONSIDERATION. IV- EXAMINE POTENTIAL NEW INDICATIONS FOR APPROVED DRUGS. 25. TRIALS TO FDA SPONSOR SUBMITS ALL RELEVANT AND ANALYZED DATA IN NEW DRUG APPLICATION (NDA) TO FDA. IN TIME FDA DECIDES APPROVAL, REJECTION, RECOMMENDED WITHDRAWL OR RE-SUBMISSION. AFTER NDA RESEARCH HAS BEEN APPROVED, PHASE IV ADDRESSES LONGTERM USE OF THE DRUG. 26. PRESCRIPTION DRUG USER FEE ACT PASSED BY CONGRESS IN 1992; PROVIDED THE FDA WITH FUNDS TO EXPEDITE THE REVIEW PROCESS. AS A RESULT, AVERAGE DRUG APPROVAL TIME HAS DECREASED FROM 30 MONTHS TO 12 MONTHS.

27. STUDY DESIGNS EXPERIMENTAL DESIGNS USES DIFFERENT GROUPS OF SUBJECTS. THEY ASSIGN SUBJECTS RANDOMLY TO TREATMENT OR CONTROL GROUPS, THEY DO NOT DIFFER IN TERMS OF BASELINE CHARACTERISTICS OR DEMOGRAPHICS. 28. quasi-experimental design: THIS DESIGN IS A COMPARISON OF (IV) DEVICE PATENCY OF CLIENTS WHO RECEIVE HEPARIN FLUSHES AND THOSE WHO RECEIVED SALINE FLUSHES. NON-MATCHED COMPARISON GROUP BUT NO RANDOM ASSIGNMENT TO A TREATMENT GROUP. 29. RESEARCHER DESIGNS A STUDY TO SHOW: THE EFFECTS OF THE INDEPENDENT VARIABLE (THE DRUG) ON THE DEPENDENT VARIABLES (CLINICAL RESPONSES OR REACTIONS). THEY ARE SPECIFIC: AGE, SEX, WEIGHT, DISEASE AND ITS STATE OF SEVERITY, DIET, AND THE SUBJECTS SOCIAL ENVIRONMENT. 30. CONTROLLED TREATMENT GROUPS CAN RECIEVE NO DRUG INSTEAD A DIFFERENT DRUG CALLED WHAT IS GIVEN? A PLACEBO (PHARMACOLOGICALLY INERT SUBSTANCE); THE SAME DRUG WITH A DIFFERENT DOSE, ROUTE, OR FREQUENCY OF ADMINISTRATION. 31. A CONTROL GROUP RECEIVING A DIFFERENT DRUG IS CALLED A _______________? ACTIVE CONTROL 32. A CROSSOVER DESIGN USES EACH SUBJECT IN SEVERAL DIFFERENT SITUATIONS. THE EXPERIMENTAL GROUP RECEIVES THE DRUG - CONTROL GROUP RECEIVES AN ALTERNATIVE FORM OF TREATMENT OR NO TREATMENT. BOTH GROUPS RECEIVE NO THERAPY. EXPERIMENTAL GROUP RECEIVES THE CONTROL FORM OF THERAPY AND CONTROL GROUP RECEIVES THE DRUG. SUBJECT SERVES AS HIS OR HER OWN CONTROL. 33. PROBABILITY SAMPLING

STATISTICAL METHOD; SUBJECTS ARE RANDOMLY SELECTED FROM THE ENTIRE POPULATION, USED TO PROVIDE RELATIVE CONFIDENCE IN THE GENERALIZATION OF FINDINGS. 34. MATCHED-PAIR DESIGN RESEARCHER IDENTIFIES SEVERAL VARIABLES THAT MAY INFLUENCE THE OUTCOME SUCH AS AGE, WEIGHT, OR FAMILY HISTORY. SUBJECTS ARE MATCHED FOR THESE VARIABLES. ONE PAIR IS RANDOMLY ASSIGNED TO THE EXPERIMENTAL GROUP AND THE OTHER TO THE CONTROL GROUP. 35. DOUBLE BLIND TECHNIQUES POWERFUL TOOL WHEREIN NEITHER THE HEALTH CARE PROVIDER NOR THE SUBJECT KNOWS WHETHER THE SUBJECT IS RECEIVING THE EXPERIMENTAL OR CONTROL FORM OF THERAPY. 36. TRIPLE-BLIND STUDY RESEARCHER OTHER THEN PRESCRIBING HEALTH CARE PROVIDER COLLECTS DATA AND IS UNAWARE OF THE SUBJECTS TREATMENT GROUP. 37. SING BLIND STUDY ONLY SUBJECTS ARE UNAWARE OF WHICH GROUP TO WHICH THEY ARE ASSIGNED. 38. OPEN LABEL STUDY ALL PARTIES KNOW TREATMENT GROUP ASSIGNMENT. 39. PREFERRED TECHNIQUES FOR DRUG RESEARCH DOUBLE AND TRIPLE BLIND; BECAUSE THOSE INVOLVED IN THE STUDY ARE NOT AWARE OF THE SUBJECTS TREATMENT GROUP, THEREBY REMOVING A SOURCE OF BIAS. 40. NURSE'S ROLE MUST CONSIDER THEIR OWN THOUGHTS, FEELINGS AND BELIEFS ABOUT CLINICAL TRIALS. NURSE IS ADVOCATE BETWEEN CLIENT, HEALTH CARE PROVIDER, AND RESEARCH. RESPONSIBLE FOR SPECIFIC PROTOCOL. COMMUNICATION IS ESSENTIAL IN NURSES ROLE. ASKING QUESTIONS ABOUT INFORMED CONSENT AND RISK-TO-

BENEFIT RATIO IS ESSENTIAL. AWARENESS OF CHANGE, PREDICTION OF INCREASED RISK, CRITICAL TO ASSESSMENT PHASE ARE THE RECRUITMENT AND ASSESSMENT OF STUDY SUBJECTS; UNDERSTANDING PROTOCOL, INCLUSION AND EXCLUSION CRITERIA FOR SUBJECTS. COMMUNICATION WITH PROVIDERS AS WELL. INPUT IS IMPORTANT IN BUDGET NEGOTIATION, HELP STAFF EDUCATION PROTOCOL. AND HELP WITH FAMILY QUESTIONS ARISE. 41. PROTOCOL-BASED NURSING IMPLECATIONS INCLUDE COMPREHENSIVE SCREENING OF SUBJECT AND MONITORING PARAMETERS PER PROTOCOL WITH RELEVANT AND TIMELY COMMUNICATION WITH THE ENTIRE HEALTH CARE TEAM. DOCUMENTATION ON ALL PREDETERMINED COMPONENTS THROUGHOUT THE CLINICAL TRIAL IS MANDATORY, INCLUDING INPUT FROM STUDY SUBJECTS. DURING EVALUATION PHASE, ROLE IS EXAMINING THE RESEARCH STATEMENT OR QUESTION.