Evaluation design II

Question 1

RCTs

Answer 1

• Randomised cross-over trials
○ Exposed to diff treatments - randomise order of treatments - indvs act as own controls
• Parallel randomised control trials
- Randomly assigned to diff groups

Question 2

the basic experimental principle

Answer 2

• Intervention only diff between 2 groups

- Achieved by random assignment

Question 3

Pretest-posttest experimental design

Answer 3

• Essential components
○ Identify study popn and determine appropriate sample size for exp and control groups
○ Randomly assign to exp and control groups
○ Pre-test everyone with standardised instrument
○ Introduce IV (intervention) to exp group while withholding from control
○ Post-test both groups with same instrument and under same conditions as pretest
- Compare amount of change in DV for both exp and control groups
- Exp designs attempt to provide max control for threats to internal val

Question 4

Pretest-posttest experimental design research

Answer 4

Robbins et al. (2012)

Question 5

Robbins et al. (2012)

Answer 5

The primary purpose of the study was to determine whether girls in one school receiving nurse counseling plus an after-school physical activity club showed greater improvement in physical activity, cardiovascular fitness, and body composition than girls assigned to an attention control condition in another school (N = 69). Linear regressions controlling for baseline measures showed no statistically significant group differences, but the directionality of differences was consistent with greater intervention group improvement for minutes of moderate to vigorous physical activity/hour (t = 0.95, p = .35), cardiovascular fitness (t = 1.26, p = .22), body mass index (BMI; t = -1.47, p = .15), BMI z score (t = -1.19, p = .24), BMI percentile (t = -0.59, p = .56), percentage body fat (t = -0.86, p = .39), and waist circumference (t = -0.19, p = .85). Findings support testing with a larger sample

Question 6

RCT

Answer 6

see notes

Question 7

why randomise people to groups?

Answer 7

Ensure that any factors that may influence outcome balanced (evenly distributed) between intervention and control groups

Question 8

Threats to internal validity

Answer 8

• Bias
  ○ Selection
  ○ Perf
  ○ Detection
  ○ Attrition
- Random error

Question 9

Threats to internal validity research

Answer 9

Halperin et al. (2015)

Question 10

Halperin et al. (2015)

Answer 10

Internal validity refers to the degree of control exerted over potential confounding variables to reduce alternative explanations for the effects of various treatments. In exercise and sports-science research and routine testing, internal validity is commonly achieved by controlling variables such as exercise and warm-up protocols, prior training, nutritional intake before testing, ambient temperature, time of testing, hours of sleep, age, and gender. However, a number of other potential confounding variables often do not receive adequate attention in sports physiology and performance research. These confounding variables include instructions on how to perform the test, volume and frequency of verbal encouragement, knowledge of exercise endpoint, number and gender of observers in the room, influence of music played before and during testing, and the effects of mental fatigue on performance. In this review the authors discuss these variables in relation to common testing environments in exercise and sports science and present some recommendations with the goal of reducing possible threats to internal validity.

Question 11

Selection bias

Answer 11

• When indvs in intervention and control groups systematically diff on factor that may effect outcome thereby leading to systematic error in outcome
• E.g. older people in one group, more females - related to prevalence of activity
• Randomisation reduces selection bias so diffs in outcomes between 2 groups can be attributed to diff treatment of groups (intervention/control) and not to
1. Confounding factor
2. Effect modifier
○ Similar to confound
○ Affects outcome measure
○ E.g. older people in intervention - intervention related to age - reduced likelihood of change - reduced effectiveness of intervention - being modified by age
○ Systematically be biased between groups and modifies outcome
3. Chance

Question 12

Selection bias research

Answer 12

Bolzern et al. (2018)

Question 13

Bolzern et al. (2018)

Answer 13

○ Background
○ Cluster-randomised controlled trials require different methodology from individually randomised controlled trials and have unique vulnerabilities to bias. We aimed to compare selection bias between samples of these two types of trials published in four high-impact journals.
○ Methods
○ TheJAMAarchives and OVID Medline were searched by single selection by one of us (JB) for cluster-randomised and individually randomised controlled trials published in four journals (BMJ, The Lancet, JAMA, and The New England Journal of Medicine). Two of us (JB and NM) independently double-extracted data from the 20 most recently published trials of each type up to July 3, 2017. Fixed-effects forest plots were generated to show any imbalances in baseline mean participant age between trial arms for each trial. Pooled imbalance was calculated for each trial type. The characteristic of age was chosen because it is reported universally, in standard units (years).
○ Findings
○ For individually randomised controlled trials, age imbalance between trial arms was not statistically significant (0·005 years, 95% CI −0·026 to 0·035). For cluster-randomised controlled trials, age imbalance was ten times greater and was statistically significant (−0·050, −0·057 to −0·043).
○ Interpretation
- Randomisation distributes participant characteristics equally between trial arms except when baseline imbalances occur at random. When studies are pooled, such random imbalances cancel out to become negligible: if imbalance is not negligible across pooled trials, it indicates compromised randomisation or that selection bias has acted on the sample. The significant age imbalance in the cluster-randomised but not the individually randomised trials suggests that cluster-randomised trials are more vulnerable to selection bias. This imbalance might not affect trial outcomes since age in the control group was not substantially greater than in the intervention group. However, it indicates that selection bias can enter though the design of cluster-randomised controlled trials—possibly during the widespread practice of post-randomisation recruitment—and is therefore concerning. One limitation is that selection bias levels may be different in a more general sample of trials than one from four high-impact journals. Our method of examining selection bias has indicated that cluster-randomised controlled trials may require a more robust approach. We recommend taking steps to minimise selection bias in this type of trial.

Question 14

Confounding

Answer 14

• When a 3rd/’other’ variable influences the association between 2 other variables (intervention and outcome) and ‘confounds’ the results of the study
- Has to be associated with exposure variable (intervention/control) and the outcome/change in the outcome

see notes

Question 15

Confounding research

Answer 15

Fuller (2019)

Question 16

Fuller (2019)

Answer 16

It is sometimes thought that randomized study group allocation is uniquely proficient at producing comparison groups that are evenly balanced for all confounding causes. Philosophers have argued that in real randomized controlled trials this balance assumption typically fails. But is the balance assumption an important ideal? I run a thought experiment, the CONFOUND study, to answer this question. I then suggest a new account of causal inference in ideal and real comparative group studies that helps clarify the roles of confounding variables and randomization.

Question 17

Performance bias

Answer 17

• Insufficient adherence to study protocol by researchers/Ps
• Researchers may not deliver intervention consistently to all Ps and Ps may differ in how they adhere
- Over/underestimate intervention - researchers may treat people diff depending on which group they are in - deliver intervention in same way to all people

Question 18

Performance bias research

Answer 18

Gold et al. (2012)

Question 19

Gold et al. (2012)

Answer 19

○ Objective: Randomised controlled trials (RCTs) aim to provide unbiased estimates of treatment effects. However, the process of implementing trial procedures may have an impact on the performance of complex interventions that rely strongly on the intuition and confidence of therapists. We aimed to examine whether shifting effects over the recruitment period can be observed that might indicate such impact.
○ Method: Three RCTs investigating music therapy vs. standard care were included. The intervention was performed by experienced therapists and based on established methods. We examined outcomes of participants graphically, analysed cumulative effects and tested for differences between first vs. later participants. We tested for potential confounding population shifts through multiple regression models.
○ Results: Cumulative differences suggested trends over the recruitment period. Effect sizes tended to be less favourable among the first participants than later participants. In one study, effects even changed direction. Age, gender and baseline severity did not account for these shifting effects.
- Conclusion: Some trials of complex interventions have shifting effects over the recruitment period that cannot be explained by therapist experience or shifting demographics. Replication and further research should aim to find out which interventions and trial designs are most vulnerable to this new kind of performance bias.

