Question

Identify and explain the methodology of this study in different words.

Abstract Background: As the US population ages, there is an increasing need for evidence based, peer-led physical activity programs, particularly in ethnically diverse, low income senior centers where access is limited Methods/design: The Peer Empowerment Program 4 Physical Activity (PEP4PA) is a hybrid Type Il implementation- effectiveness trial that is a peer-led physical activity (PA) intervention based on the ecological model of behavior change The initial phase is a cluster randomized control trial randomized to either a peer-led PA intervention or usual center programming. After 18 months, the intervention sites are further randomized to continued support or no support for another 6 months. This study will be conducted at twelve senior centers in San Diego County in low income, diverse communities. In the intervention sites, 24 peer health coaches and 408 adults, aged 50 years and older, are invited to participate. Peer health coaches receive training and support and utilize a tablet computer for delivery and tracking. There are several levels of intervention. Individual components include pedometers, step goals, counseling, and feedback charts. Interpersonal components include group walks, group sharing and health tips, and monthly celebrations. Community components include review of PA resources, walkability audit, sustainability plan, and streetscape improvements. The primary outcome of interest is intensity and location of PA minutes per day, measured every 6 months by wrist and hip accelerometers and GPS devices. Secondary outcomes include blood pressure, physical, cognitive, and emotional functioning. Implementation measures include appropriateness & acceptability (perceived and actual fit), adoption & penetration (reach), fidelity (quantity&quality of intervention delivered), acceptability (satisfaction), costs, and sustainability Discussion: Using a peer led implementation strategy to deliver a multi-level community based PA program can enhance program adoption, implementation, and sustainment. Trial registration: ClinicalTrials.gov, USA (NCT02405325). Date of registration, March 20, 2015. This website also contains all items from the World Health Organization Trial Registration Data Set. Keywords: Peer led, Older adults, Randomized control trial, Walking, Cost-effectiveness, Low-income

Answer 1

Answer:

The methodology used in this study is Randomised control trial.

The randomised controlled trial (RCT) is considered to provide the most reliable evidence on the effectiveness of interventions because the processes used during the conduct of an RCT minimise the risk of confounding factors influencing the results.

WHAT IS A RANDOMISED CONTROLLED TRIAL?

An RCT is a type of study in which participants are randomly assigned to one of two or more clinical interventions. The RCT is the most scientifically rigorous method of hypothesis testing available,5 and is regarded as the gold standard trial for evaluating the effectiveness of interventions.6 The basic structure of an RCT is shown in fig 2.

Treatment A Outcomes Population Sample of interestpopulation Randomisation TreatmentB Outcomes

WHY A RANDOMISED CONTROLLED TRIAL?

The main purpose of random assignment is to prevent selection bias by distributing the characteristics of patients that may influence the outcome randomly between the groups, so that any difference in outcome can be explained only by the treatment.7 Thus random allocation makes it more likely that there will be balancing of baseline systematic differences between intervention groups with regard to known and unknown factors—such as age, sex, disease activity, and duration of disease—that may affect the outcome.

APPRAISING A RANDOMISED CONTROLLED TRIAL

When you are reading an RCT article, the answers to a few questions will help you decide whether you can trust the results of the study and whether you can apply the results to your patient or population. Issues to consider when reading an RCT may be condensed into three important areas8:

• the validity of the trial methodology;

• the magnitude and precision of the treatment effect;

• the applicability of the results to your patient or population.

A list of 10 questions that may be used for critical appraisal of an RCT in all three areas is given in box 1.9

Box 1: Questions to consider when assessing an RCT9

• Did the study ask a clearly focused question?

• Was the study an RCT and was it appropriately so?

• Were participants appropriately allocated to intervention and control groups?

• Were participants, staff, and study personnel blind to participants’ study groups?

• Were all the participants who entered the trial accounted for at its conclusion?

• Were participants in all groups followed up and data collected in the same way?

• Did the study have enough participants to minimise the play of chance?

• How are the results presented and what are the main results?

• How precise are the results?

