From clinical observation to research study design: THINKING LIKE A SCIENTIST

1. From clinical observation to research study design:THINKING LIKE A SCIENTIST What can I get published?? Objectives for the day: By the end of the seminar the participant will have Applied the 5 Why’s to a clinical research question. Developed an innovative and novel research question. Begun the process of moving from a research question to designing a research project.

2. Clinical Observations • Keen observation • Receiving knowledge of the outside world through the senses • Crucial first step • Pattern recognition • Cognitive process of recognizing the unfolding performance of a set of events or actions (stimuli) so as to be able to anticipate change, challenge and eventually seize an opportunity to react . . . and possibly to break the pattern. • It is a basic animal instinct, but it would appear that if we spend too much time in our narrow zones of high expertise we risk to lose the habit.

3. Peer Interactions • Group think • Talk to people about their research & your research as much as possible! • Keep an idea notebook - Write it all down • I wonder why???? • Connecting the Dots • Some of the greatest discoveries are due to cross disciplinary “connections” • Try to connect every seminar to your research interests no matter how diverse • Challenge yourself to come up with one question for each seminar speaker.

4. I wonder??? • 5 Whys • A questions-asking method used to explore the cause/effect relationships underlying a particular problem. • The goal is to determine a root cause of the problem. The Problem: Your car will not start. 1- Why? - The battery is dead. 2- Why? - The alternator is not functioning. 3- Why? - The alternator belt has broken. 4- Why? - The alternator belt was well beyond its useful service life and not replaced. 5- Why? - The vehicle was not maintained according to the recommended service schedule. (a root cause) 6- Why? - Replacement parts are not available because of the extreme age of the vehicle. (next step) Solutions: Start maintaining the vehicle according to the recommended service schedule. (5th Why solution) Purchase a different vehicle that is maintainable. (6th Why solution)

5. Caveats to 5 Whys • Tendency for investigators to stop at symptoms rather than going on to lower level root causes. • Inability to go beyond the investigator's current knowledge - can't find causes that they don't already know. • Lack of support to help the investigator to ask the right "why" questions. • Results aren't repeatable - different people using 5 Whys come up with different causes for the same problem. • Tendency to isolate a single root cause, whereas each question could elicit many different root causes.

6. An example The Problem: Children with severe sickle cell disease are not aggressively managed until after they have several re-current VOCs. 1- Why? – There is no way to identify them pre-emptively. 2- Why? – There are no serum or genetic markers identified. 3- Why? – The focus has been on vascular components of the disease and pain has been ignored as an expected downstream event instead of as a active event. 4- Why? – There has been an under-appreciation of the role of the nervous system peptidergic afferents in an over-lapping manner with vascular reactivity and pain. 5- Why? – Dogma was that peptidergic nervous system afferents have little to do with acute VOCs. (root cause) Solutions: So we have a novel and innovative area of research study if we look at VOCs and genetic markers from a pain-centric perspective. Caveat: Getting funded can be hard if you are too far outside of the dogma.

7. 5 Whys • Ideas from invited speakers • The problem: Our patients in the free clinic have poor health literacy. • The problem: Our patients in the free clinic are diabetic and overweight and not adherent to therapeutic management. Frame this in terms of the basic science research findings from Dr. Grillo’s lecture. • Ideas from our own faculty • The problem: Surgeons are infusing incisions with local anesthetic prior to suturing. • The problem:

8. Brainstorm:Observation, Pattern, Why? 2. Intervention (+/- comparison) 1. Target Disorder 3. Outcome

9. Step 1: Question • Come up with a focused Question • One of the fundamental skills required for practicing EBM is the asking of well-built clinical questions. • To benefit patients and clinicians, such questions need to be both directly relevant to patients' problems and phrased in ways that direct your search to relevant and precise answers. • In practice, well-built clinical questions usually contain four elements.

10. Step 1: Question (PICO)

11. Step 2: Literature Search Step 1:Create a search strategy Scenario: A 64 year old obese male who has tried many ways to lose weight presents with a newspaper article about ‘fat-blazer’ (chitosan). He asks for your advice. PICO Question: In obsese patients, does chitosan, compared to a placebo, decrease weight.

12. Step 2: Literature Search Step 2: Convert PICO question into a search strategy • Underline the key terms – those most specific to your question • Number the PICO elements in order of importance from 1-4 • Think of alternate spellings, synonyms and truncations ‘*’ is a truncation symbol that means further letters can be added to the word OR finds studies containing either of the specified words/phrases, and broadens your search AND finds studies containing both specified words/phrases, and narrows your search

13. Step 2: Literature Search Step 3: Searching • Summaries of the primary evidenceACP Journal Club | Clinical Evidence | Dynamed| eMedicine | Essential Evidence Plus | FPIN Clinical Inquiries | UpToDate • DatabasesPubMed | Cochrane Library | Center for Reviews & Dissemination: • Electronic textbooks and librariesAccessMedicine | ACPMedicine | ACP PIER | Stat!Ref | MDConsult http://www.ncbi.nlm.nih.gov/pubmed/

14. Step 3: Assess Validity of Literature • Are the results of the study valid? Randomized Blinded Comparison groups similar in prognostic factors Follow –up complete Analyzed according to starting allocation

15. Step 3: Assess Validity of Literature • What are the results? How large was the treatment effect? What was the relative risk reduction? What was the absolute risk reduction? How precise was the estimate of the treatment effect? What were the confidence intervals?

16. Step 3: Assess Validity of Literature • Will the results help in caring for my patient? Were the study patients similar to my population of interest? Does your population match the study inclusion criteria?If not, are there compelling reasons why the results should not apply to your population? Were all clinically important outcomes considered? What were the primary and secondary endpoints studied?Were surrogate endpoints used?Are the likely treatment benefits worth the potential harm and costs?What is the number needed to treat (NNT) to prevent one adverse outcome or produce one positive outcome?Is the reduction of clinical endpoints worth the increase of cost and risk of harm?

17. Step 4: Write a paper Review Systematic Review Meta-Analysis

18. Step 4: Write a paper

19. Now that you have a research question Step 5: Study Design How do you turn it into a fundable research project? Identify potential funding sourceS. Go after low hanging fruit first! Use your new investigator advantage!

20. Step 5: Study Design Identify your specific aims (typically 2-3) • Demonstrate that you have the techniques/patient population • Demonstrate that the project is going to be successful • Rule of thumb: preliminary data/feasibility results for each of the specific aims. • These need to be focused and very specific! • NO FISHING EXPEDITIONS! Identify the key preliminary data you need to generate! Plan to get your biggest BANG for your Buck!

21. Any Questions?