TIPS AND PEARLS OF CLINICAL RESEARCH DESIGN

Phillip Gordon(combined with art from

Nolaboneyards.blogspot.com)

ORDER OF EDITORIAL RIGORCase StudyCase SeriesReview (editorial, expert or topical)Cohort Cross Sectional StudySystematic ReviewCase Series with Systematic Review Cohort Comparison StudyBefore and After Cohort StudyMOOSE (pooled cohort studies) AnalysisProspective Clinical TrialRandomized, controlled clinical trialMeta-Analysis (pooled RCTs)

CASE STUDY: IT EXISTS, OR THIS IS EDUCATIONAL, OR WE HAVE UNIQUE DATACASE SERIES: RAISES ISSUES OF INCIDENCE, VARIANCE, CONFOUNDERSSystematic review: an attempt to formulate the literature for this disease entity, but what makes a review systematic? How do we satisfy an editor that our reviews are “systematic”. Can we do a systematic review as part of a case study or series?

A Cross Sectional Cohort Study: generally the way to estimate incidence and can usually be expanded from an interesting case series if your willing to put in additional work.

EXERCISE: you are hoping to submit a series of articles to SPETCRAL, the periodical of choice for professionals who want to make their mark in the fine art of necropsy. Your job is to take these drafts submitted to you by the boys from the bone yards and see if anything can be done with them…

Novel Crypt: examples can be found in several NOLA graveyards (but this one had spectral anomalies associated with it)

Unique Crypt: found only inSt Patricks

“A Cast Iron Family Style Tomb with a Spectral Anomaly”

“There are Five Cast Iron Family Style Tombs in New Orleans Graveyards but Only One with a Spectral Anomaly”

“A Complete Survey of the Number and Different Types of Cast Iron Tombs in New Orleans with Photographic Evidence of a Spectral Anomaly in One”

Which study has the best editorial value?

Consider the following Submission:

“Three Boneyard Boggarts present with disparate size ranges in the open crypts of some of New Orleans Cemeteries”

What is the main point of this submission and what type of study is it?

What are the chances we could do a systematic review?

Could we make it into a cross sectional cohort study to determine incidence?

What do you do with this one?

“Documentation of a Spectral Winged Woman Exiting a

Sealed Tomb”

What kind of submission is this?

Is the emphasis on the Winged Woman or on the Exit?

How do we figure out which is the more relevant emphasis

for the literature?

If we’re going to all this work, shouldn’t we get credit for it?

http://www.prisma-statement.org

Since 1999, with the QUORUM statement, systematic review in medical outcomes research has become standardized. The problem was that there were barriers to access of these standards (and methodologies). Today, with the 2009 release by PRISMA, all editors expect that systematic reviews and meta-analyses will follow a standard format. PRISMA = Preferred Reporting Items for Systematic reviews and Meta-Analyses

PRISMA flow diagram

There is also a published guideline specifically for the systematic review of observational (i.e. cohort and case series studies):

D.F. Stroup, J.A. Berlin, S.C. Morton, I. Olkin, G.D. Williamson and D. Rennie et al., Meta-analysis of observational studies in epidemiology: a proposal for reporting: Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group, JAMA 283 (2000), pp. 2008–2012.

However the PRISMA report now encompasses all systematic reviews (so the smart thing to do is quote both)

“Four Poltergeists Play with Broken Water Pipe”

“Poltergeists show a propensity for water sports”

“Poltergiests summoned by broken water pipe in New Orleans graveyard”

“Poltergiest manifestations associated with broken water pipe in New Orleans graveyard”

“Poltergeists subtly alter reality in New Orleans graveyard”

Which title is the best title and why?

What kind of submission is this?

So now let’s move on….

“ A Comparison of Greenwood Cemetery Crypt Longevity between those marked with Crosses verses those marked with the Star of David”

What kind of study is this?

“The Incidence of Front and Center Figurines in Single Occupancy Crypts in Greenwood Cemetery”

What kind of study is this?

“The Prevalence of Front and Center Figurines in Single Occupancy Crypts in New Orleans: based on a sampling of five cemeteries”

What kind of study is this?

What kind of study is this?

“Increased Lichen Growth Noted in Crypts Older than 50 years Following BP Oil Spill in two New Orleans Graveyards”

What kinds of study is this?

“English sparrow flight patterns most often mimicked nearby silhouettes on Sunday mornings during a 3 month study period.”

What kinds of study is this?

“A heat-tolerance comparison of blue versus red corrosion-resistant paints on random, aged, cast iron structures in New Orleans graveyards”

What kinds of study is this?

“A pooled analysis of heat-tolerance comparisons of different brands of blue versus red corrosion-resistant paints on random, aged, cast iron structures in New Orleans graveyards”

Its usefult to be able to read a title and know instinctively what kind of study your looking at. Let’s look at some real titles and see if we can decide what kind of study they represent?

Reactive arthritis to Clostridium difficile in a child.

New insights into spontaneous intestinal perforation using a national data set: (2) two populations of patients with perforations.

A randomized-controlled trial of prophylactic hydrocortisone supplementation for the prevention of hypotension in extremely low birth weight infants.

Let’s do some more:

Extravasation of hyperalimentation into the liver parenchyma from a peripherally inserted central catheter.

Understanding clinical literature relevant to spontaneous intestinal perforations.

Necrotizing enterocolitis during the first week of life: a multicentered case-control and cohort comparison study.

The Case Control Study

Whether using a series or small cohort, a comparison study can be formulated using matched controls. The is in the matching (age, sex, race, disease type, disease extent, medication exposures, etc.) such that as many variables as possible are matched – except the one which makes the test group different from the controls. From an editor’s point of view, a case control study allows a researcher to be less well powered if well matched (or to do a 2 or 3 to one matched if moderately well matched).

Which of the following is a case control study?

“Effects of Katrina Flood Waters on Brick versus Cement Cemetery Mausoleums within Two Nearby Cemeteries”

“Effects of Katrina Flood Waters compared between Brick Mausoleums and Geographically Paired Cement Mausoleums in Two Nearby Cemeteries”

“Effects of Katrina Flood Waters compared between Brick Mausoleums of St Lukes 1 with Cement Mausoleums in St Lukes 2 Cemetery”

Which of these studies has the worst design?

What is the underlying problem with all of these study designs?

Last Points:

1. When designing a study, always try for the best study you can produce (not the one requiring the least amount of work).

2. Know where your study fits into the literature. If you know that it has a place in the literature, then you can be confident that you will eventually get it published.

3. Know what the value and qualities of each study type are. Make it an instinct. That way you immediately know what a study can or can’t actually offer you in it’s conclusions.