Question 20

Detection bias

Answer 20

• Systematically diff outcome measures between groups
• Researchers can administer outcome measures diff between groups
• Ps receiving intervention they like may over report changes in behav
- Researchers that want intervention to work - encourage people more at follow up test rather than baseline to help prove the effectiveness - overexaggerate

Question 21

Detection bias research

Answer 21

Torgerson and Torgerson (2003)

Question 22

Torgerson and Torgerson (2003)

Answer 22

Reporting or detection bias occurs when researchers are more assiduous in their reporting of events in one group compared with the alternative. For example, if there were an evaluation of an intervention to reduce school exclusions, schools in the intervention group might under- or over-report exclusions compared with the control schools, when in fact there were no differences between the groups. This difference might occur because the ‘active’ group may be more assiduous in their data collection. For example, in the experimental schools minor exclusions such as for a day or for a lunch time, may have been reported when data on similar events in the control schools may not have been collected. Alternatively, the control schools could be more assiduous in reporting exclusions because of the possible demoralisation felt due to being randomised to act as a control. Reporting bias can be minimised if reporting is undertaken blind to treatment allocation, that is, the person who is measuring the outcomes does not know which group is the intervention. We accept, however, this is not always possible. Alternatively, event reporting can be ascertained from differential sources (e.g. participant and teacher and local authority), which should minimise the risk of detection bias.

Question 23

perf and detection bias

Answer 23

• Perf and detection bias can be avoided by blinding researchers and/or Ps to group allocation - double blind trial
- Often difficult in behavioural studies to blind Ps

Question 24

perf and detection bias research

Answer 24

Agouropoulos et al. (2014)

Question 25

Agouropoulos et al. (2014)

Answer 25

○ Objectives: To evaluate the effect of biannual fluoride varnish applications in preschool children as an adjunct to school-based oral health promotion and supervised tooth brushing with 1000 ppm fluoride toothpaste.
○ Methods: 424 preschool children, 2-5 year of age, from 10 different pre schools in Athens were invited to this double-blind randomized controlled trial and 328 children completed the 2-year programme. All children received oral health education with hygiene instructions twice yearly and attended supervised tooth brushing once daily. The test group was treated with fluoride varnish (0.9% diflurosilane) biannually while the control group had placebo applications. The primary endpoints were caries prevalence and increment; secondary outcomes were gingival health, mutans streptococci growth and salivary buffer capacity.
○ Results: The groups were balanced at baseline and no significant differences in caries prevalence or increment were displayed between the groups after 1 and 2 years, respectively. There was a reduced number of new pre-cavitated enamel lesions during the second year of the study (p = 0.05) but the decrease was not statistically significant. The secondary endpoints were unaffected by the varnish treatments.
○ Conclusions: Under the present conditions, biannual fluoride varnish applications in preschool children did not show significant caries-preventive benefits when provided as an adjunct to school-based supervised tooth brushing with 1000 ppm fluoride toothpaste.
- Clinical significance: In community based, caries prevention programmes, for high caries risk preschool children, a fluoride varnish may add little to caries prevention, when 1000 ppm fluoride toothpaste is used daily. (C) 2014 Elsevier Ltd. All rights reserved.

Question 26

Attrition bias

Answer 26

• Systematic diffs in no. drop outs from study between intervention and control groups
○ Often more in control if not getting anything
• Leads to systematic diffs in groups at follow up - not balanced
• Can be managed by intention to treat analysis methods
○ Analyse data on people still in study and keep everyone in who were lost at follow up
○ Just baseline measure = carry forward - assume the same
○ Midline test - 2 tests before outcome - did some but not outcome - last observation carried forward
- No. people randomised = no. people in analysis

Question 27

Attrition bias research

Answer 27

Hindmarch et al. (2015)

Question 28

Hindmarch et al. (2015)

