EAL

MNT: Comparative Effectiveness of MNT Services (2009)

Citation:

Smith LK, Luepker RV, Rothchild SS, Gillis A, Kochman L, Warbasse JR. Management of type IV hyperlipoproteinemia: evaluation of practical clinical approaches. Annals of Internal Medicine. 1976; 84: 22-28.

PubMed ID: 1106289

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To determine how a sizable population of subjects with hyperlipoproteinemia can be most effectively and efficiently identified and treated.

Inclusion Criteria:

Subjects with type IV hyperlipoproteinemia
Aged 20 to 49 years
Subjects who were obese, who admitted taking a moderate consumption of alcohol and who took birth control pills or conjugated estrogen were not excluded.

Exclusion Criteria:

Different age range
Other types of hyperlipoproteinemia
Evidence of cardiovascular disease
Lipid values possibly affected by poorly controlled or insulin-dependent diabetes
Idiopathic hypercalcemia
Abnormal serum protein patterns
Alcoholism
Taking lipid lowering agents.

Description of Study Protocol:

Recruitment

Heart Disease Prevention Program conducted by the Cardiovascular Service of the Baltimore US Public Health Service Hospital and the Employee Health Service, US Social Security Administration screened 4,000 Social Security Administration employees in one year for abnormal findings by fasting serum triglyceride and cholesterol measurements, electrocardiogram, chest X-ray, blood pressure and cardiovascular questionnaire.

Design

Randomized controlled trial. Randomization methods not described.

Intervention

Group A: Treatment by clinic nutritionist and physician with the National Heart and Lung Institute type IV diet for six weeks, followed by diet plus clofibrate (500mg four times per day) for the remaining 18 weeks. The nutritionist conducted two group instructions at the start and individual meetings with participants every two to three weeks during the course of the study.
Group B: Same treatment by private physician
Group C: No intervention for 24 weeks, with subjects advised of abnormality.

Statistical Analysis

Group comparisons made through matched or paired Student's T-test.

Data Collection Summary:

Timing of Measurements

All groups measured at baseline. Groups A and B had repeat measurements at six, 12 and 24 weeks. Group C had repeat measurements at 24 weeks.

Dependent Variables

Fasting serum triglyceride and cholesterol measurements were assessed with standard laboratory methods.

Independent Variables

Group A: Treatment by clinic nutritionist and physician with the National Heart and Lung Institute Type IV diet for six weeks, followed by diet plus clofibrate (500mg four times per day) for the remaining 18 weeks. The nutritionist conducted two group instructions at the start and individual meetings with participants every two to three weeks during the course of the study.
Group B: Same treatment by private physician
Group C: No intervention for 24 weeks, with subjects advised of abnormality
Drug adherence monitored by historical evaluation, pill counts and prescription refills.

Description of Actual Data Sample:

Initial N

4.000 employees were screened and 150 type IV subjects were identified as meeting inclusion criteria.

47 in Group A (34 men, 13 women)
53 in Group B (34 men, 19 women)
50 in Group C (35 men, 15 women).

Attrition (Final N)

144 completed the trial.

46 in Group A
48 in Group B
50 in Group C.

Age

Group A: Mean age 37.2±1.3 years
Group B: Mean age 37.5±1.2 years
Group C: Mean age 35.8±1.2 years.

Anthropometrics

No statistically significant differences between groups.

Location

Baltimore, Maryland.

Summary of Results:

Variables	Group A	Group B	Group C
Baseline Triglyeride (mg per dL)	406.9±29.5	381.3±41.3	344.1±23.2
Baseline Cholesterol (mg per dL)	232.4±6.6	232.2±7.1	229.5±5.2
Six-week Triglyceride (mg per dL)	200.2±15.2, P<0.0005	222.3±23.4, P<0.0005	---
Six-week Cholesterol (mg per dL)	206.6±7.1, P<0.0005	216.7±8.3, P<0.0005	---
12-week Triglyceride (mg per dL)	157.6±23.2, P<0.0005	189.8±9.2, P<0.0005	---
12-week Cholesterol (mg per dL)	209.4±7.0, P<0.0005	217.4±6.6, P<0.01	---
24-week Triglyceride (mg per dL)	155.3±14.3, P<0.0005	224.8±16.1, P<0.0005	276.2±27.7, P<0.0005
24-week Cholesterol (mg per dL)	217.6±6.9, P<0.01	222.4±5.9, P<0.025	221.9±5.7, P<0.05

Other Findings

Group A mean fasting serum triglyceride of 407mg per dL declined 50% at six weeks, 61% at 12 weeks and was unchanged at 24 weeks (all P<0.0005)
Group B triglyceride decreased 42% at six weeks, 50% at 12 weeks, and 41% at 24 weeks (all P<0.0005)
Group C triglyceride decreased 20% at 24 weeks
Body weight decreased 8% in Group A and 4% in Group B at six weeks (P<0.0005) and was unchanged at 24 weeks
The maximum cholesterol decrease was 11% in Group A (P<0.0005).

Author Conclusion:

Type IV hyperlipoproteinemia can readily be identified in a working population and treatment by clinic or private physician will markedly lower fasting serum triglyceride values in apparently healthy type IV subjects for at least 24 weeks.

Funding Source:

Government:

US Public Health Service, NHLBI

Reviewer Comments:

Statistical analysis is not well described.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	???
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		???
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	???
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes