Understanding the Hierarchy of Evidence in Scientific Research and Its Significance in Vaccine Epidemiology

In the realm of scientific research, evidence plays a pivotal role in shaping our understanding of the world. From medicine to social sciences, researchers follow a hierarchical structure of evidence to assess the reliability and strength of their findings. This hierarchy provides a systematic approach to discern the credibility of various types of studies and their potential impact on decision-making. In this blog post, we will explore the hierarchy of evidence, emphasizing its significance in epidemiology.

1. Meta-Analyses and Systematic Reviews: At the pinnacle of the evidence pyramid, we find meta-analyses and systematic reviews. These studies provide comprehensive evaluations by synthesizing multiple primary research studies on a specific topic. By combining data from various sources, researchers can draw more robust conclusions and gain a broader perspective on the subject matter. For example, researchers could access data from many studies on vaccine effectiveness and combine the data to better understand vaccine effectiveness in different settings, or with different populations.
2. Randomized Controlled Trials (RCTs): Considered the gold standard in experimental research, RCTs involve random allocation of participants into control and experimental groups. These trials test the efficacy of interventions, treatments, or preventive measures in a controlled environment. The randomization process helps minimize bias and allows researchers to establish cause-and-effect relationships with higher confidence. In vaccine research, this would be done depending on the vaccine being studied. If the new vaccine being studied has no existing analogue, then the experimental group gets the new vaccine and the control group gets an inert placebo. However, if the new vaccine has an existing analogue — like the measles vaccine — then the experimental group would get the new vaccine and the control group would get the existing vaccine. Under the second scenario, extensive evidence should exist that the new vaccine has a good probability of success. This is because ethical use of RCTs for research involves not harming the participants, or not allowing them to be unprotected against a serious illness like measles if the experimental vaccine has not yet shown evidence of working well.
3. Cohort Studies: Cohort studies involve following a group of individuals over a specific period. Researchers observe and collect data on various exposures and outcomes, providing insights into the natural progression of diseases or the impact of certain factors over time. Cohort studies can be prospective (looking forward in time) or retrospective (looking back in time), and allow the examination of potential associations or risk factors. In vaccine research, a cohort study would look at a population and examine outcomes in vaccinated, under-vaccinated, and unvaccinated people. However, there would be no allocation to who would be in what category of vaccination, making the analysis difficult. For example, if an unvaccinated group has less incidence of a vaccine-preventable disease, are there other factors at play? On the other hand, if a vaccinated group has more incidence of a vaccine-preventable group, do they have any characteristics that place them at higher risk for the vaccine? This last scenario has played out in studies of vaccine efficacy in healthcare workers, where healthcare workers are more likely to encounter infectious agents than the general population and are more likely to be vaccinated, explaining the observed effect of vaccination on infection or disease.
4. Case-Control Studies: In case-control studies, researchers compare individuals with a specific outcome (cases) to those without the outcome (controls). These studies are particularly useful when investigating rare diseases or outcomes with long latency periods. While they offer valuable insights into potential risk factors, case-control studies are prone to recall and selection biases, making careful interpretation necessary. These kinds of studies have been used for decades to understand epidemics. However, causation is difficult to definitively establish with these studies because of the biases mentioned previously.
5. Cross-Sectional Studies: Cross-sectional studies provide a snapshot of a population at a particular point in time. You may have heard of them referred to more as surveys than “cross-sectional studies.” Researchers collect data on both exposure and outcome variables simultaneously, allowing the examination of associations between variables. While these studies are relatively quick and cost-effective, they only provide a snapshot and cannot establish causation. Nevertheless, they provide some good signals that something may be happening that needs to be explored further. For example, the follow-up surveys given during the rollout of the COVID-19 vaccines helped identify possible adverse reactions, like allergic reactions, in some populations, or in other populations. These cross-sectional studies are a good jump-off point to further studies to understand what is going on.
6. Case Reports and Case Series: Case reports and case series describe the experiences of individual patients or small groups. These studies often highlight unique or rare clinical presentations, adverse events, or treatment outcomes. While they are valuable for generating hypotheses, they are considered low on the hierarchy due to their limited sample size and potential for bias. However, they are used as initial evidence to support the beginning of more advanced studies, or to identify groups who should be included in other studies. It was because of case reports of opportunistic infections in otherwise healthy people that in 1981, leading to the identification of the Human Immunodeficiency Virus (HIV) as the causative agent.

Understanding the hierarchy of evidence is crucial for researchers, policymakers, and healthcare professionals to make informed decisions. By recognizing the strengths and limitations of different study designs, we can assess the reliability and generalizability of research findings. Ultimately, the hierarchy of evidence promotes scientific rigor and helps build a solid foundation for evidence-based practice, ensuring that decisions are grounded in the most reliable and valid evidence available.