• Were all important outcomes considered and can the results be applied to your local population?

ASSESSING THE VALIDITY OF TRIAL METHODOLOGY

Focused research question

It is important that research questions be clearly defined at the outset. The question should be focused on the problem of interest, and should be framed in such a way that even somebody who is not a specialist in the field would understand why the study was undertaken.

Randomisation

Randomisation refers to the process of assigning study participants to experimental or control groups at random such that each participant has an equal probability of being assigned to any given group.10 The main purpose of randomisation is to eliminate selection bias and balance known and unknown confounding factors in order to create a control group that is as similar as possible to the treatment group.

Methods for randomly assigning participants to groups, which limits bias, include the use of a table of random numbers and a computer program that generates random numbers. Methods of assignment that are prone to bias include alternating assignment or assignment by date of birth or hospital admission number.10

In very large clinical trials, simple randomisation may lead to a balance between groups in the number of patients allocated to each of the groups, and in patient characteristics. However, in “smaller” studies this may not be the case. Block randomisation and stratification are strategies that may be used to help ensure balance between groups in size and patient characteristics.11

Block randomisation

Block randomisation may be used to ensure a balance in the number of patients allocated to each of the groups in the trial. Participants are considered in blocks of, say, four at a time. Using a block size of four for two treatment arms (A and B) will lead to six possible arrangements of two As and two Bs (blocks):

AABB BBAA ABAB BABA ABBA BAAB

A random number sequence is used to select a particular block, which determines the allocation order for the first four subjects. In the same vein, treatment group is allocated to the next four patients in the order specified by the next randomly selected block.

Stratification

While randomisation may help remove selection bias, it does not always guarantee that the groups will be similar with regard to important patient characteristics.12 In many studies, important prognostic factors are known before the study. One way of trying to ensure that the groups are as identical as possible is to generate separate block randomisation lists for different combinations of prognostic factors. This method is called stratification or stratified block sampling. For example, in a trial of enteral nutrition in the induction of remission in active Crohn’s disease, potential stratification factors might be disease activity (paediatric Crohn’s disease activity index (PCDAI) ⩽25 v >25) and disease location (small bowel involvement v no small bowel involvement). A set of blocks could be generated for those patients who have PCDAI ⩽25 and have small bowel disease; those who have PCDAI ⩽25 and have no small bowel disease; those who have PCDAI >25 and have small bowel disease; and those who have PCDAI >25 and have no small bowel disease.

Allocation concealment

Allocation concealment is a technique that is used to help prevent selection bias by concealing the allocation sequence from those assigning participants to intervention groups, until the moment of assignment. The technique prevents researchers from consciously or unconsciously influencing which participants are assigned to a given intervention group. For instance, if the randomisation sequence shows that patient number 9 will receive treatment A, allocation concealment will remove the ability of researchers or other health care professionals from manoeuvring to place another patient in position 9.

In a recent observational study, Schulz et alshowed that in trials in which allocation was not concealed, estimates of treatment effect were exaggerated by about 41% compared with those that reported adequate allocation concealment.13

A common way for concealing allocation is to seal each individual assignment in an opaque envelope.10 However, this method may have disadvantages, and “distance” randomisation is generally preferred.

Distancerandomisation means that assignment sequence should be completely removed from those who make the assignments. The investigator, on recruiting a patient, telephones a central randomisation service which issues the treatment allocation.

Although an RCT should, in theory, eliminate selection bias, there are instances where bias can occur.

Youshould not assume that a trial methodology is valid merely because it is stated to be an RCT. Any selection bias in an RCT invalidates the study design and makes the results no more reliable than an observational study. As Torgesson and Roberts have suggested, the results of a supposed RCT which has had its randomisation compromised by, say, poor allocation concealment may be more damaging than an explicitly unrandomised study, as bias in the latter is acknowledged and the statistical analysis and subsequent interpretation might have taken this into account.

Blinding

There is always a risk in clinical trials that perceptions about the advantages of one treatment over another might influence outcomes, leading to biased results. This is particularly important when subjective outcome measures are being used. Patients who are aware that they are receiving what they believe to be an expensive new treatment may report being better than they really are. The judgement of a doctor who expects a particular treatment to be more effective than another may be clouded in favour of what he perceives to be the more effective treatment. When people analysing data know which treatment group was which, there can be the tendency to “overanalyse” the data for any minor differences that would support one treatment.

Knowledge of treatment received could also influence management of patients during the trial, and this can be a source of bias. For example, there could be the temptation for a doctor to give more care and attention during the study to patients receiving what he perceives to be the less effective treatment in order to compensate for perceived disadvantages.

To control for these biases,“blinding” may be undertaken. The term blinding (sometimes called masking) refers to the practice of preventing study participants, health care professionals, and those collecting and analysing data from knowing who is in the experimental group and who is in the control group, in order to avoid them being influenced by such knowledge.

It is important for authors of papers describing RCTs to state clearly whether participants, researchers, or data evaluators were or were not aware of assigned treatment.

In a study where participants do not know the details of the treatment but the researchers do, the term “single blind” is used. When both participants and data collectors (health care professionals, investigators) are kept ignorant of the assigned treatment, the term “double blind” is used. When, rarely, study participants, data collectors, and data evaluators such as statisticians are all blinded, the study is referred to as “triple blind”.5

Recent studies have shown that blinding of patients and health care professionals prevents bias. Trials that were not double blinded yielded larger estimates of treatment effects than trials in which authors reported double blinding (odds ratios exaggerated, on average, by 17%).17

It should be noted that, although blinding helps prevent bias, its effect in doing so is weaker than that of allocation concealment.

Moreover, unlike allocation concealment, blinding is not always appropriate or possible. For example, in a randomised controlled trial where one is comparing enteral nutrition with corticosteroids in the treatment of children with active Crohn’s disease, it may be impossible to blind participants and health care professionals to assigned intervention, although it may still be possible to blind those analysing the data, such as statisticians.

Intention to treat analysis

As stated earlier, the validity of an RCT depends greatly on the randomisation process. Randomisation ensures that known and unknown baseline confounding factors would balance out in the treatment and control groups. However, after randomisation, it is almost inevitable that some participants would not complete the study for whatever reason. Participants may deviate from the intended protocol because of misdiagnosis, non-compliance, or withdrawal. When such patients are excluded from the analysis, we can no longer be sure that important baseline prognostic factors in the two groups are similar. Thus the main rationale for random allocation is defeated, leading to potential bias.

To reduce this bias, results should be analysed on an “intention to treat” basis.

Intention to treat analysis is a strategy in the conduct and analysis of randomised controlled trials that ensures that all patients allocated to either the treatment or control groups are analysed together as representing that treatment arm whether or not they received the prescribed treatment or completed the study.

Intentionto treat introduces clinical reality into research by recognising that for several reasons, not all participants randomised will receive the intended treatment or complete the follow up.

According to the revised CONSORT statement for reporting RCTs, authors of papers should state clearly which participants are included in their analyses.

The sample size per group, or the denominator when proportions are being reported, should be provided for all summary information. The main results should be analysed on the basis of intention to treat. Where necessary, additional analyses restricted only to participants who fulfilled the intended protocol (per protocol analyses) may also be reported.

Power and sample size calculation

The statistical power of an RCT is the ability of the study to detect a difference between the groups when such a difference exists. The power of a study is determined by several factors, including the frequency of the outcome being studied, the magnitude of the effect, the study design, and the sample size.

Foran RCT to have a reasonable chance of answering the research question it addresses, the sample size must be large enough—that is, there must be enough participants in each group.

When the sample size of a study is too small, it may be impossible to detect any true differences in outcome between the groups. Such a study might be a waste of resources and potentially unethical. Frequently, however, small sized studies are published that claim no difference in outcome between groups without reporting the power of the studies. Researchers should ensure at the planning stage that there are enough participants to ensure that the study has a high probability of detecting as statistically significant the smallest effect that would be regarded as clinically important.