Health and Society Musculoskeletal Flashcards
Learning outcomes
Global Prevalence of Disability ?
Social Outcomes for disabled people in the UK ?
- Less likely to have as good qualifications
- Less likely to be employed
- More likely to rent social housing
- There more likely to feel lonley
Social Outcomes for disabled people in the UK ?
- Less likely to have as good qualifications
- Less likely to be employed
- More likely to rent social housing
- There more likely to feel lonely
Disabled people feel like they have poorer wellbeing.
- so less happy
-less worthwhile
- Lower life satisfaction
- more anxiety
Measuring disability ?
- Clinical assessments of a persons disability can help guide support and care needs.
- Activities of Daily Life is a typical measure of disability.
What are the 4 models of disability ?
- Medical
- Social
- Psychological
- International Classification of Functionality Disability and Health (ICF)
Describe the biomedical model of disease ?
Describe the sick role the patient adopts?
The deficit model of disability:
- is when we try to define a persons disability by the things they cannot do
Describe the social model of disability ?
Social model of disability:
- Much of physical and social environments are ‘abelist’ they prioritize and assume that everyone can do the same things.
- Is the idea that a persons disability is not do to them not being able to do something but instead is due to the environment not enabling them to carry out a task.
- Only having staircases is a classic example of excluding a person in a wheelchair from participating in that activity.
- Less about curing the condition and more about accommodating the patient and allowing them to do what they want.
What are some critiques of the social model of disability ?
- can reduced the lived experiences of impairment to environmental barriers. Some peoples situations will not be improved by changing that persons environment.
Describe the ICF (international classification of functional disability and health) ?
- This makes us realize that treating a patient with a disability requires a multidisciplinary team.
- You may need a social worker, an occupational health therapist ….
What are the 5 qualities of patient- centered care ?
Why do we need randomized control trials ?
What is evidence based medicine ?
Evidence-based medicine (EBM) refers to the application of the best available research to clinical care, which requires the integration of evidence with clinical expertise and patient values.
Transparency in research is about making research publicly available, so all evidence can be considered and ultimately inform clinical decision making.
EBM is based on three fundamental principles. First, there is a hierarchy of evidence based on study design— from approaches that are at lower risk of bias (e.g. rigorously conducted randomized controlled trials) to approaches that are at higher risk of bias (e.g. observational studies).
Second, informed clinical decision-making requires use of all best available evidence, usually from systematic reviews to avoid selection bias.
Third, evidence alone is never enough for clinical decision-making, and clinicians must also consider patient’s values and preferences.
PATIENTS ULTIMATELY WANT TO KNOW “WHAT TREATMENT IS BEST FOR ME?”
BUT EBM is not restricted to randomised trials and meta-analyses. It’s about finding the best evidence with which to answer our clinical questions.
What is a clinical trial ?
A planned experiment involving humans, designed to determine the most appropriate treatment of future patients with a given medical condition
Note: the above does not assume a control group, nor randomisation
Clinical trials are categorised into phases I to IV.
Phase III trial are RCTs with one or more experimental treatments being compared against a standard (control) treatment in which an attempt is made to draw a definite conclusion regarding benefit, or otherwise, of a new treatment compared to another
What is a randomized control trial ?
Describe the hierarchy of evidence ?
Today we are mainly thinking about RCTs – but we will compare to other study designs, and think about the strengths and limitations of these different approaches. In EBM we often refer to the ‘hierarchy of evidence’
Bottom of the pyramid is the weakest evidence - Expert opinion and case-series have a high risk of bias, non-experimental, reporting on observations in a limited group
no control, no direct comparisons, not enough evidence to replace current standard.
Comparative studies – testing against a control. Moving from observational to non-randomised, to randomised studies. RCT considered ‘gold standard’
Systematic reviews/Meta-analysis – synthesis of RCTs with homogenous results
What is a randomized control trial ?
The main focus of this lecture is on RCTs.
