2: Types of Studies1

2 In Chapter 2: 2.1 Surveys 2.2 Comparative Studies

2: Types of Studies3 Types of Studies SurveysSurveys: describe population characteristics  §2.1 Comparative studies:Comparative studies: determine relationships between variables  §2.2

2: Types of Studies4 2.1 Surveys Goal: describe population characteristics Normally based on a sample (or subset) of the population Types of samples –Probability sample (e.g., simple random sample) –Non-probability sample (e.g., convenience sample)

2: Types of Studies5

6 Sampling Probability samples use chance mechanisms to select individuals The most basic type of probability sample is the simple random sample (SRS) SRS ≡ a sample of size n selected so that all possible combinations of n individuals from the population are equally likely to comprise the sample

2: Types of Studies7 SRS Method 1.Identify each population member with the numbers 1, 2,..., N 2.Pick a random spot to enter Table A 3.Select n tuples, discarding inappropriate tuples Alternatively, use a random number generator (e.g., to generate n random numbers between 1 and Nwww.random.org Keep in mind: the objective of an SRS: every possible subset is equally likely!

2: Types of Studies8

9 Other Types of Probability Samples (More Advanced Methods) Stratified random sample: randomly sample strata (subsets) with the population Cluster sample: randomly sample clusters comprising varying numbers of observations Multistage sampling: randomly sample random samples in multiple stages

2: Types of Studies10 Cautions  Undercoverage: groups in the source population are left out or underrepresented sampling frame  Volunteer bias: self-selected participants (volunteers) are atypical population members  Nonresponse bias: a large percentage of individuals refuse to participate or cannot be contacted

2: Types of Studies11 §2.2 Comparative Studies Objective: to determine the relationship between an explanatory and response variable Experimental designs  assign subjects to treatment or exposure groups and compare outcomes Nonexperimental design  classified subjects in exposure groups (no intervention) and compare outcomes

2: Types of Studies12 Study Design Outlines

2: Types of Studies13 Women’s Health Initiative (WHI) Experimental Design The WHI study randomly assigned about half its subjects to a group that received hormone replacement therapy (HRT). The other half received an identical looking placebo. Subjects were followed for ~5 years to ascertain various health outcomes, including heart attacks, strokes, breast cancer and so on. Example of publication: Writing Group for the Women's Health Initiative Investigators. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA, 288(3),

2: Types of Studies14 Nurse’s Health Study (NHS) Nonexperimental Design This study classified individuals according to whether they received HRT Subjects were followed (ongoing) for various health outcomes, e.g., heart attacks, strokes, breast cancer and so on. Example of publication: Stampfer, M., Colditz, G., Willett, W., Manson, J., Rosner, B., Speizer, F., et al. (1991). Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. New England Journal of Medicine, 325(11),

2: Types of Studies15 Comparison of WHI and NHS Both the WHI and NHS analyzed relationships between HRT (explanatory variable) and various health outcomes (response variables) WHI  investigators assigned the exposure (HRT)  experimental NHS  investigators measured the exposure but did not assign it  nonexperimental (observational)

2: Types of Studies16 Let us focus on selected experimental design concepts and techniques Experimental designs provides a paradigm for nonexperimental designs.

2: Types of Studies17 Terminology Used in Experiments Subject ≡ an individual participating in the experiment Factor ≡ an explanatory variable being studied in an experiment Treatment ≡ a specific set of factors

2: Types of Studies18 Subjects, Factors, Treatments (Illustration)

2: Types of Studies19 Subjects = 100 individuals who participated in the study Factor A = Health education (active, passive) Factor B = Medication (Rx A, Rx B, or placebo) Treatments = the six specific combinations of factor A and factor B Subjects, Factors, Treatments, Example, cont.

2: Types of Studies20 Schematic Outline of Study Design

2: Types of Studies21 Randomized Controlled Trials (RCT) Randomized: chance assigns the exposure Controlled: the exposed group is compared to a non-exposed group (comparative study design) Blinded: observations are made without knowledge subjects’ exposure status

2: Types of Studies22 Randomization Randomization is the second principle of experimentation Randomization refers to the use of chance mechanisms to assign exposures / treatments Randomization balances lurking variables among comparison groups, mitigating confounding effects of lurking variables

2: Types of Studies23 Randomization - Example Source: JAMA 1994;271: (link is active)JAMA 1994;271: Explanatory variable: Nicotine or placebo patch 60 subjects (30 in each group) Response variable / outcome: Cessation of smoking (yes/no) Random Assignment Group 1 30 smokers Treatment 1 Nicotine Patch Compare Cessation rates Group 2 30 smokers Treatment 2 Placebo Patch

2: Types of Studies24 Randomization – Example Number subjects 01,…,60 Use Table A (or a random number generator) to select 30 two-tuples between 01 and 60 If you use Table A, arbitrarily select a different starting point each time For example, if we start in line 19, we see

2: Types of Studies25 Randomization, cont. We identify random two-tuples, e.g., 04, 24, 73, 87, etc. Random two-tuples greater than 60 are ignored The first three individuals in the treatment group are 01, 24, and 29 Keep selecting random two-tuples until you identify 30 unique individuals The remaining subjects are assigned to the control group

2: Types of Studies26 Controlled Trial “Controlled” means there is non-exposed control group A concurrent control group is essential You cannot judge the effects of an expose without a concurrent control group because: –Many factors contribute to a health outcome (so-called multi-causality; causal interdependence) –Conditions change on their own over time –The placebo (and related) effects

2: Types of Studies27 Blinding Blinding: the measurement of the response made without knowledge of treatment type Works by balancing measurement error and preventing observer bias Can occur at several levels: –Single blinding: subjects blinded –Double blinding: subjects and measurement- takers blinded –Triple blinding: subjects, measurement-takers, analysts blinded

2: Types of Studies28 Ethics of Experimental Studies Equipoise - balanced doubt; can’t knowingly expose subjects to harm or withhold benefit Informed consent – subjects must be aware of study objectives Beneficence – must provide overall benefit to society Justice – must be administrated justly Independent oversight (e.g., IRB)