Yo Your ur Fi Findings dings Leo Buckley, ley, PharmD mD - - PowerPoint PPT Presentation

Research search In Inside ide and d Ou Out: t: How w to to Ask th the Rig ight ht Qu Question, estion, Ge Get t th the Best t Answer swer and d Publish blish Yo Your ur Fi Findings dings

Leo Buckley, ley, PharmD mD Brigham and Women’s Hospital Boston, ton, MA

Di Disc sclosur losure: e:

This presentation is based upon available evidence, published expert

• pinion and my own personal anecdotes

Ou Outcome tcomes s of f Reside sidency ncy Research search Projects jects

Publication Rates of Residency Abstracts Published Unpublished

5 10 15 20 25 Months

Median Time to Publication of Resident Research

IRB Data Collection Analysis Publication

McKelvey, AJHSP 2010 Olsen, AJHSP 2012

Lim imitin iting g Fa Factors tors Associated

• ciated wit

ith h Resident sident Resea search rch

• Selection (design) of a project unsuitable for publication
• Lack of knowledge of the publication process
• Manuscript rejection
• Time constraints
• Limited mentorship for the trainee
• Lack of trainee interest in a project
• Lack of perceived benefit associated with publishing
• Financial constraints for statistical support or publication fees
• Trainee departs without completing manuscript

Deal, Pharmacotherapy 2016

Se Sele lection ction (d (desig esign) n) of

• f a pro

a project ject un unsui suitable table fo for pu r publ blicatio ication

Matching tching th the Siz ize e of Yo f Your ur Qu Question stion to to th the Siz ize e of f Your ur Answer wer

• Does Drug A reduce mortality?
• Focus on a specific knowledge gap
• Helpful framework: write down the question and your

hypothesized answer

• Does the use of an IV furosemide dosing algorithm lead to consistent

diuretic response in patients with heart failure and congestion?

• We hypothesize that diuretic response, as measured by 3-hour urine
• utput, is similar across patients with varying characteristics and oral

diuretic usage.

Envisioning isioning what at your r stu tudy dy wil ill l produce

• duce
• You should be able to write the abstract, tables and figures

before starting the study.

Wh What at is statist atistical ical po powe wer?

• Definition: power = 1 – β

where β is the probability of concluding that there is no significant effect, when in fact, there is a real effect i.e., your drug worked, but your statistics failed so, power is the probability of finding the effect that you think exists

Wh Why y do I ne I need ed to to est stimate imate sa sample mple si size ze?

Buckley Curr Emerg Hosp Med Rep 2016 ~17.5% absolute difference!!!

Wh Why do I n I need ed to to esti timate mate sampl mple e siz ize? e?

• Assuming a 30% rate in the bridge group and a 12.5% rate in

the no bridge group (which is a huge difference), enrollment of 38 participants in the no bridge group and 17 in the bridge group provides about 32% power to detect a significant difference.

• So, if there really is a 17.5% difference between the bridge and

no bridge groups (which is very unlikely anyway), then my study as designed would detect the 17.5% difference about 1 in every 3 times on average.

Ho How w do do I es I estimate imate sam ampl ple e size? ze?

• 1. Recall that sample size estimations are estimates
• 2. Guess the average in the treatment group
• 3. Guess the average in the control group
• 4. Guess the variability of the between-group difference in the

treatment and control group

• 5. Plug your estimates into at least TWO sample size estimators

(powerandsamplesize.com)

• 6. Repeat using different averages and variabilities

An An ex exam ample ple po powe wer es estimati imation.

• n.

in a Randomized Clinical Trial SD Between-Group GLS Change (%)

• 2.2
• 2.5
• 2.7

2.7 85% 92% 95% 3.0 78% 87% 92% 3.5 65% 76% 82% CRP=C-reactive protein; SD

What if I can’t enroll the optimal number

• f

f subjects? jects?