RCTs are an experiment in which participants are randomly allocated into groups
Simplest design is 2 arm - Intervention and control
One group is the “experimental group” and receives the intervention being evaluated (Group 1) , and the other is the “control group” and receives the placebo or conventional treatment (Group 2) .
Outcomes in the two groups are then compared
Majority ofphase III trialsarerandomised controlled trials(RCTs).
Randomisation - Often hear ‘it’s like flipping a coin or rolling a dice’ – we’ll talk about different methods of randomisation later, but the principle is to create randomly allocated groups which receive different experimental treatments
The main reason to randomise is to control for the things that might affect the outcome and create balanced groups: factors that are specific to the patients (age, gender, preferences, attitudes), and clinician preference/selection of patients. We refer to this as reducing bias..
What factors determine whether drug development can go ahead ?
Do the advantages outweigh the disadvantages of taking the medicine?
Does the medicine do the most good for the least harm for most people who will be taking it?
Are the side effects acceptable? A high level of side effects may be acceptable for a medicine used to treat a life threatening illness, for example, but not in one used for a common minor ailment. Ultimately, patients and their healthcare professionals have to weigh up the pros and cons of each medicine when deciding on the most appropriate treatment.
Describe the drug development pathway
Often think of clinical trials, and phases, in the context of being part of the drug development pathway. This is a process of learning and confirming – the critical path may not follow in a linear way, there can be a need for iteration and repeating of earlier phase studies.
The drug discovery process includes many types of research from lab, to animals to human participants.
The drug development pathway starts with pre-clinical work, forming the initial idea about how to target a drug to either treat or prevent disease. Many novel compounds will be synthesised and tested in the laboratory before choosing candidates to take forward to animal testing.
After the drug discovery phase, a series of in vitro and in vivo preclinical studies must be conducted before human testing can begin. Preclinical studies must provide detailed information on dosing and toxicity levels. Any adverse findings in the preclinical phase can lead to ‘No-Go’ to human testing.
Data is collected and submitted as an IND (investigational new drug) application to regulatory authority before clinical studies can begin, but only assesses short-term duration. Non-clinical work continues alongside clinical trials, to produce long term toxicology data.
Describe the phases of clinical trials ?
Once determined that a compound may have potential as a therapeutic drug, and safety determined in pre-clinical, a drug progresses to testing in humans – clinical trials. Must comply with GCP and Clinical Trials Regulations.
As we move through the phases, the number of participants required increases, as does the time to complete the study. Later phase studies will often be multi-centre trials to ensure that sufficient patients can be recruited in a reasonable timeframe.
Table presented here gives general aims of the different phases of clinical trials, but these are not strict definitions, phases may incorporate design aspects from other phases / overlap aims.
Remember Critical Path, may involve ‘learning and confirming’
Phase 1 – healthy volunteers, small numbers, see how tolerated. Dose escalation.
Phase II – first use in patients with the condition, initial efficacy (proof of concept – does the drug have the expected effect?). Safety and tolerability – determine what doses are possible, could be different safety profile if e.g. cellular pathways are different in those with disease.
Phase III – Large patient studies using the intended therapeutic dose. Aiming to show clinical and cost-effectiveness, often in comparison to the current ‘gold standard’ treatment
Phase IV – long-term safety and effectiveness. Post-marketing, often open-label/clinical use, ongoing pharmacovigilance.
You have to see whether that drug will be able to work in the real world ?
NB – clinical trials are NOT just drug trials, we investigate may types of experimental treatment including medical devices, psychological/behavioural therapies, exercise/lifestyle changes, provision of services/care.
Depending on where in the developmental pathway your intervention fits, determines many aspects of the design of your research.
Initial evidence is needed to show it has the potential to work – proof of concept
Exploratory studies – in a well defined population to get initial efficacy, does it work. Controlled studies- internal validity.
