1.4 - Hypotheses in Epidemiology, Designs and Populations

Epidemiologic Hypothesis

An epidemiologic hypothesis is a testable statement of a putative relationship between an exposure and disease. The hypothesis should be:

  • Clear
  • Testable or resolvable
  • State the relationship between exposure and disease
  • Limited in scope
  • Not inconsistent with known facts
  • Supported by literature, theory, references

Look at the objectives in the following abstracts. Do these objectives meet the criteria for sound epidemiologic hypotheses?

Abstract 1: Robert J. Valuck and J. Mark Ruscin. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. Journal of Clinical Epidemiology 57 (2004) 422–428.

Objective: Acid-suppressant drugs are commonly prescribed for elderly patients, a population in which vitamin B12 deficiency is a common disorder. The purpose of this study was to examine the possible association between use of prescription histamine H-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) and vitamin B12 deficiency in older adults.

Study Design and Setting: This was a case–control study in a University-based geriatric primary care setting. Among patients aged 65 years or older with documented serum vitamin B12 studies between 1990 and 1997, 53 vitamin B12-deficient cases were compared with 212 controls for past or current use of prescription H2RA/PPI according to information in subjects’ medical records.

Results: Controlling for age, gender, multivitamin use, and Helicobacter pylori infection, chronic (12 months) current use of H2RA/PPI was associated with a significantly increased risk of vitamin B12 deficiency (OR 4.45; 95% CI 1.47–13.34). No association was found between past or short-term current use of H2RA/PPI and vitamin B12 deficiency.

Conclusion: These findings support an association between chronic use of H2RA/PPI by older adults and development of vitaminB12 deficiency. Additional studies are needed to confirm these findings.

Abstract 2: Risk factors of gastroesophageal reflux disease methodology and first epidemiological results of the ProGERD study. M. Kulig, M. Nocon, M. Vieth, A. Leodolter, D. Jaspersen, J. Labenz, W. Meyer-Sabellek, M. Stolte, T. Lind, P. Malfertheiner and S. N. Willich J Clin Epi. June 2004, Volume 57, Issue 6, Pages 580-589

Objective: We describe the design and report the first results of the Progression of Gastroesophageal Reflux Disease (ProGERD) study, to our knowledge the largest prospective study of GERD patients.

Study Design and Setting: Patients were recruited at 1,253 centers in German, Austria, and Switzerland. Following an assessment of medical history, all patients were endoscoped and received esomeprazole for 2 to 8 weeks before entering the 5-year observational phase.

Results: A total of 6,215 patients (53% male, age 54 14) were included. Of these patients, 46% reported at least daily symptoms, 15% were unable to work at least once during the prior year, and 71% had visited a physician due to reflux symptoms. Barrett’s esophagus (BE) was found in 11% of our GERD patients. In polychotomous regression analysis, the main factors related to the occurrence of the three GERD subgroups (nonerosive, erosive disease, and BE) were age, gender, duration of GERD, body mass index (BMI), smoking, and previous PPI use. Factors associated with longer disease duration were increasing age, male gender, BMI, increasing symptom severity, presence of erosive GERD or BE, positive family history, and smoking.

2004 Conclusion: The findings indicate that GERD is a great burden for patients, and has significant socioeconomic implications. The long term follow-up period with further endoscopic and histologic evaluations, will help further our understanding of the natural course of the disease.

Update:

Labenz J, Nocon M, Lind T, Leodolter A, Jaspersen D, Meyer-Sabellek W, Stolte M, Vieth M, Willich SN, Malfertheiner P. "Prospective Follow-Up Data from the ProGERD Study Suggest that GERD Is Not a Categorial Disease." Am J Gastroenterol. 2006 Nov;101(11):2457-62. Epub 2006 Oct 4.

Results: "After 2 yr, 25% of patients who had NERD at baseline progressed to LA A/B and 0.6% to LA C/D; 1.6% of patients who had LA A/B progressed to LA C/D and 61% regressed to NERD; 42% of patients who had LA C/D regressed to LA A/B and 50% regressed to NERD (all figures exclude patients with confirmed BE at baseline). At 2 yr, 22% of patients had been off medication for at least 3 months. Patients with ERD-LA grade C/D were at greatest risk of developing BE: 5.8% compared with 1.4% for ERD-LA grade A/B and 0.5% for NERD."

2006 Conclusion: GERD does not seem to be a categorial disease. Progression and regression between grades was observed in this large cohort of patients under routine clinical care.

Both studies met their objectives yielding a suggestion of association between use of prescription histamine H-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) and vitamin B12 deficiency in older adults from the first study and description of GERD from the second that showed both progression and regression between grades as common occurrences.

Hierarchy of Epidemiologic Study Designs in the Demonstration of Causality/Prevention

The design of a study contributes to the strength of its findings. Below are types of studies, in order of increased strength for testing the relevant hypothesis.We will study some of these designs further later in this course.

Causation Hypothesis

  • Case Study (describing one person with the condition, a case)
  • Case Series (series of cases)
  • Ecological Study (analysis of group statistics..for example, comparing rates of disease between two countries)
  • Cross-Sectional Study (assessing individuals at one time, such as a survey)
  • Case-Control Study (studying those with the condition vs. those without)
  • Cohort Study (following subjects over time to study the initiation and progression of a condition)

Interventional Hypothesis

  • Case Study
  • Case Series
  • Ecological Study
  • Cross-Sectional Study
  • Case-Control Study
  • Cohort Study
  • Quasi-experimental

Notice the difference is the possibility of a quasi-experimental study when considering whether or not an intervention is effective.

Defining Populations

Target Population
Population to which inferences from the study are to be made
Study Population
Population from which study subjects (cases and non-cases are selected)
Sample
Subjects (cases and noncases that provide data to the study).

A target population may be defined by geography, demography, health status, or some other factor. The animation below shows these terms applied to a study in Pennsylvania. Click on the map below:

Target Population - Population to which inferences from the study are to be made.
Study Population - Population from which study subjects (cases and non-cases) are selected; in the animation, only cases were shown
Sample - Subjects drawn from the study population (cases and noncases that provide data to the study).

In the animation, the sampled cases all came from eastern and central PA. Can we draw inference to the entire 12 million population of PA from these results? We should consider whether the sample was a result of random selection among all 15 PA cases or if some bias entered the sample selection process. Obviously the method for selecting the sample can greatly influence the study results.

Now that you have completed reading the Lesson 1 Notes, go back to Canvas to complete the Week 1 assignments. (One assignment is to apply the terminology of the Epidemiologic Triad to an infectious disease, novel H1N1.)