Study design issues

Biological specimens or measurements collected by population researchers are generally associated with characteristics or behaviors of interest. Biomarkers can be used to measure health status and behaviors, or to validate a particular health condition reported by a study respondent.

What is the research hypothesis to be tested, and how will biomarkers contribute to the assessment?

The researcher first must decide how a biomarker will assist in addressing the research hypothesis or policy question. Examples include assessing:

how prevalent a specific disease or asymptomatic condition is in a population of interest
whether certain hormones influence reproductive or aging outcomes
what the prevalence of certain micronutrient deficiencies is in a population-based sample
what social behaviors are associated with infection risk and transmission
whether the reported use of tobacco is consistent with urinary cotinine measures
what patterns of spread of infectious disease occur in a population
whether a population has been or is exposed to certain environmental hazards (e.g., lead or pesticides)

What should be measured?

A biological assessment may assist in determining whether a health condition exists, it may provide information about exposure to and existence of infection, or it may confirm behaviors. Determining which of these are important to the research question is the first step. At the same time, the researcher must determine whether there is an assessment available and whether it is feasible and ethical to make such an assessment. Consulting with an expert about the latest biomarker assessments on the pertinent topic and getting recommendations about possible laboratory collaborations is critical before including collection of biomarkers in population research.

What are the sample size considerations for biomarker assessment?

As with other exposures of interest, the prevalence of a particular disease state or health condition will need to be considered when determining the number of participants to be recruited. Similarly, if the study is examining the occurrence of incident cases over a specified time period, the minimum sample size to measure change will have to be considered. Involving a statistician in determining minimum sample sizes will be important when biomarkers are collected because of the costs associated with this addition to the protocol.

How much will it cost?

The collection of biomarkers in a population study can add a significant cost to the project. It is critical that the researcher consider the following when developing cost estimates:

collection materials (collection tubes, swabs, gloves, ice packs, coolers, storage tubes, storage boxes)
hiring staff with specialized skills
staff training (collection protocols, Universal Precautions, ethical and consent issues)
transporting specimens (cold chain)
laboratory assay
biohazard waste disposal
long-term storage (freezers, freezer rack systems, backup generators, alarm systems)
staff and facilities for follow-up counseling or treatment
locating participants for follow-up and/or informing regular caregivers
providing treatment regimen to diseased participants

What biomarkers and health assessment measures have been used in population research?

The following list is not exhaustive, but provides some ideas about health measures that have been collected by population research projects.

micronutrient deficiencies — vitamin A, iron/anemia, iodine, zinc, folate
infections — sexually transmitted (syphilis, gonorrhea, trichomoniasis, chlamydia, HPV, HIV/AIDS, genital herpes), bacterial vaginosis, tuberculosis, hepatitis C, encephalitis
tropical diseases and parasites — malaria, dengue fever, trypanosomiasis, schistosomiasis, leishmaniasis, onchocerciasis, Chagas disease, hookworm, other intestinal parasites
vaccine-preventable diseases — polio, tetanus, measles, rubella, mumps, pertussis
markers of inflammatory response — cytokines, C-reactive protein
hormones — pregnancy, endocrine function, androgens, estrogens, thyroid, stress-related (cortisol, corticotropin releasing hormone, epinephrine, norepinephrine)
substance use — tobacco/cotinine, cocaine, marijuana/THC, opiates
environmental exposures — lead, organochlorines
radiology, ultrasound, and pathology — bone mass, brain imaging, pregnancy status and fetal growth, tissue assessment, placental abnormalities
markers of cardiovascular and circulatory function — cholesterol, triglicerides, lipids
genetic markers — polymorphisms related to nutrition, cancer, aging
other health assessments — blood pressure, anthropometry (height and weight/body mass index, skinfold, bioimpediance), blood glucose levels, vision and hearing screening, physical activity monitoring