Definitive effectiveness studies (Phase III) – large number of participants, pragmatic/real-world delivery, usually include health economic evaluation – how much does it cost and is it worth it - cost-benefit analysis. Still controlled (internal validity) but as in real-world also consider external validity (generalizability)
It is also important to think about adoption of the new treatment into clinical practice, and there is much more emphasis on mixed methods studies which include evaluation of implementation strategies/process evaluation/patient and clinician perspectives of the intervention.
What is trail reporting ?
There has been a moving focus towards full and transparent reporting of clinical trials over the last 2 decades. The AllTrials campaign calls for all past and present clinical trials to be registered and their full methods and summary results reported. The Declaration of Helsinki, which is the World Medical Association’s statement of principles for medical research involving people, states that every investigator running a clinical trial should register it and report its results.
There are four levels of information in clinical trial reporting: (1)knowledge that a trial has been conducted, from a clinical trials register; (2)a brief summary of the trial’s results; (3)full details about the trial’s methods and results; (4)individual patient data from the trial.
The AllTrials campaign is concerned with the first three. There are now initiatives in many countries to work out how individual patient data can be shared with other researchers.
Pre 2000 attitude:
The feminist movement in the 1960s changed women’s status and life expectancy, encouraging menopausal therapy, especially in European countries, with the concept of “feminine forever”. Wilson’s book, published in 1966 (“feminine forever”), became a bestseller, with its claim that “menopause is a hormone deficiency disease, curable and totally preventable, just take estrogen”
Hormone replacement therapy (HRT) was presented as a therapy that could allow women to free themselves from the malediction of estrogen loss and conserve their femininity
- HRT was advertised as being able to help reduce CVD
- However trial evidence showed that HRT increased cardiovascular disease.
- The reason for the belief that HRT did help women was because most women taking the drug were more active which reduces CVD.
- The association was due to these factors not HRT.
- This highlights the importance of trial
Why are RCT not always the best option ?
Randomised controlled trials (RCTs) are considered the ideal approach for assessing the effectiveness of interventions. However, not all interventions can be assessed with an RCT, whereas for many interventions trials can be prohibitively expensive.
Observational studies can address some of these shortcomings, but the lack of researcher control over confounding variables and the difficulty in establishing causation mean that conclusions from studies using observational approaches are generally considered to be weaker.
Quasi-experimental study designs researchers are able to estimate causal effects using observational approaches. Interrupted time series (ITS) analysis is a useful quasi-experimental design with which to evaluate the longitudinal effects of interventions, through regression modelling
This design is particularly useful when “natural experiments” in real word settings occur—for example, when a health policy change comes into effect. However, it is not appropriate when trends are not (or cannot be transformed to be) linear, the intervention is introduced gradually or at more than one time point, there are external time varying effects
What are some alternative designs to randomized control trials ?
Alternative designs to RCTs are commonly reported, sometimes there are reasons why RCTs are impracticable, but there are limitations with these designs and the strength of evidence that is produced.
A case report is the description of the clinical course of one individual, which may include particular exposures, symptoms, signs, interventions or outcomes. A case report is the smallest publishable unit in the literature, whereas caseseries report aggregates individual cases in one publication. No control, no direct comparisons, not enough evidence to replace current standard.
Historical controls
Using data from ‘similar’ controls identified from the literature or at same site in the past
Literature controls from published results of similar trial
Consecutive controls treated over different periods, e.g. in the same hospital
Before / after design
the same participants are measured before and after an intervention (act as their own control)
Concurrent (non-randomised) controls – patients not receiving the intervention, but receiving the standard treatment in the same time period as the trial.
Why do we use randomized control trials ?
Bias is the systematic distortion of the estimated intervention effect away from the “truth”, caused by inadequacies in the design, conduct, or analysis of a trial.
There are different sorts of bias.
Selection bias - That is, the groups differ in measured or unmeasured baseline characteristics because of the way participants were selected or assigned. A strength of randomisation is that, if successful, it prevents selection bias in allocation of participants. This will also mean that the participants are not representative of the population of all possible participants.
Detection bias is the systematic distortion of the results by the person assessing the outcome. Blinding or masking outcome assessors may reduce the risk that knowledge of which intervention was received affects outcome measurement.
Performance bias refers to the systematic differences between groups in the care that is provided, or exposure to factors other than the intervention of interest. Blinding of study participants and staff may reduce the risk that knowledge of which intervention was received, rather than the intervention itself, affects outcomes. In other words, if people believe the new treatment is better, and they got the new treatment, they may report better outcomes, simply because it’s the ‘new’ treatment.
Blinding of this type is not always possible, for example when comparing open versus laparoscopic bowel surgery.
Why do we randomize the trial ?
In Phase III trials participants are generally randomised to receive the intervention or control treatment. So why randomise?
Randomisation fulfils several purposes – it eliminates systematic bias, so the differences in outcomes can then be attributed to the intervention.
Helps ensure balance across comparative groups for known and unknown baseline factors that may affect outcome
Randomised groups followed up over the same time
Differences in outcomes can then be attributed to the intervention.
As researchers we should be in a state of clinical “equipoise” by which we mean we have genuine uncertainty as to which of two interventions is clinically superior. Randomisation is important because clinicians may not themselves not be in a state of equipoise, by which we mean they may have decided that one treatment is better than another, and they may bias groups if it is their decision as to who receives which treatment. From an ethical perspective, a person is not deciding on which arm – there is a risk/benefit consideration, a new treatment may be more effective but may have more side effects.
What are cluster randomized control trials ?
Alternative to individually randomized trials is cluster RCT.
Cluster randomised trials (CRTs) involve randomisation of groups (clusters) of individuals to control or intervention conditions. The CRT design is commonly used to evaluate non-drug interventions, such as policy and service delivery interventions.
A study may have to be conducted as a CRT if an intervention is being performed not at individual level but at the level of whole regions or organisations. Examples of such situations are the restructuring of a hospital, the implementation of guidelines, or the introduction of a new form of care. The intervention cannot be withheld from any individual in the organisational unit for fear of contamination.
The formation of clusters decreases the effective sample size and thus the statistical power of CRT compared with individually randomised trials, because persons within an organisational unit resemble each other more strongly than persons from different organisational units.
The intracluster correlation coefficient (ICC) measures the degree to which observations (that is, outcome measurements from participants) in a cluster are correlated. You need to account for the ICC when designing and analysing these trials
Still parallel group – some clusters are intervention and some control
Example of a randomized control trial ?
This is a basic schematic of an RCT.
Patients are screened for eligibility – and patients with recurrent malignant glioma and who give informed consent are eligible for the study. The usual treatment at this stage is a combination of three drugs called PCV, but something better is needed. Another drug called temozolomide (Temodol) looks promising, but it has never been directly compared with PCV in this patient group. The trial will assess which treatment is more effective, and which is more acceptable to patients in terms of side-effects.
Patients are randomised to receive different types of chemotherapy – Temozolomide or combination chemo PCV, which is known to have significant side effects
Both groups are treated and receive usual regular follow-up
The primary outcome is overall survival, and this will be compared between the two treatment groups
Baseline factors in a randomized control trial need to be balanced.
What would happen if we had biased allocation ?
What might happen if doctors could choose who gets what treatment?
Well, doctors might try to get the result they think the researchers want, so select patients they think will do well. This bias would potentially exaggerate the measured effect of the intervention.
Conversely, clinicians might choose to give the new intervention to the patients who are most ill and this would dilute the measured effect of the intervention.
So there are a number of reasons (conscious or often, unconscious) that may introduce some systematic bias into the allocation and thereby invalidate results. As we will see later in this presentation, qualitative work embedded into the study design can help detect and unpick these biases.
Methods of allocation in a RCT ?
There are many ways in which you could approach randomisation, but inadequate methods can lead to unbalanced groups, and some methods are liable to subversion of allocation concealment
toss of a coin to allocate groups - this is liable to result in different sized groups, especially in small samples and is open to manipulation.