Answer 28

○ Background: Failure to retain participants in randomised controlled trials and longitudinal studies can cause significant methodological problems. We report the recruitment and retention strategies of a randomised controlled trial to promote fire-related injury prevention in families with pre-school children attending children’s centres in disadvantaged areas in England.
○ Methods: Thirty-six children’s centres were cluster randomised into one of three arms of a 12-month fire-related injury prevention trial. Two arms delivered safety interventions and there was one control arm. Retention rates compared the numbers of participants responding to the 12-month questionnaire to the number recruited to the trial. Multivariable random effects logistic regression was used to explore factors independently associated with participant retention.
○ Results: The trial exceeded its required sample size through the use of multiple recruitment strategies. All children’s centres remained in the study, despite increased reorganisation. Parent retention was 68% at 12 months, ranging from 65% to 70% across trial arms and from 62% to 74% across trial sites. There was no significant difference in the rates of retention between trial arms (p = 0.58) or between trial sites (p = 0.16). Retention was significantly lower amongst mothers aged 16-25 years than older mothers [ adjusted odds ratio (AOR) 0.57, 95% CI 0.41, 0.78], those living in non-owner occupied accommodation than in owner occupied accommodation (AOR 0.53, 95% CI 0.38, 0.73) and those living in more disadvantaged areas (most versus least disadvantaged quintiles AOR 0.50, 95% CI 0.30, 0.82).
- Conclusions: Studies recruiting disadvantaged populations should measure and report attrition by socioeconomic factors to enable determination of the extent of attrition bias and estimation of its potential impact on findings. Where differential attrition is anticipated, consideration should be given to over-sampling during recruitment and targeted and more intensive strategies of participant retention in these sub-groups. In transient populations collection of multiple sources of contact information at recruitment and throughout the study may aid retention.

Question 29

Reporting of RCTs

Answer 29

see notes

Question 30

Reporting of RCTs research

Answer 30

Schuller et al. (2009)

Question 31

Schuller et al. (2009)

Answer 31

We developed a novel diagram to depict patient flow and outcomes in clinical trials. In contrast to flow diagrams such as the CONSORT chart, our diagram enables individual patient histories to be traced and depicts important patterns of treatment administration and outcomes, such as response and adverse events. Also, it is particularly useful for multimodal treatments or a sequence of different therapies where the CONSORT flow chart is less informative and can be confusing.

Question 32

Exercise as an intervention to reduce study-related fatigue among Uni students: 2-arm parallel randomised controlled trial (de Vries et al. 2016)

Answer 32

see notes

• Background
○ Aim to investigate to what extent exercise intervention effective in reducing indicators of study-related fatigue (emotional exhaustion, overall fatigue and need for recovery)
○ Effects of exercise of secondary outcomes (sleep quality, self-efficacy, physical fitness and cog functioning) also investigated
• Methods
○ Ps students with high levels of study-related fatigue, currently not exercising/receiving other psych/pharmacological treatments, and with no medical cause of fatigue
○ Randomly assigned to either 6-week ex intervention (low-intensity running 3x week, n=49) or wait list (no intervention, n=48)
○ All Ps measured before intervention (T0) and immediately after intervention (T1)
○ Exercisers also investigated 4 weeks (T2) and 12 weeks (T3) after intervention
• Results
○ Ps in exercise condition showed larger decrease in 2/3 indicators study-related fatigue (overall fatigue and need for recovery) as compared to controls
○ Sleep quality and some indicators of cog functioning improved more among exercisers than controls
○ No effects found for self-efficacy and physical fitness
○ Initial effects of ex intervention lasted at follow-up (T2 and 3)
○ At T3, 80% of Ps in ex condition still engaged in regular exercise and further enhancements seen for emotional exhaustion, overall fatigue and sleep quality
• Conclusions
○ Underline value of low-intensity ex for uni students with high levels of study-related fatigue
- Follow-up effects imply that intervention has potential to promote regular ex and accompanying beneficial effects in longer run

Question 33

hypothesis

Answer 33

• 1: intervention reduces study-related fatigue
• 2a: intervention improves sleep quality
• 2b: intervention improves sleep duration
• 2c: improves self-efficacy
• 2d: improves physical fitness
- 2e: improves cog functioning

Question 34

example RCT

Answer 34

see notes

Question 35

results

Answer 35

• Ps in exercise conditions showed larger decrease in 2 of 3 indicators of study-related fatigue (i.e. overall fatigue and need for recovery) as compared to controls
• Additionally, sleep quality and some indicators of cog functioning improved more among exercisers than controls
- No effects found for self-efficacy and physical fitness

Question 36

Fleckenstein et al. (2021)

