how to properly plan and conduct research projects? farahnak assadi, md emeritus professor pediatric...

How to properly plan and conduct research projects?

Farahnak Assadi, MD

Emeritus Professor

Pediatric Nephrology

©2007 RUSH University Medical Center

1.Turn your ideas into research questions

2. Review the literature

3. Design the study and develop your methods

4. Writing your research proposal

5. Obtain ethical and trust approval

6. Collect and collate the data

7. Analyze the data and interpret the findings

8. Report on the study and the findings

• Decide on an area of research• What is your aim and

hypothesis?• Where do I start?• Libraries• Links to useful websites

• Participant involvement• Statistic issues• Collaboration

• Peer review• Sponsor issues

• Why ethics are so important?• Prepare consent forms• Contact your RD office

• Issues to consider• Data protection and

confidentiality • Data analysis• Interpreting data

• Publishing your research• Future direction

Research Process Flowchart

Turning your ideas into research

• Stay up to date on the area of specific research

• Keep up with the current literature on the area of your research proposal

• Avoid duplicating what is already known• Be creative and develop a new idea


Review the literature

• Where do I start?

- Discuss with your mentor

- Start reading

- Identify the most important gaps in knowledge

and prioritize the unanswered questions about

your research

• Libraries• Links to useful websites

- PubMed, MEDLINE, etc



Review literature (cont’d)

• Isolated persistent asymptomatic hematuria occurs in about 2%-3% in school age children

• It is the most common laboratory finding of renal disease


isolated asymptomatic hematuria

• No proteinuria on dipstick-test• Normal BUN and serum creatinine levels• Negative TB test• Normal serum C3, C4, CH50• Ca/Cr ratio <0.22• Normal renal ultrasound• Negative urine culture


Consider other causes

• Benign hematuria (TGBM disease ) • IgA nephropathy• Alport’s syndrome

• 51%

• 49%• 1.0%


To do the kidney biopsy!

• A policy of recommending renal biopsy for the diagnosis of isolated persistent hematuria would lead to a large number of patients with benign hematuria (51%)


Not to do the kidney biopsy!

• A policy of deferring renal biopsy in all patients until more overt signs of a progressive nephropathy develop may delay the appropriate management of a chronic kidney disease (49%)


To do or not to do biopsy?


Hypothesis

• Inflammation is an important risk factor in the initiation of HTN, CVD, CKD, and stroke in both diabetic and non-diabetic patients

• Microalbuminuria (MA/Cr >30 mg/g) is a sensitive marker of inflammation and a powerful predictor of CKD, particularly in nephropathy due to diabetes


Spesific aim

• To investigate the value of urinary microalbumin excretion in predicting glomerular abnormalities in children with isolated persistent hematuria

Design the study and develop a method

• Decide on a general area of interest• Why does this area interest you?• What is your aim?• What is you hypothesis?• Is your idea novel?• How will patients benefit from your research?• Consult colleagues and other researchers


Obtain ethical and trust approval

• Why ethics are so important• Applying to a research ethics committee• Prepare consent forms

- Prepare information sheet checklists

- Prepare consent form

• Contact your RD office


Collect and collate the data

• Issues to consider - Beware of biases

- Seek statistical advice if necessary

- Researchers must bear the day-to-day responsibility

for the conduct of research

• Data protection and confidentiality

- Identities should be avoided by use of codes

-


Analyze and interpret the data

• Quantitative data analysis

- Identifying a data entry and analysis

manager (SPSS)

- Coding data

- interpreting data

• Qualitative data analysis

- Familiarization with the data

- Development of provisional categories

- Development of theory and incorporation of pre-

existing knowledge



-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Patients MA/Cr< 30 ug/mg MA/Cr> 30 ug/mg

N 54 (71%) 22 (29%)*Age, yrs 13 + 5 12 + 4

Female/Male (n) 20/16 19/21 Body mass index (kg/m2) 24 + 3 25 + 2 Systolic BP (mmHg) 122 + 7 120 + 11

Serum Cr level (mg/dl) 0.5 + 0.2 0.6 + 0.2

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

*p=0.002

Table 1. Patients characteristics in relation to MA

Results


Results

MA/Cr< 30 μg/mg• Normal tissue 50%• TGBM 28% • IgA GN: 2%

MA/Cr> 30 μg/mg• IgA GN 91%• 9% TGBM 9%

Table 2. Glomerular lesion in relation to MA


Fig 1. MA and glomerularl lesion

IgA (n=21) TBMD (n=17) Normal (n=38)

MA

/CR

(u

g/m

g)

100

90

80

70

60

50

40

30

0

P=0.002


Fig 2. MA and glomerular lesion

0

10

20

30

40

50

60

70

80

90

100

IgA

TBMD

Normal

glom

erul

ar le

sion

(%

)

MA/Cr >30 MA/Cr<30

MA/Cr μg/mg


Conclusions

• Routine measurements of urinary MA is warranted in children with isolated persistent hematuria

• Screening for MA usually predicts a specific morphologic type of glomerular disease

• It may help to identify a subgroup of patients who are at higher risk for IgA nephropathy and could benefit early therapy and closer follow-up


Conclusions (cont’d)

• A renal biopsy should be considered in the child whose microscopic hematuria is associated with MA

• Children with isolated hematuria and strong family history of benign hematuria, in the absence of MA may not require a renal biopsy to confirm the diagnosis

Report on the study

• Publishing your research findings

- Research is conducted for the benefit of patients,

health care providers, and the public in general

- Inform the participants of your research

• Presenting for conferences and seminars

• Assadi F. Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria. Pediatr Nephrol 2005; 20:1131-1135


Turning ideas into a research question

• Association between hyperuricemia and essential hypertension among children and adolescents.


