Writing Research Hypotheses and Specific Aims

Transcription

1 Writing Research Hypotheses and Specific Aims Cynthia Carnes, PharmD, PhD Resident Research Program July 20,2010 Define the research question Spend enough time to develop a good question READ, READ, READ A thorough literature review will help identify a high quality question Look for knowledge gaps or areas of controversy. Are you interested/excited/convinced about your idea? Research questions Purpose is to identify the area of study. Refine the scope of the question (avoid the temptation to go TOO BIG). Examples of too big: Does a better diet improve health? Do pharmacists improve patient care? 1

2 Once you have a question, what s next? What is the state of the field? Is there available information you can use to identify the next step? Is more information needed to clearly identify the best way forward? Study hypothesis vs. Study Purpose Every study has a purpose, not every study has a hypothesis Every study does not require a hypothesis Studies with a purpose May be observational, exploratory or descriptive Allow for a first look May be hypothesis generating 2

3 Non-hypothesis driven research: Example The effect of any antidiabetic therapy on cardiovascular outcomes is particularly important, because more than 65% of deaths in patients with diabetes are from cardiovascular causes We performed a meta-analysis of trials comparing rosiglitazone with placebo or active comparators to assess the effect of this agent on cardiovascular outcomes. Source: Nissen and Wolski, NEJM 2007; 356: compared with placebo or with other antidiabetic regimens, treatment with rosiglitazone was associated with a significant increase in the risk of myocardial infarction Did this study determine cause and effect? How does the question lead to a hypothesis? This is where you begin to really narrow your question. A solid hypothesis: Makes predictions about relationships between variables (cause and effect) Should address at least a part of the research question Is well-grounded in existing literature and knowledge 3

4 Writing your Hypothesis A hypothesis is a tentative statement that proposes a possible explanation to some phenomenon or event. A good hypothesis will: Have a strong rationale and address all or a portion of your research question Have a measurable, reproducible outcome measure or measures What makes a good quality hypothesis? It makes a prediction (you don t have to agree with the prediction). It describes the relationship between an independent (controlled) variable and a dependent (measured outcome) variable. It is feasible for the scope of your project. Examples of Hypotheses Chronic supplementation with omega-3 PUFAs reduces the incidence of sudden cardiac death. Dark chocolate intake is important for health status. Hospital readmissions are reduced when pharmacists participate in transition of care planning. 4

5 Independent and dependent variables? Chronic supplementation with omega-3 PUFAs reduces the incidence of sudden cardiac death. Dark chocolate intake is important for health status. Hospital readmissions are reduced when pharmacists participate in transition of care planning. How do you get from a hypothesis to specific aims? Hypothesis to Specific Aims Once you have a good hypothesis, it should lead directly to your aims. Brainstorm ways to test your hypothesis. Most hypotheses can be addressed in different ways, so don t limit your thinking too quickly (avoid love at first sight). 5

6 Hypothesis testing: Considerations for constructing aims Know your assumptions Know the limitations of your measurements CONTROLS, CONTROLS, CONTROLS Confounding variables can lead you astray Specific Aims PURPOSE: Specific Aims are the roadmap for the project. If you are going to measure it, it should be addressed in the aims. If you measure it, have a plan to use it. If you have an interesting idea that is not directly testing your hypothesis save it for later. How do you develop specific aims? Begin with the end in mind The specific aim or aims should be directly linked to the hypothesis. Each aim should be highly focused FEASIBILITY (time, resources, statistical power) 6

7 What should be measured? Surrogate Endpoints Optimal (True) endpoints Longevity Prevention of events (reduced morbidity) Improvement in quality of life Cost savings References: What if you don t have the time or resources to get to a true endpoint? Validation of surrogate endpoints Changes in the surrogate must predict a relevant clinical outcome AND Capture the effect of the intervention on the clinical outcome 1. DeMets DL and Califf RM. Lessons learned from recent cardiovascular trials. Part I. Circulation 2002; 106: Hilsenbeck SG, Clark GM. Surrogate endpoints in chemoprevention of breast cancer: guidelines for evaluations of new biomarkers. J Cell Biochem Supple 1993; 17G: Fleming TR. Surrogate markers in AIDS and cancer trials. Stat Med 1994; 13:

8 Surrogate Endpoints Benefits Shorter latency Reduced size/cost/duration of trials Avoidance of unethical practices May be more feasible Limitations Misclassification Assumes causality or close linkage to disease process May not be a complete picture (multi-factorial) Putting it all together Research question Purpose or Hypothesis Specific Aims What is measured? How is it measured? What are the controls? How will you interpret your data? Dark chocolate intake is important for health status. Better hypothesis: Dark chocolate intake improves HDL cholesterol. Specific aims: We will test the hypothesis that dark chocolate intake improves HDL cholesterol by 1. comparing % change in HDL cholesterol in patients assigned to 3 oz of daily dark chocolate. 8

9 Refining your aims Endpoint quality Review with colleagues, mentors Biostatistician Re-evaluate while looking at the hypothesis and the aims Is there anything you can delete? Is there anything missing? Think about the end of the study Specific Aim #1 We will test the hypothesis that dark chocolate intake improves HDL cholesterol by: 1. comparing % change in HDL cholesterol in patients assigned to 3 oz of daily chocolate. In this aim, XXX patients will be randomly assigned to either 3 oz of dark chocolate or 3 oz of milk chocolate daily for XX days. HDL cholesterol will be measured at baseline and after completion of the study. Possible confounders 9

10 CONTROLS Expected results Expected results (in my perfect world) 10