The Anatomy of a Protocol

• Background• Research Question (hypotheses)• Design• Study Population• Measurement

– Predictors (intervention)– Outcomes– Confounders (Randomization integrity)

• <Procedure>• Analysis• Relevance/Contribution

Research ProtocolPage Allocation

Background and Model 4 1/2 pages

Research Question/Hypothesis 1/4 page

Design 1/2 page

Study Population 1/2 page

Measurement 4 pages

Predictors (intervention)

Outcomes

Confounders (randomization integrity)

Procedure

Analysis 1/2-1 page

Ethics/Relevance/Contribution 1/2 page

Your argument needs to leave the reader with the following impression:

This is an important question to answer (it may also be interesting?)

We need to know the answer to this question because…….

it will have an impact on ____________ it will change _____________________

We do not know the answer to this question.

The question can be answered by this study.

THE ARGUMENT PARADIGM

The Big Picture how big is the problem? burden of morbidity/mortality impact on quality of life? productivity? cost of problem __________________________________________________

Where does your question fit in?Is it a logical next step?

burden of illness determinants interventions cost ____________________________________

What will your question answer that isn’t known already?

Fill a hole

(no one knows and we needto know because it could make a difference)

Better mousetrap

(no study to date has adequatelyanswered the question, the right answer could change how we do things, this study can/will solve this problem)

Your question!

The Research Cycle

Burden of disease

Causation Determinants

Efficacy

Effectiveness

Efficiency

Implementation

After P Tugwell, 1985

Measurement

PAGE ALLOCATION

The Big Picture How big is the problem? Burden of morbidity? Impact on quality of life? Productivity? Cost of problem?__________________________________________________________

Where does your question fit in? Is it a logical next step? Burden of illness Determinants Interventions Cost _________________________________________________________________

What will your question answer that isn’t known already?

Fill a hole

(no one knowsand we need to know because it could make a difference)

Better mousetrap

(no study to date has adequately answered the question, theright answer couldchange how we dothings, this study can/will solve this problem)

GETTING STARTED

Decide what you want to know from reviewing the literature

sketch out the logic of your argument and find the related lit

OR

read some review articles to get a handle on the area, the assumptions, the unknowns

Summarize as you go – the key elements?

Having problems? Figure out why?

question is not well defined? you have too many questions? your question is at the wrong part of the research cycle?

Author Year Patients Design (confounder adjustment)

Exposure Risk Estimate

Risk of Hip Fracture in Relationship to Psychotropic and Other Drug Use

MacDonald {337}

1977 390 cases case series (no adjustment)

barbiturate 93% with hip fracture used barbiturates as a hypnotic

Rashiq {988} 1986 102 cases204 controls

case-control(age, sex match)

any drugpsychotropicdiuretic

0.42 (.26,.67)0.84 (.41,1.73)0.38 (.20,.72)

Ray {1120} 1987 1021 cases5606 controls

nested case-control(design: sex, age, ace, location

antipsychoticsantidepressanthypnotics-long hypnotics-short

2.0 (1.6, 2.6)1.9 (1.3, 2.8)1.8 (1.3, 2.4)1.1 (0.8, 1.6)

Taggart {334}

1988 282 cases145 controls

case-control(no adjustment)

sedativesNSAID

1.08 (NS)0.32 (p<.001)

Ray {984} 1989 4501 cases24,041 controls

nestedcase-control(design: sex, age, index date)

Long-acting benzosshort-actingbenzos

1.7 (1.5, 2.0)1.1 (0.9, 1.3)

Stevens {1123}

1989 173 cases134 controls

case-control(in analysis: age, sex, location, widow, bodyweight, smoke, dementia, stroke, arthritis, diabetes, drugs)

benzodiazepinetranquilizersthiazidesnonthiazides

1.03 (0.6,1.8)1.62 (0.6, 4.1)1.11 (0.6, 1.9)0.82 (.5, 1.4)

Grisso {1117}

1991 women ≥ 45 yrhospital admitscases=174controls=174

case-control(design: age, hospitalanalysis: age, LE dysfunction, vision, stroke, body mass, alcohol, meds)

Significant Risk FactorsLE dysfunctionvisionstrokebody masslow, mid, high

1.9 (0.9, 3.8)4.8 (1.4, 16.2)4.5 (1.5, 13.5)1.00.4 (0.2, 0.9)0.2 (0.1, 0.5)

Appendix 1: A Summary of Studies Which Have Examined the Relationship between Benzodiazepines,Psychotropics and Injury in the Elderly

Functionalities, Use and Benefits from E-Rx systems (Level 1=drug reference alone, Level 2=rx writer, no med history, Level 3=rx writer integrated with alerts, demographics, formulary info, allergies, Level 4=rx-writer and tracking of meds, Level 5=rx-writer and connectivity between MDs, pharmacists and payers, Level 6=EMR integration)

Author/yr Locale/journal Level of System Utilization Data

Ter Wee/1993

UK (Br. J Gen Practice)

Level 3(rx-writer, demog from practice info system, enter disease for drug list, drug interactions)

None

Proost/1992 Netherlands (Compu Biol. Med)

Level 1(stand-alone drug reference that permits entry, storage and search for patient drug hx, demographics, renal function, weight, and dose recommendations for 180 drugs)

none

DeLeo/1993 U.S (Am J Hosp Pharm)

Level 1(self-administered, computerized patient medication history taking structured interview-demographic, diseases, medication list, compliance, symptoms, allergies, psychosocial-output format for inclusion in chart)

ACCEPTABILITY20 patients, mean age 41.7 yrs., mean completion time=40 minutes; validated by pharmacist interview (no actual data), incomplete/wrong data in 3/20

De Zegher/1994

Belgium, France, Italy (Computer Methods and Programs)

Level 2(standalone rx system that allows entry and storage of demographics, and dx)

none

Purswani, 1995

U.S. (MD Computing)

Level 1(drug knowledge base-searchable monographs in hierarchical structure)

ACCEPTABILITY5/6 residents found easy to use without training

Puckett1995 U.S in-patient (Am, J Hosp Syst Pharm)

Level 5CPOE system-with bar-coded verification at time of dispensing (drug+ patient)-no DSS

PROCESSReduction in hospital wide annual rates of med errors (except wrong patient) relative to doses dispensed by 0.17% to 0.7% (yr 1) and 0.5% (year 2)

Berard, 1996

U.S in-patient oncology(Am, J Hosp Syst Pharm)

Level 5-6CPOE system for oncology drug management

PROCESSClaims of no oncology drug errors but no method described

McCullin, 1997

U.S. in-patient (Am, J Hosp Syst Pharm)

Level 1-4Computerized rules used to review doses dispensed for 35 drugs relative to patient demographics and creatinine clearance, reports sent to hosp pharmacists whp contacted MDs to fix problem

PROCESSOf 28,528 orders, 2,859 (10%) had problems. Lower dose recommended in 1,992 (70%), and higher dose in remainder, MDs contacted for 1163 (41%) of alerts. Altered dose in 868 (75%) cases

Gronroos, 1997

Finland-inpatient

Level 1Drug interaction assessment system

PROCESS BASELINEAmong 2,457 inpatients, 326 serious interactions detected in 173 patient (6.8%); calcium and fluroquinolones most common (n=66)

Example

• Objective

To estimate risk of hospital admissions for cardiovascular and respiratory diseases associated with PM10-2.5

exposure, controlling for PM2.5.

• Background