Turn your idea into research

• Essential hypertension (EHTN) is frequently associated with hyperuricemia in both adult and pediatric patients.

• More than 80% of children with essential HTN have serum uric acid (UA) levels above 5.5 mg/dL

• Elevated UA level is a predictor of incident HTN and cardiovascular disease.

• UA causes HTN in a rat model through the activation of the RAS, down regulation of nitric oxide, and vascular endothelial dysfunction.

Hypothesis

• Treating EHTN with usual antihypertensive agents does not completely reduce cardiovascular risk related to uric acid (UA) levels.

• Lowering serum UA levels with allopurinol may provide greater benefit than simply treating HTN with the conventional therapy.

• Feig DI et al. JAMA 2008;300:924-932

Purpose of the study

• To investigate the potential therapeutic effects of UA-lowering agent, allopurinol in combination with an ACE inhibitor on BP in hyperuricemic children with newly diagnosed EHTN.

Design the study and methods

• Participant involvement• Study design and sampling

- What method will give the most useful data?

- What is the probability and non-probability of

sampling method?• Research methods

- Choosing qualitative and quantitative methods• Statistical issues

- Online statistics textbook from “www.Statsoft.com”• Collaboration with other researchers


Patients referred for the evaluation hypertension (n=118)

Excluded (n=47) • Prehypertension (n=23) • Abnormal urinalysis (n=11) • Stage 2 hypertension (n=5) • Hydronephrosis (n=4) • Cystic kidney disease (n=2) • White coat hypertension (n=1) • Pheochromocytoma (n=1)

Patients with stage 1 hypertension (n=71)

Excluded (n=19)Serum uric acid <5.5 mg/dL

Patients randomized (n=52)

Enalapril plus allopurinol (n=28)

Excluded (n=4) • poor compliance (n=4)

Excluded (n=4) • Poor compliance (n=3) • stage 2 hypertension

Completed 8 weeks study and included in analysis (n=20)

Completed 8 weeks study and included in analysis (n=24)

Enalapril (n=24)

Characteristic Enalapril therapy(n=20)

Combination therapy (n=24)

P value

Gender (N) Male (12)Female (8)

Male (13)Female (11)

NSNS

Age (year) mean (range)

14.2 (12-17) 15.9 (12-19) NS

BMI (percentile)mean (range)

88 (85-99) 92 (89-93) NS

Serum UA (mg/dL) mean (range)

6.6 (6.0-7.3) 6.8 (6.2-7.1) NS

Systolic BP (mmHg)mean (range)

133 (129-136) 134 (128-137) NS

Diastolic BP (mmHg)Mean (range)

85 (82-86) 86 (80-87) NS

Baseline characteristics

Parameter Enalapril therapy (n=20)

Combination therapy (n=24)

P value

Change in systolic BP (mmHg)

-4.3 (-2.1 to -6.7) -8.2 (-7.2 to -9.8) 0.001

Change in diastolic BP

-2.4 (-1.1 to -2.2) -6.3 (-1.9 to -7.8) 0.006

Serum uric acid (mg/dL)

-3.3 (-2.9 to -5.2) -5.1 (-5.8 to-6.7) 0.002

Results

Conclusions

• Allopurinol enhances the BP lowering effect of enalapril in hyperuricemic adolescents with stage-1 primary HTN by reducing serum UA level.

• Treatment regimen that lowers serum uric level may be indicated to decrease the incidence of CVD by reducing serum UA level.

• Assadi F. Allopurinol enhances the blood pressure lowering effect of enalepril in children with hyperuricemic essential hypertension. J Nephrol 27:51-56

Future Direction

• Increased dietary intake of fructose, which is a known cause of hyperuricemia, may be contributing to the current epidemic of obesity and HTN.

• Ongoing clinical trials will elucidate the role of UA in human HTN and will determine whether control of UA may be a new way to prevent or treat essential HTN.


1.Turning your ideas into research questions

2. Review the literature

3. Design the study and develop your methods

4. Writing your research proposal

5. Obtain ethical and trust approval

6. Collect and collate the data

7. Analyze the data and interpret the findings

8. Report on the study and the findings

• Decide on an area of research• What is your aim and

hypothesis?• Where do I start?• Libraries• Links to useful websites

• Participant involvement• Study design and methods• Statistic issues• Collaboration

• Starting your research proposal• Peer review• Sponsor issues

• Why ethics are so important?• Prepare consent forms• Contact your RD office

• Issues to consider• Data protection and

confidentiality • Data analysis• Interpreting data

• Publishing your research• Future direction

Research Process Flowchart

how to properly plan and conduct research projects? farahnak assadi, md emeritus professor pediatric...

Documents

area of research

data entry

data development

research proposalavoid

research questions2

research proposal5

dataquantitative data

conduct research projects