Classifying Human Studies into Design Types Using Factors

December 19, 2011

ida.sim@ucsf.edu

CTSA Human Studies Database Projecthttp://hsdbwiki.org/

Study Design Typology Goal• Identify most parsimonious set of unambiguous

factors that when collected, will correctly classify any study on individual humans into a set of common study design types

• collection can be via manual review, or automated extraction from Clinical Trial Management Systems (e.g., Velos) or electronic IRB systems (e.g., ClickCommerce)

What the Classification Yields

• The high-level study types (in red) represent distinct approaches to human investigations that are each subject to a distinct set of biases and interpretive pitfalls (e.g.,selection bias, generalizability, etc.)• Additional Descriptors elaborate on secondary design and

analytic features that introduce or mitigate additional biases and interpretive pitfalls

• some Additional Descriptors apply only to some study design types

• The classification also groups studies for • discussing design considerations for how T0 research fits with

T1-3 research (e.g., subject selection for tissue specimens)• Particular types of administrative overview/IRB approval needed

(e.g., interventional, retrospective, etc.)

A study (see slide 8 for definition)

Is the study an original study, or a meta study (a study of other studies*)?

Original

No

Non-organismal Studies(organization studies, policy analyses,

device tests, etc)

Non-human Organism Study(rat, mouse, etc.)

Is the organism human?

Meta

Human Study

Is the human data at the individual level?

Yes No (data is aggregated)

No

Systematic Review (of summary-level data: human, non-human,

policy, etc.)

Ecologic Study(see next slide)

Are any of the entities that are enrolled, exposed, or observed in the study any of the following: an organism, some part of an organism, or a collection of organisms?

Yes

•in original studies, observations are acquired directly on or from the study participants (including individual participant-level data from databases, and participant-level meta-analysis) •in meta studies, observations are acquired from journal articles, abstracts, etc. reporting on other studies

Yes

Interviews, focus groups, ethnographic studies, etc.

Qualitative Studies

Does the study use primarily quantitative or qualitative methods?

qualitative quantitative

Does the investigator assign one or more interventions?

Individual-human study

Yes No

see next slides

Yes No

Does the investigator have a choice of interventions to assign participants to?

Single Group

Does investigator assign interventions to and analyze data only within a single study

participant?

Crossover

Yes No

N-of-1 Crossover

Interventional Studies

Is the main comparison across or within participants?

Within Across

Parallel Group

What is the main variable on which participant selection is based?

An outcome variable A predictor variable

Themselves A variable that is neither an outcome

nor a predictor

Cross-sectional Cohort

Are participants with the main outcome being compared to:

Other participants

Case Control

Observational Studies

Case Crossover

Yes No

Does the investigator have a choice of interventions to assign participants to?

Single Group

Does investigator assign interventions to and analyze data only within a single study

participant?

Crossover

Yes No

N-of-1 Crossover

Interventional Studies

Is the main comparison across or within participants?

Within Across

Parallel Group

Interventional study

Additional Descriptors N-of-1 Crossover Parallel Group Single Group, etc.

Comparative intent (superiority, non-inferiority, equivalence)

√ √ √ N/A

Sequence generation (random, non-random) √ √ √ N/A

Allocation concealment method (a to e) √ √ √ N/A

Assignment to study intervention (non-factorial, factorial)

√ √ √ N/A

Unit of allocation (individual, cluster) N/A √ √ N/A

Blinding/Masking (yes/no of each of:participant, investigator)

√ √ √ N/A

Study phase (0, 0/1, 1,1/2, 2, 2/3, 3, 4) √ √ √ √

Pooled data (yes, no) N/A √ √ √

What is the main variable on which participant selection is based?

An outcome variable[retrospective inference:

outcome → exposure]

A predictor variable[prospective inference: exposure → outcome]

Themselves

Case Crossover Cross-sectional Cohort

Are participants with the main outcome being compared to:

Other participants

Case Control

Observational study

Additional Descriptors Case Crossover Case Control Cross-sectional Cohort

Have outcomes occurred before the study start? (yes [historical], no [prospective])

N/A N/A N/A √

Are cases and controls (or exposed andunexposed) drawn from the same studycohort/sample? (yes = nested, no = non-nested [akadouble cohort for cohort studies])

N/A √ √ √

Matching (subsamples matched on covariates ornot)

N/A √ √ √

Sampling method (probability, non-probability) √ √ √ √

Pooled data (yes, no) √ √ √ √

Is the comparison group selected or identifiedbased on genetic relation? (yes, no)

N/A √ √ √

A variable that is neither an outcome nor a predictor

What is a [unitary] StudyA study has two orthogonal components: a sample - i.e., a specific set of participants (i.e.,

recruited/selected entities) drawn from a population or collection

an inferential approach - i.e., how observations are collected with respect to interventions/exposures and/or how inference is drawn [e.g., a historical cohort and a prospective cohort may have identical inferences but observations are collected differently]

A study is a unitary study if and only if it has a single defined intended or actual sample and a single defined inferential approach

A study is a hybrid study if it has more than one intended or actual sample and/or more than one inferential approach

The study design typology should be applied to each unitary study (i.e., each unitary study is one pass through the study design typology)

The Six Entities that Characterize a Study

1. Entity that is recruited/selected• e.g., humans, clinics, randomized trials, states, mice

2. Entity that is randomized [if applicable]• e.g., humans, rats, eyes

3. Entity that is subject to intervention(s)/exposure(s)

• e.g., humans, hospitals, schools, monkeys

4. Entity that is observed, i.e., on which observations are made

• e.g.,  humans, policies/strategies, organizations, randomized trials

5. Finest-grain entity that is/was available for analysis

• e.g., individual patient data, clinic-level averages, population mean, summary-level patient results from randomized trials

6. Entity about which conclusions are made e.g., humans, rats, policies (e.g., costs of), populations