Answer 36

○ Background Sleep-loss is a severe problem in night-shift workers. It causes fatigue and a decrease in awareness that may be counter-acted by exercise. This randomised controlled study in 22 university students investigated the effects of exercise on cognitive and physical performance following sleep deprivation.
○ Methods We were comparing a single bout of a 20-minutes circuit training to control in an experimental setting of overnight sleep loss. Outcomes included memory, cognitive tasks, and physical parameters. The occurrence of false memories was considered being the main outcome.
○ Results Exercise did not exert signicant effects on false memories (p = 0.456). We could detect a trend to signicanxe (p < 0.01) assessing cognitive dimensions, i.e. selective and sustained attention, and visual scanning speed. This revealed strong effects of exercise on attention (p = 0.091; Cohen’s d = 0.76; ∆14%), cognitive performance, performance speed, and perceived sleepiness (p = 0.008; d = 0.60; ∆2.4 cmVAS).
- Conclusions This study failed to show effects of exercise on memory function. Still, medium to strong effects on attention and consciousness can be considered clinically relevant. The results of this study encourage further research to determine its practicability and meaningfulness among night-shift workers.

Question 37

advantages of RCTs

Answer 37

• Because only thing that differs between intervention and control is ‘intervention’, means can be most confidence that any observed changes can be attributed to intervention and not any other factors
• Randomisation of Ps to test and control arms and concealment of allocation ensures allocation (selection) bias and confounding/unknown variables minimised
• RCTS regarded as having high internal val
• Nickson (2020) - Life in the Fast Lane
○ only type of study able to establish causation
○ ability to assign and administer treatment or intervention in a precise, controlled way.
○ decreases selection bias and minimises confounding due to unequal distribution in a chosen population
○ measurements can be chosen precisely making it easier to make observations consistently (especially parametric data)
○ blinding is easier improving credibility
○ decreasing patient or observer bias
○ controlling of group allocations enhances similarity of baseline features so it is easier to form basis for statistical hypothesis
○ can make trial large -> may detect clinically relevant conclusions
○ can have subgroup analysis enhancing usefulness for clinical practice
- a successful RCT with conclusive or inconclusive results is eminently publishable.

Question 38

disadvantages of RCTs

Answer 38

• Expensive and time consuming
• High dropout when intervention has undesirable side-effects/little incentive to stay in control
• Ethical consideration may mean that research Q cannot be investigated using RCT design
○ Can’t tell people not to exercise or to smoke for example
• Prior knowledge required for sample size calculation - level of improvement that is clinically meaningful
○ Expected variation of improvement in sample
○ May have to do pilot studies if no prior research
• Problems with generalisability (Ps that volunteer to P might not be representative of popn being studied) - low external val
○ Strict exclusion criteria
• Nickson (2020) - Life in the Fast Lane
○ high cost
○ increased time (clinical practice may move on while the study is being performed)
○ logistically challenging (e.g. difficulty organising/supervising multiple sites & locations)
○ results may not always mimic real life treatment situation (e.g. inclusion / exclusion criteria; highly controlled setting)
○ risk of choosing treatments or subjects whose consent is not valid or unethical treatment is involved
○ is a small trial has very stringent parameters -> type II errors decreased at the expense of applicability for a chosen population
○ practice misalignment can occur
- knowledge translation into clinical practice does not always occur

Question 39

medical research council

Answer 39

• Compare new treatment against current treatment
• See if safe and effective
• Variety of settings
• Randomly allocated to treatments - compare groups of indvs - chance to determine which groups - computer generated lists
• Want to make sure mix of people in each group roughly the same - make fair comparison
• Randomisation best and only reliable way of making comparison
• Make sure confounds even in diff groups
- Patients receive best possible standard treatment

Question 40

CRCT

Answer 40

Differ by the unit of randomisation

Question 41

What is a cluster RCT?

