Study Design

Transcript

• 00:02<v Maria>My name is Maria Ciarlegio</v>
• 00:04and I'm a faculty member
• 00:05in the Department of Biostatistics
• 00:08at the Yale School of Public Health.
• 00:11In this video series,
• 00:12I will introduce the clinical research process
• 00:15to prepare you to collaborate with a statistician.
• 00:20In the second video,
• 00:21we'll discuss some study designs that are commonly used
• 00:25in clinical research.
• 00:27The study design used to answer your research questions
• 00:31is determined by the goal of the research
• 00:34and the feasibility of different designs,
• 00:36including the availability of resources.
• 00:39For example, a randomized clinical trial
• 00:42can require a good amount of administrative support
• 00:46in addition to the required clinical involvement.
• 00:50The first major distinction between study types
• 00:53is whether the study investigator decides
• 00:56if a participant receives the exposure
• 00:59or the intervention.
• 01:01Studies where the investigator assigns the exposure
• 01:05are experimental studies,
• 01:07and studies where the investigator
• 01:09does not assign the exposure are observational studies.
• 01:14In observational studies,
• 01:15the investigator observes or documents
• 01:18the presence of exposures and outcomes
• 01:21as they naturally occur in a population or a sample.
• 01:26There are both descriptive
• 01:28and analytical observational studies.
• 01:31A descriptive observational study
• 01:33is used to describe characteristics
• 01:36of a sample or population.
• 01:38There's no comparator group
• 01:40because the goal is simply to describe,
• 01:43not formally compare.
• 01:45For example, you can use a descriptive study
• 01:48to estimate the prevalence of a disease
• 01:50or report the results of a patient survey of symptoms.
• 01:55They can also be used to inform the design
• 01:57of a future comparative or analytical study.
• 02:00For example, you may not have a good estimate
• 02:03of baseline prevalence of disease
• 02:05for a future study testing a new treatment on that disease.
• 02:10A descriptive study can be used to estimate this value
• 02:14to help you design that future study.
• 02:16The first type of descriptive study is the case report,
• 02:20which usually describes a patient presenting with an unusual
• 02:25or complicated disease.
• 02:27When more than one patient is described,
• 02:30it becomes a case series.
• 02:32Case reports and case series are useful for defining cases,
• 02:36generating hypotheses about the causes of disease,
• 02:40or use in clinical education.
• 02:42Finally, descriptive cross-sectional studies
• 02:46collect information on the presence or the level of one
• 02:50or more characteristic at one point in time.
• 02:54Those characteristics can include risk factors
• 02:57or different exposures and outcomes,
• 03:00such as the presence of disease.
• 03:03If the goal is to report the distribution
• 03:05of one or more of the characteristics,
• 03:07then the cross-sectional study is descriptive.
• 03:11However, if the goal is to assess the relationship
• 03:13between say presence of an exposure
• 03:16and presence of disease,
• 03:18then the cross-sectional study is analytical.
• 03:21And we'll talk about analytical studies next.
• 03:24But the takeaway on cross-sectional studies
• 03:26is that they provide a snapshot
• 03:28of the frequency of disease and patient characteristics
• 03:32at one point in time.
• 03:35Analytical observational studies include a comparator
• 03:39or control group.
• 03:40The goal is to formally establish
• 03:43or quantify an association between exposures and outcomes.
• 03:47Again, the exposures are naturally determined
• 03:49in observational studies,
• 03:51unlike experimental studies
• 03:53where the investigator assigns exposure usually
• 03:56in the form of different treatments
• 03:58the temporal direction of the study determines
• 04:01the type of analytical observational study.
• 04:04If the study assesses exposures
• 04:06and outcomes at the same point in time,
• 04:08the study is cross-sectional.
• 04:10Analytical cross-sectional studies
• 04:12as opposed to descriptive cross-sectional studies, again,
• 04:16are used to assess the relationship
• 04:18between exposure and disease.
• 04:21An analytical cross-sectional study was conducted in Japan
• 04:26to assess the relationship
• 04:27between non-alcoholic fatty liver disease
• 04:30and periodontal disease.
• 04:32Magnetic resonance elastography
• 04:34was used to measure liver stiffness
• 04:36in these patients with NAFLD.
• 04:38They found an association between P. gingivalis positivity
• 04:42and number of periodontal pockets and liver stiffness.
• 04:46The idea here is that the investigators
• 04:49are looking at these patients at a snapshot in time,
• 04:52not over time, in this cross-sectional study.
• 04:56A cohort study follows patients forward in time
• 05:00for development or occurrence of the outcome.
• 05:04Investigators identify a group of patients
• 05:06without the outcome or disease of interest.
• 05:09And of these patients,
• 05:10some are exposed to an exposure of interest
• 05:13and some are unexposed.
• 05:16We follow the exposed and unexposed groups forward in time
• 05:20for development of the outcome.
• 05:22If we observe a higher incidence of the outcome
• 05:26in the exposed,
• 05:27then the exposure is associated
• 05:29with an increased risk of the outcome.
• 05:32A strength of the cohort study
• 05:34is that we know the exposure preceded the outcome.
• 05:37However, it's necessary to wait for the development
• 05:40of the outcome in prospective cohort studies.
• 05:43So they can be slow to conduct,
• 05:46especially in the case of rare outcomes.
• 05:50We often perform retrospective cohort studies.
• 05:54Here, the start of the study can occur
• 05:56after some patients have already developed
• 05:59the outcome of interest.
• 06:00Exposure status in the past
• 06:03is established using existing data, such as medical records.
• 06:08The goal is to establish a cohort of individuals
• 06:11without the outcome at a fixed point in the past
• 06:14and determine their exposure status at that point in time.