• Change your endpoint: continuous endpoints are more sensitive

to change than categorical endpoints

• Change in hemoglobin
• Combine categorical endpoints (30%  65% power):
• Major bleeding = ~20% of patients
• Major or clinically relevant nonmajor bleeding = ~35% of patients
• Net clinical benefit (major or clinically relevant nonmajor bleeding or

any stroke or systemic embolism) = ~40% of patients

• Use a case-control study design

Ca Case-Contro Control l St Stud udies es

Cases

Exposure(+) Exposure(-)

N=200 N=50

Odds of exposure for cases = 200 / 50 = 4:1 Odds ratio for cases vs. controls = (4/1) / (1/2) = 8

Controls

Exposure(+) Exposure(-)

N=50 N=100

Odds of exposure for controls = 50 / 100 = 1:2

Co Coho hort t St Stud udies ies

Exposure(+) Exposure(-) All Patients

• f Interest

Controls Cases Controls Cases N=200 N=125 N=20 N=100 Probability=125/200 Probability=20/100 Relative risk=125/200 20/100

How w to to decide ide between tween a case-cont control rol stu tudy dy and d a cohort hort stud tudy? y?

Case-Control

• Good for rare outcomes
• Good for outcomes that occur

years after exposure

• Very feasible
• Who is in your control group?
• You need a quick answer (i.e.,
• utbreaks)
• Unsure of the disease incidence

Cohort

• Bad for rare outcomes
• Your exposed and unexposed

groups are derived from the same

• verall sample
• Can estimate disease incidence

Wh Which h statist atistical ical tes est t do do I us I use? e?

Slide courtesy of William Baker PharmD, UConn Alternatively, could use regression models to adjust for confounders

Wh Wher ere e do does es the he da data a com

• me

e from

• m?

F e m a le M a le O th e r M is s in g

1 0 2 0 4 0 0

A d ju d ic a tio n o f S e lf-R e p o rte d F e m a le P a rtic ip a n ts in H e a lth L N K

S e x in H e a lth L N K N u m b e r

4 0 8 4 21 5

Ahmad A, et al. Circulation 2017;136:1207-16. W h ite As ia n B la c k H is p a n ic O th e r M is s in g

5 0 3 0 0 4 0 0

A d ju d ic a tio n o f S e lf-R e p o rte d W h ite P a rtic ip a n ts in H e a lth L N K

R a c e /E th n ic ity in H e a lth L N K N u m b e r

3 4 4 1 2 12 79 1

IC D -9 , M e d s a n d B P M is s in g IC D -9 M is s in g M e d s M is s in g B P IC D -9 o n ly M e d s o n ly B P o n ly

5 0 1 0 0 1 5 0

A v a ila b ility o f H y p e rte n s io n IC D -9 C o d e s , A n ti-H y p e rte n s iv e M e d ic a tio n U s e a n d B lo o d P re s s u re M e a s u re m e n ts in H e a lth L N K

D a ta A v a ila b ility N u m b e r

Ahmad A, et al. Circulation 2017;136:1207-16.

Good! Bad! Huge problem!

Hogan 1997 JAMIA Chan 2010 Med Care Res Rev

Potential tential Probl

• blems

ems wit ith h Mic icrosoft rosoft Excel cel

• No tracking
• Excel does not care if you delete a value by accident
• Excel does not care if you sort the data incorrectly
• Excel does not care if you copy and paste incorrectly
• Excel does not care if you add a column for new data and delete

another

• Excel does not care if you enter “1300” for systolic blood pressure
• Excel does not care about missing data

Using ing Mic icrosoft rosoft Excel el fo for Data ta Coll llection ection

• Create a new version each time you open your Excel

spreadsheet and track what you did each time and who did it

Using ing Mic icrosoft rosoft Excel el fo for Data ta Coll llection ection

• Always double check Excel after you ask it to do something
• Sorting rows – did you select all columns or just some?
• Performing calculations – did you select the right area? Did you use the

right command?

Using ing Mic icrosoft rosoft Excel el fo for Data ta Coll llection ection

• Use specific terms for missing data vs. data that you haven’t

collected yet

• “NA” = I looked and it’s not there

Cl Clea ean n you

• ur da

data

• Check the 5 or 10 highest and lowest values for outliers, check

for missing data, spot check cases to make sure you didn’t sort incorrectly

Da Data a Co Collection ection So Software ware

La Lack ck of

• f kn

knowledge

• wledge of
• f th

the e pu publ blicati ication

• n pr

proces

• cess

Ma Manuscript nuscript re rejection ection

Au Autho horship rship

• Why is it important?
• Getting credit – people want to be authors
• Taking responsibility – people have to be authors

Au Autho horship rship

• First author: person who does the bulk of the work
• Second author: person who does a lot of the work
• Middle authors: people who contributed deeply in specific areas
• r broadly to the overall study
• Last author: senior author, person who provided oversight and

direction of the study, group leader or principal investigator

• Corresponding author: someone who can speak on behalf of

the authors

Au Autho horship rship ex exam ampl ples es

First Middle Last Corresponding Your mentor designed the study, you did the work, you both drafted the manuscript, your collaborators helped You Collaborators Mentor Mentor You designed the study, did the work and drafted the manuscript, your mentor provided guidance and your collaborators helped You Collaborators Mentor You You designed a study, provided oversight to someone else and had help from

• thers

Your trainee Collaborators You You You helped your friend complete their project Your friend or their trainee Your friend’s collaborators and you Your friend

• r their

mentor Your friend, their trainee or their mentor

Av Avoi

• iding

ding Au Autho horship rship Issu sues es

• Pre-specify criteria for each authorship role and the person

expected to fulfill that role

• Agree that authorship is granted for work done, not work

expected to have been done

• Pick your battles – is it worth arguing over middle authorship?
• Expand the pie: is there a follow-up study that will be

performed? The work can be divided differently in the future.

• Authorship “contracts” or “agreements”

Shari aring ng your ur results ults wit ith h th the broader

• ader

community munity

• Abstracts and poster presentations
• Manuscripts
• Full length manuscripts – for a major finding and smaller, but related

findings

• Letters and short reports – usually report a single, major finding

Ma Manu nuscript cript time melin line

1. Identify a target journal 2. Format the paper for the target journal (abstract, key words, disclosures, double- spacing, reference format, figure format, etc.) 3. Enter all the information into a website and submit for review 4. Managing editor requests that you include the volume and issue in references, not just volume 5. Re-submit for review 6. Editor or associate editor reviews your manuscript, one of several dozen to be reviewed that week 7. Editor or associate editor rejects your manuscript or sends to external peer reviewers 8. External peer reviewers see the email invitation and answer it 1 week later 9. External peer reviewers submit review on the day it’s due

• 10. Your receive the comments and respond to each of them (make sure to redline and

underline additions and blue strikethrough deletions)

Ma Manu nuscript cript time melin line e (cont

• nt.)

.)

10.Re-submit your revised manuscript to the journal 11.Wait a couple weeks 12.Get rejected and resubmit somewhere else or get additional revisions or get accepted

1 2 3 4 5 6

2012 2013 Annals of Family Medicine Journal of General Internal Medicine Southern Medical Journal (v1) Southern Medical Journal (v2) Southern Medical Journal (v3) Current Hypertension Reports

Impact Factor / General Well-Being of Authors

2016 2014-2015

Ho How w do do I wri I write e a d a disc scussio ussion n sec ection tion?

1st paragraph: summary of your findings

In this retrospective cohort study, we found that the use of Drug A was associated with an increased risk of hyperkalemia compared to Drug B. This association was consistent across all

• subgroups. These results suggest that / indicate the need for …

Middle paragraphs: interpretation of important or interesting results; previous literature

We found that the risk of hyperkalemia did not differ between patients with and without chronic kidney disease. This unexpected observation may be attributed to …

Second to last paragraph: limitations (do not shoot yourself in the foot unless asked)

Outcomes were identified using ICD codes rather than manual adjudication.

Last paragraph: conclusions

One or two clear statements that describe your main findings and the implications. Our finding of an increased risk of hyperkalemia associated with Drug A suggest that …

Ho How w do do I re I respon pond d to

• rev

eviewers? ewers?

Be respectful to the reviewers, who are volunteers trying to advance science, and make their lives relatively easier.

Additi tiona

• nal

l Re Resourc rces: es: