ASPIRE Workshop 2: Choosing Your Study Design and Population Hope everyone is doing well and that your research projects are progressing as you had expected! So, today’s sessions are primarily focused on coming up with your study design and entry criteria. Kerry Schwarz, Pharm D, MPH

Workshop 3 Assignment Give a 5-10 min presentation of the following to your small group: Study design and setting Study population inclusion and exclusion criteria Be prepared to discuss generalizability and validity of your selection criteria So, in your small group sessions….. Recap with everyone your revised study question/objectives to be sure everyone is on the same page. Probably good idea to share with your small groups some of the discussions you’re had with your site teams to share with your small groups rationale for the direction you’re taking your project. Then you will…… Small groups/mentors should focus on key elements in these areas mentioned here.

Study Designs: Recap May 22, 2019 | © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

To examine the association between glucocorticoid use and VTE Randomized, controlled trial Case series Case-control study Cross-sectional study Background: Excess endogenous cortisol has been linked to venous thromboembolism (VTE) risk, but whether this relationship applies to exogenous glucocorticoids remains uncertain Answer: C JAMA INTERNAL MEDICINE 2013;173:743-52. May 22, 2019 | © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.

To determine the impact of smoking on lung cancer rates Randomized, controlled trial Case-control study Cross-sectional study Cohort study Retrospective or prospective Answer: C Rates include time, so you would need to design this to be longitudinal Would you do this prospectively or retrospectively?

To describe sub-therapeutic linezolid concentrations in a patient with morbid obesity Randomized, controlled trial Cross-sectional study Case report Pre/Post study Answer: C

Randomized, controlled trial Cross-sectional study To determine the cardiovascular risk factor knowledge among patients with diabetes in a diabetes education program Randomized, controlled trial Cross-sectional study Retrospective, longitudinal cohort study Pre/Post study Answer: B

To determine the efficacy of combined teriparatide and denosumab with both agents alone on bone mineral density in women with osteoporosis Randomized, controlled trial Case-controlled study Cross-sectional study Cohort study Osteoporosis medications increase bone-mineral density (BMD) and lower but do not eliminate fracture risk. The combining of anabolic agents with bisphosphonates has not improved efficacy. We compared combined teriparatide and denosumab with both agents alone. Answer: A Discuss efficacy vs. effectiveness Are there any questions about any of this? Things you are still unclear about that would be beneficial for the large group to hear? Lancet 2013;382:50-56.

Study Question Among patients with Type 2 DM likely to benefit from statin therapy, will an intervention involving a letter, a pre-ordered statin prescription, and pharmacist counseling increase the proportion of patients on statins compared to no intervention?

PRIMARY Objective, Hypothesis, and Outcome Primary Objective: To evaluate whether the intervention will increase the proportion of patients with DM who purchase a statin compared to usual care Hypotheses: More patients in the intervention group will purchase a statin compared to usual care. Primary Outcome: % of patients who purchase a statin within 3 months of the receiving the intervention

Possible Study Designs Pre/Post study Randomized, controlled trial Cohort study Prospective or retrospective Quasi-experimental study Other study? Pre/post study: this is a very common method of assessment in pharmacy-practice-based studies as it is easy, fairly quick What are some problems with this design however? B. Randomized, controlled

Study Inclusion and Exclusion Criteria Inclusion Criteria Age between 40-80 years Diabetes Mellitus Type 2 Total cholesterol >135 mg/dL No statin purchases within prior year KPCO member Exclusion Criteria ALT > 60 or SCr >2.0 within past year Prior CPK >2x ULN within past 2 years Non-English reader No baseline cholesterol labs Receiving therapy with fibrates or cyclosporine within past 90 days Hospice/palliative care Writing techniques: do not “label pts” with their disease or condition. Pts have the disease but are not …. When writing these, no need to place something that is in the inclusion criteria also in exclusion criteria: Age, As you are working through these, you need to think about how you are going to “operationalize” these things. What do I mean by that? Additionally, you want to think about the balance b/w internal validity and external validity

Intervention Intervention will be A letter explaining: The benefits/risks of statins Information on the statin ordered for them How to pick-up the prescription When to come in for follow-up labs Who to call with questions/concerns Usual Care is the healthcare a patient normally would receive Orders for simvastatin 40 mg qd and appropriate labs will be entered for each pt in the intervention group F/u labs will be reviewed and triaged by clinical pharmacy specialist at each clinic Monthly reports of patients due for labs will be provided to CPS who will call patients to come for as needed.

Internal Validity External Validity Confounding Bias Discussion Internal Validity External Validity Confounding Bias A confounder is a third variable that can make it appear (sometimes incorrectly) that an observed exposure is associated with an outcome. In other words, a confounder is an unobserved exposure associated with the exposure of interest and is a potential cause of the outcome of interest. Confounders lead to bias that distorts the magnitude of the relationship between two factors of interest. Conditions for a Factor to be a Potential Confounder: Must be a risk factor for the outcome (disease) Must be associated with the exposure. Must not be an intermediate step in the causal path Should not be a surrogate for exposure Many types of bias have been discussed but can be reduced to two broad types of bias: Selection bias - Concern is that patients have different probability of being selected according to exposures or outcomes of interest Information bias - Collection of erroneous study data

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