• 06:18Then determine if the patient
• 06:20subsequently develops the outcome.
• 06:23A limitation of retrospective cohort studies
• 06:26is that exposure status is not assessed
• 06:29by the study investigators
• 06:31because we often rely on medical records.
• 06:34So the desired exposure data may not be available.
• 06:38A case control study is an alternative design
• 06:42that begins by identifying a group of individuals
• 06:45with the outcome of interest.
• 06:47A similar control group without the outcome
• 06:50is also identified.
• 06:52Through chart reviews or interviews,
• 06:55the investigator then determines past exposure status.
• 06:59Unlike a retrospective cohort study
• 07:01that begins by identifying study participants
• 07:05based on the exposure and then assesses outcomes,
• 07:08the case control study begins by assessing the outcome
• 07:12and then determines past exposures.
• 07:15Case control studies are useful when studying rare outcomes
• 07:19or diseases with long latency.
• 07:21However, limitations include recall bias
• 07:24in recalling exposure,
• 07:26problems with selecting comparable controls,
• 07:29as well as some analytical issues.
• 07:33The other major arm of study designs
• 07:36are the experimental studies.
• 07:38The gold standard of evidence is the clinical trial,
• 07:41in particular, the randomized clinical trial.
• 07:44Here, the investigator randomly assigns participants
• 07:48to different exposures, for example,
• 07:50sorafenib or placebo in patients with advanced liver cancer.
• 07:55Usually each participant has an equal chance
• 07:58of being assigned to the two groups,
• 08:00although the allocation ratio
• 08:01does not have to be one-to-one.
• 08:04Here we have an example of a randomized control trial.
• 08:07This study randomly assigned patients
• 08:09with liver cancer to sorafenib or placebo.
• 08:14A traditional parallel group randomized clinical trial
• 08:17resembles a prospective cohort study,
• 08:20except for the important difference of randomization.
• 08:24Randomization is an important element
• 08:26of clinical trials
• 08:28because it protects against selection bias
• 08:30and should balance both known
• 08:32and unknown confounding factors between the exposure groups.
• 08:38Additional commonly used randomized trial designs
• 08:41include crossover designs, factorial designs,
• 08:45and cluster randomized clinical trials.
• 08:49In non-randomized control trials,
• 08:51participants are assigned to different interventions
• 08:54without following a random procedure.
• 08:57For example, assignment may be made according
• 09:00to investigator preference.
• 09:02This design is susceptible to bias
• 09:04due to the potential differences
• 09:06in patient characteristics between the two groups.
• 09:10Another type of study is the systematic review.
• 09:13The goal here is to review
• 09:15and synthesize all available evidence
• 09:18on a specific research question.
• 09:20Systematic reviews are carried out according to
• 09:23a pre-specified protocol that defines the question,
• 09:27describes the scope of the review,
• 09:29and the criteria and methodology that will be used.
• 09:33Begin by specifying the review question,
• 09:36the population you're studying,
• 09:38the interventions or exposures of interest,
• 09:41outcomes of interest,
• 09:42and study designs that should be included in the review.
• 09:46Then you'll list the eligibility criteria
• 09:49for the studies to be included.
• 09:51For example, you may only want to include evidence
• 09:54from randomized control trials
• 09:56or large scale observational studies.
• 09:59You'll then search PubMed and other databases
• 10:03for articles or studies that meet these criteria.
• 10:07An important step is assessing the quality of the studies
• 10:11and critically assessing how well the studies were done.
• 10:14Any potential issues with the design may introduce bias,
• 10:18so it's important to critique the strengths and weaknesses
• 10:21of the evidence you've accumulated.
• 10:23At this stage,
• 10:24you can also comment on gaps in the evidence,
• 10:27such as patient populations not represented in the research.
• 10:31Then you extract the data or the study results
• 10:34that are summarized in the manuscripts
• 10:36and the supplemental materials.
• 10:37And a final step involves synthesizing the results,
• 10:40or combining and analyzing the results
• 10:43from multiple studies.
• 10:45This can be a qualitative synthesis
• 10:48in which you summarize
• 10:49how the research you found fit together,
• 10:52describe the strengths and the weaknesses
• 10:54of the body of evidence,
• 10:56identify gaps in areas of future research,
• 10:59or it can be a quantitative synthesis.
• 11:03Quantitative synthesis is usually in the form
• 11:06of a meta-analysis.
• 11:09A meta-analysis is an analytical way of formally combining
• 11:14or pooling results from different sources.
• 11:17In this study, the goal was to estimate the effect
• 11:20of antiviral therapy on liver stiffness
• 11:23in patients with hepatitis B at six months,
• 11:25one year, two years, three years,
• 11:28and five years after beginning treatment.
• 11:31This flow chart shows the process of study collection.
• 11:34In the end, 24 studies were included in the analysis.
• 11:39Typically, a forest plot,
• 11:41which is the graph shown here on the right,
• 11:43displays the point estimates
• 11:45and 95% confidence intervals from each study,
• 11:48along with the pooled estimate.
• 11:51At six months from the start of therapy,
• 11:53data pooled from eight studies
• 11:55with 968 patients showed a significant decline
• 11:59in liver stiffness by 2.21 kilopascals
• 12:03as compared to pre-treatment LSM.
• 12:07In this video, we discussed some commonly used designs
• 12:11in clinical research, including observational studies,
• 12:14experimental studies, and systematic reviews.
• 12:17The next video, which is the third video in this series,
• 12:21will discuss the data collection process and variable types.
• 12:25Understanding variable types will prepare us
• 12:28for the fourth video in this series
• 12:30on sample size determination.