Answer 41

• Unit of randomisation not indvs but clusters of indvs on naturally occurring groups, e.g. schools/unis, households, hospital/geographical areas
• Clusters of people randomly allocated to intervention and control groups
• Mainly used when target of intervention cluster/when not feasible to prevent contamination in indv RCTs
- Control group behave like intervention because they learnt something/become aware about intervention - e.g. something that happens at community level

see notes

Question 42

What is a cluster RCT? research

Answer 42

Pfammatter et al. (2020)

Avitsland et al. (2020)

Question 43

Pfammatter et al. (2020)

Answer 43

○ Background: Cardiovascular disease (CVD) remains the leading cause of death globally. Seven health factors are associated with ideal cardiovascular health: being a non-smoker; not overweight; physically active; having a healthy diet; and normal blood pressure; fasting plasma glucose and cholesterol. Whereas approximately half of U.S. youth have ideal levels in at least 5 of the 7 components of cardiovascular health, this proportion falls to 16% by adulthood.
○ Objective: We will evaluate whether the NUYou cardiovascular mHealth intervention is more effective than an active comparator to promote cardiovascular health during the transition to young adulthood.
○ Methods: 302 incoming freshmen at a midwest university will be cluster randomized by dormitory into one of two mHealth intervention groups: 1) Cardiovascular Health (CVH), addressing behaviors related to CVD risk; or 2) Whole Health (WH), addressing behaviors unrelated to CVD. Both groups will receive smartphone applications, co-designed with students to help them manage time, interact with other participants via social media, and report health behaviors weekly. The CVH group will also have self-monitoring features to track their risk behaviors. Cardiovascular health will be assessed at the beginning of freshman year and the end of freshman and sophomore years. Linear mixed models will be used to compare groups on a composite of the seven cardiovascular-related health factors.
- Significance: This is the first entirely technology-mediated multiple health behavior change intervention delivered to college students to promote cardiovascular health. Findings will inform the potential for primordial prevention in young adulthood.

Question 44

Avitsland et al. (2020)

Answer 44

○ Purpose: To investigate the effects of two school-based physical activity interventions on mental health in Norwegian adolescents.
○ Methods: Students from 29 lower secondary schools in Norway (n = 2084; 14-15 years; 49% female) were cluster-randomized into either a control group or one of two intervention groups (M1 and M2). Two interventions based on different theoretical frameworks aimed to increase physical activity in school by approximately 120 min per week, throughout a 29-week intervention period. M1 consisted of 30 min physically active learning, 30 min physical activity and one 60 min physical education lesson. M2 consisted of one physical education lesson and one physical activity lesson, both focusing on facilitating students’ interest, responsibility and social relationships. The self-report version of the Strengths and Difficulties Questionnaire was used to assess mental health. Physical activity was measured by accelerometry. Linear mixed effects models were used to examine the effects of the interventions.
○ Results: No effects were found for the overall study population. Interaction effects warranted subgroup analyses: M1 showed favorable results in the subgroup with the highest levels of psychological difficulties at baseline (b = -2.9;-5.73 to -0.07; p = .045) and in the immigrant subgroup (b = -1.6;-3.53 to 0.27; p = .093). M2 showed favorable results in the immigrant subgroup (b = -2.1; -4.36 to 0.21; p = .075).
- Conclusions: The two interventions did not improve mental health in the full study population. However, results indicated beneficial effects among immigrants and those with poor mental health at baseline. More research is needed due to missing values and the results should therefore be interpreted with caution.

Question 45

Promoting PA in older people in general practice: ProAct65+ cluster RCT

Answer 45

• Aim
○ To eval 2 exercise programmes promoting PA among older people
• Design
○ 3 arm, parallel design cluster RCT involving 1256 people aged 65+ recruited from 43 general practices in London, Nottingham and Derby
• Interventions
- Otago Exercise Programme (OEP - ankle and hand held weights supervised by peer volunteers) and weekly ex group (held in local venues - more detailed instructions run by experts - FaME) - ran for 24 weeks

Question 46

Consort diagram (Illiffe et al.)

Answer 46

see notes

• Stratified based on location - randomised within location - ensure not imbalance between intervention and control
• Far fewer people available for analysis than at start
○ Assume that those that were lost had same second measurement as baseline - treat as worse case scenario
- May introduce bias

Question 47

results

Answer 47

• The FaME programme increase self-reported PA 12 months post-intervention and reduced falls
• Uptake to intervention low - reduces overall effectiveness
- No effect of OEP programme compared with usual care

Question 48

advantages of CRCTs

Answer 48

• Evaluates the real-world effectiveness of an intervention as opposed to efficacy - focus is on understanding effects of intervention in pragmatic, real-world setting
• Provide alternative method for assessing effectiveness of interventions in settings where randomisation at indv level inappropriate/impossible
• Often most appropriate experimental design when risk of contamination if indvs randomised
• Velengtas et al. (2012)
○ The cluster RCT evaluates the real-world effectiveness of an intervention as opposed to efficacy. It may be useful for comparative effectiveness research because the focus is on understanding the effects of an intervention in a pragmatic, real-world setting.
- It provides an alternative methodology for assessing the effectiveness of therapies in settings where randomization at the individual level is inappropriate or impossible

Question 49

disadvantages of CRCTS

Answer 49

• Complex and expensive
• Cluster RCT design requires greater no. people compared to indv RCT designs because people within clusters may be more similar to each other than would be expected by chance (intracluster correlation) - e.g. clusters of uni classes - sports science students more similar to each other than to English students
• Getting balanced groups more difficult, therefore internal val reduced
• Analysis complex - 2 sources variability must be taken into account in analyses: variation between indvs within groups and variation of indvs between groups
• Velengtas et al. (2012)
○ The complex design of the cluster RCT requires adequate understanding, implementation, and proper reporting by researchers. In order to ensure accurate interpretation of cluster RCTs by readers, the Consolidated Standards of Reporting Trials (CONSORT) statement for reporting individually randomized trials was extended to include guidelines for reporting of cluster RCTs in 2004.1,8
○ The cluster RCT design requires a greater number of patients compared to individual RCT designs because of intracluster correlation.1 In order to obtain statistical power equivalent to that of individual randomization designs, nonstandard sample size approaches must be applied to avoid statistically underpowered studies (eg, inflation using a calculated intracluster correlation coefficient).2,9
- Autonomous patient decision-making can be jeopardized in cluster designs, as patients may not have access to treatments or procedures available only at other locations. Informed consent, then, represents an especially complex question in cluster RCTs. Cluster designs should not be used in circumstances where the same information could be reliably obtained through individual randomization

Question 50

Iliffe et al. (2015)

Answer 50

• Background
○ PA levels low in older age groups
• Aim
○ Evaluate 2 ex programmes promoting PA among older people
• Design and setting
○ Pragmatic 3-arm, parallel-design cluster RCT involving 1256 people 65+ recruited from 43 general practices in London, Nottingham and Derby
• Method
○ Practices randomised to class-based Falls Management Exercise programme (FaME), home-based Otago Ex Programme (OEP), or usual care
○ Primary outcome was proportion reaching recommended PA target 12 months post-intervention
○ Secondary outcomes inc. falls, quality of life, balance confidence and costs
• Results
○ 49% of FaME Ps reached PA target compared with 38% usual care
○ Diffs between FaME and usual care persisted 24 months after intervention
○ No sig diff comparing those in OEP (43% reaching target at 12 months) and usual-care arms
○ Ps in FaME arm added around 12 mins of moderate-vigorous PA per day to baseline level - also had sig lower rate of falls
○ Balance confidence sig improved in both interventions
○ Mean cost per extra person achieving PA target £1740
○ Attrition and rates of adverse similar
• Conclusion
○ FaME programme increases self-reported PA for at least 12 months post-intervention and reduces falls in people 65+, but uptake low
- No stat sig diff in reaching target/in falls, between OEP and usual-care arms

Question 51

ScHARR library

Answer 51

• Difficult to treat people in diff group in diff way
• People within clusters more similar to each other than would expect by chance
• Blocked randomisation
• Randomisation done in advance - know which group in before treatment starts
• Often difficult to blind patients
• Assessors can be blind to treatment
• Often is recruitment bias - may be able to spot which group Ps are in so may recruit certain Ps
• Not sure whether groups balanced
• Recruit first then randomise
• Separate group decide whether P eligible before do trial
• Few clusters
○ Stratified sampling
- Harder to control for indv variation

Question 52

KCEfgov

Answer 52

• Pre-existing groups 
• E.g. schools, geographical areas 
• Intervention aimed at a cluster 
• May do it due to contamination - may need to separate groups 
• Logistically/ethically to separate indvs 
• Need larger sample size
• Makes the study more complex
• Can introduce more bias 
- Normal RCT are preferable