ASPIRE CLASS 1: Conceiving the Research Idea Sarah J. Billups, PharmD, BCPS, Clinical Pharmacy Specialist Samuel Johnson, PharmD, BCPS (AQ Cardiology), Clinical Pharmacy Specialist

Learning Objectives Class 1: Conceiving the Research Idea ASPIRE Class 1: Conceiving the Research Idea Write a research question that meets PICO & FINER criteria Formulate primary and secondary objectives Formulate study hypotheses and select outcome measures for each objective Use a well-written study question to survey primary literature Identify an efficient process for reviewing articles and managing references

Where Do Research Questions Come From?

Where Do Research Questions Come From? Clinical practice Literature Institutional and clinical problems Could be a problem you regularly encounter in practice, or a question that comes up in reading literature, or institutional issues or concerns, such as meeting quality objectives (JCACHO in the hospital, HEDIS in managed care)

Example Research Questions How effective is a clinical pharmacy service in managing patients with diabetes? Why do HMO patients take their prescriptions to outside (out of plan) pharmacies? What are the benefits of Medication Management? Why don’t patients pick up their new bisphosphonate prescriptions?

What Makes a Good Research Question? PICO Population Intervention Comparison Group Outcome Components of the question

What Makes a Good Research Question? FINER Feasibility Interesting Novel Ethical Relevant Quality of the question

Example Question Does a home blood pressure monitoring program improve hypertension control?

Quality/ Completeness Check: PICO Does a home blood pressure monitoring program improve hypertension control? Population Intervention Comparison Outcome Prob- Pop- who? Int- pharmacist-managed HBPM program Comparison- pts enrolled vs not enrolled ; pre and post NOT a good comparison here! Outcome- BP control; change in SBP

Quality/ Completeness Check: PICO Does a home blood pressure monitoring program improve hypertension control? Population—adult pts with a HTN diagnosis and uncontrolled HTN Intervention—Pharmacist-managed HBPM program Comparison—adult pts meeting inclusion criteria but not enrolled in program Outcome—achieving target BP Prob- Pop- who? Int- pharmacist-managed HBPM program Comparison- pts enrolled vs not enrolled ; pre and post NOT a good comparison here! Outcome- BP control; change in SBP

Revised Question Does a pharmacist-managed home blood pressure monitoring program increase the proportion of hypertensive patients with uncontrolled BP who achieve their target blood pressure compared to similar patients receiving usual care?

Why don’t patients pick up their new bisphosphonate prescriptions? Example Question #2 Why don’t patients pick up their new bisphosphonate prescriptions?

Quality/ Completeness Check: PICO Why don’t patients pick up their new bisphosphonate prescriptions? Population Intervention Comparison Outcome Prob- Pop-women only? Adults only? What’s a bisphosphonate? (oral vs parenteral) What’s a “new” Rx? What does “picked up” mean? Int-not for this question; could develop a service to address this problem, but that’s a later step Comparison-who to compare to? Outcome-list of reasons? Patient characteristics? Pt beliefs about bisphosphonates? About osteoporosis? Pt $ constraints?

Quality/ Completeness Check: PICO Why don’t patients pick up their new bisphosphonate prescriptions? Population—adult women who don’t purchase an oral bisphosphonate Rx within 90 days of its being written Intervention— N/A Comparison—patients who DO purchase their Rx… Outcome—questionnaire responses Prob- Pop-women only? Adults only? What’s a bisphosphonate? (oral vs parenteral) What’s a “new” Rx? What does “picked up” mean? Int-not for this question; could develop a service to address this problem, but that’s a later step Comparison-who to compare to? Outcome-list of reasons? Patient characteristics? Pt beliefs about bisphosphonates? About osteoporosis? Pt $ constraints?

Revised Question How do beliefs about osteoporosis and bisphosphonates differ between adult women with new prescriptions for oral bisphosphonates who do versus do not purchase their medication within 90 days of its being ordered?

Quality Check: FINER Feasibility Interesting Novel Ethical Relevant Feas—non-interventional, so Q is getting data– Pt identification? (Administrative) Characteristics? (Administrative) Beliefs? (Survey) Also—enough subjects? Technical expertise? Cost and duration? Scope? Interesting– real patient problem Novel– Confirms or refutes or extends previous findings; Provides new findings Ethical– Relevant– to scientific knowledge; to future research directions—could lead to designing a successful intervention

What does the ‘C’ stand for in PICO ? Knowledge Check What does the ‘C’ stand for in PICO ? Cohort Context Confounder Comparison Group Components of the question

What does the ‘C’ stand for in PICO ? Knowledge Check What does the ‘C’ stand for in PICO ? Cohort Context Confounder Comparison Group Components of the question

Elements of a Research Protocol Objectives Background Design Research Question Population Analytical Plan Procedures

Objectives, Hypotheses, and Outcomes What you want to learn Hypothesis What results do you expect? Outcome How you plan to measure it Specific

Study Objectives (Study Aims) What the study will achieve Guides thinking, study design, analysis, and reporting Serves as outline for organizing later sections Methods section should follow parallel sequence Can have multiple objectives; designate a primary and remainder as secondary or tertiary Not too many! Outlines what the study will achieve Limit number to keep your study focused

Study Objectives: Example Compare concerns about medication cost between patients with and without primary nonadherence (defined as those who did versus did not purchase a new bisphosphonate prescription within 90 days of its being written).

Study Hypothesis Definition: prediction of the relationship between one or more factors and the problem under study More specific than objectives and are amenable to explicit statistical evaluation Guides how to conduct the statistics as the type of data collected/analyzed should be clear

Study Hypothesis Most appropriate for intervention/evaluative studies Difficult for descriptive/exploratory studies At least 1 hypothesis for each objective can have more than 1 Simple, specific, and stated in advance Stated as null or alternative statistical analysis based on null hypothesis Not usually possible for descriptive studies

Example Objective: Compare concerns about prescription cost between patients with and without primary non-adherence.

Example Hypothesis: Alternative: Patients with primary non-adherence will have more concern about prescription costs than adherent patients Null: Patients with and without primary non-adherence will have the same level of concern about prescription costs

Study Outcome(s) This is the specific thing you are going to measure In this study, we are using a telephone questionnaire and asking patients to respond to the question “How concerned are you about the cost of this medication?” with “very, somewhat, a little, or not at all”

Example Outcome: The proportion of patients in each group who express that they are “very” or “somewhat” concerned about prescription cost in response to a telephone survey NOTE:

Objective, Hypothesis, and Outcome Example 2 Objective: To identify the incidence of bisphosphonate primary non-adherence over a 3 month period Hypothesis: Outcome: Among patients with a new oral bisphosphonate prescription written between August 1 and October 31, 2012, the percent who do not purchase it within 90 days

Knowledge Check Components of the question

Classify the following statement : Knowledge Check Classify the following statement : High school students given two samples of cola will express a preference for Pepsi over Coke. Study Objective Null Hypothesis Alternative Hypotheses Study Outcome Components of the question

Classify the following statement : Knowledge Check Classify the following statement : High school students given two samples of cola will express a preference for Pepsi over Coke. Study Objective Null Hypothesis Alternative Hypotheses Study Outcome Components of the question

Elements of a Research Protocol Background Population Design Objectives Procedures Analytical Plan Research Question

Researching Background: Goals Understand what is already known about the subject and where there are holes Learn how others have approached this problem Reveal limitations or holes in the existing literature

Building the Background Broad statement of topic Review relevant published literature Outline gaps in the literature and why these gaps are important End with research question/purpose statement What is known? What is not known? Why do I care?

General Search Strategies Tips to insure a high-quality, systematic search: Use at least two databases Check references of studies meeting inclusion criteria Check with content experts to make sure relevant studies are not missed Search for ‘gray’ literature Avoid limiting searches by date Come up with a process for reference management (manual or software assisted) Record search history Start with your PICO question(s) Establish preliminary search terms Establish inclusion and exclusion criteria

Free Resources for Reference Management PubMed: Register for a free NCBI Account EndNote Web Version: Register for free access (1 year) Manual management: Hey, whatever works!

PubMed Resources Pros Cons It’s free It’s easy to access Most people are familiar with it It doesn’t include gray literature Access to most full-texts requires you to use a PC with a KPCO IP address

EndNote Web Resource Pros Cons It’s free It enables you to maintain a comprehensive electronic reference list It’s widely accessible It’s only free for 1 year The interface is not that intuitive Not all functionality is available on KP PCs

Manual Reference Management Pros Cons It’s free ;) Not vulnerable to IT issues ;) It’s like retro, man

Once You Have References… Determine which should be included (relevant) Devise a scheme for routinely updating reference list (PubMed resources) Detail references in your protocol, posters, and manuscript

Assessing Quality of Studies Appropriate study design Application of appropriate statistical testing Identification of bias and conflicts of interest Meaningful synthesis of results Appropriate conclusions drawn Various published quality assessment tools are available (email me if you are interested)

Sample Evidence Summary Study N Design Inclusion criteria Intervention Comparator Outcomes Median follow-up Chacon, 2011 675 RCT >18 years KP member Normal Renal function Bloodletting Leeches Syncope 30 days

Sample Evidence Table More detailed than evidence summary May be used to fuel a SR and meta-analysis Screenshot example(s)

In summary… Start with a good PICO question Record your search history, consult with content experts Devise a systematic way to review and store references (and stick to it ;) Use free online resources to your advantage Recognize opportunities for ST and meta-analysis Evidence synthesis Development of guidelines or consensus statements

Class 1 Assignment Begin background literature review for your study Prepare a 5-10 min presentation for your small group session including draft versions of the following: Your research question (use FINER and PICO criteria) Primary and secondary objectives A hypothesis and study outcome(s) for each objective Please come prepared with the above items Kaiser Permanente Central Support Services