Other approaches, such as using the patient date of birth, and allocating patients to their treatment depending on whether their birthday is an odd or even number means allocation is not concealed, and so it open to bias.
Alternative allocation – as patients present, easy to change the order in which you see a patient
Odd/even DOB, better – you may end up with all having an odd DOB
Best method is for a randomisation list to be prepared – which determines the order in which participants will be allocated to arms of the study.
This should be prepared and stored confidentially by someone not involved in delivering and assessing the intervention.
Sealed envelopes - this approach can be manipulated by either opening envelopes in advance or through transillumination.
Central, independent randomisation is recommended.
What is allocation concealment ?
Allocation concealment means the person randomising the participant to the study does not know what the next treatment allocation will be. This is important as it protects against selection bias. The gold standard approach to ensure allocation concealment is to use a centralised service as this means the process cannot be subverted by the researchers or clinicians. However, this is dependent on resources and so is not always possible.
Other approaches to simple randomisation include using a sealed envelope approach, by which I mean using real envelopes with the next allocation noted on a sheet sealed in the envelope. The problem with this is that if an investigator is determined enough they can find out what is in the next allocation is – for example using a light box, and thus bias the study.
Concealing allocation protects against selection bias.
What is blinding in RCT ?
Blinding is a measure that can help reduce the potential for bias, we can blind participants and staff to which group participants are allocated to.
Sometimes blinding is not possible, for example when we are comparing high compression stockings to traditional bandaging in the treatment of venous leg ulcers or when we compare healing and complication rates in open and laparoscopic (keyhole) bowel surgery. The patients and investigators will know what treatment the patient was allocated to.
Blinding of outcome assessment may be possible, by which we mean the person collecting the outcome data does not know which group the participant was allocated to. In cases like the leg ulcer study the assessment of healing of the ulcer could be measured through a series of photographs, judged independently by clinical experts unaware of the treatment allocation. In the bowel surgery study a more objective outcome measure such as complication rates could be used.
Blinding the person assessing the outcome is helpful when the outcome measure could be influenced by the patient or investigators beliefs about the allocated treatment, for example whether a patient feels they have improved or not.
In drug studies you may have non-subjective measures such as conc. of drug in blood (PK sampling), in which case there may not be the same need to blind the study
Sample size in a RCT ?
At the trial design stage, it is important to have a good idea of how many individuals are needed to take part. For an RCT, we need to have a reasonable chance of answering the hypothesis, i.e. there must be sufficient numbers of participants in each group.
The sample size should be clearly described, justified and reproducible.
Effect Size and MCID ?
Large MCID leads to small sample size; while small MCID leads to large sample size Effect size corresponds to statistical significance, while MCID corresponds to clinical significance.
Statistical analysis and results interpretation ?
Statistical analysis and result interpretation of RCTs is an important concept when considering the quality of the study and results. Transparent reporting guidelines include a clear flow diagram of patient identification and recruitment, treatment allocation, completion of treatment/intervention and outcome measures, and inclusion on analysis.
RCTs suffer from two main weaknesses - non-compliance with the intervention or placebo and missing data. To try to address these problems, a statistical concept called Intention to treat analysis is employed when analysing data.
Intention to treat (ITT) analysis includes every participant who is randomised according to randomised treatment assignment, ignoring noncompliance, protocol deviations, withdrawal, and anything that happens after randomisation. * It maintains prognostic balance from the original randomisation. * Estimate of treatment effect is generally conservative.
In contrast, per-protocol (PP) analysis is defined as analysis of the subset of the ITT population who completed the study without any major protocol violations, i.e. the data are analysed according to what the participant actually had during the trial, rather than what they were supposed to have.
What is consort ?
CONSORT stands for Consolidated Standards of Reporting Trials. It is developed by the CONSORT Group to alleviate the problems arising from inadequate reporting of randomized controlled trials.
The main product of CONSORT is theCONSORT Statement, which is an evidence-based, minimum set of recommendations for reporting randomized trials. It offers a standard way for authors to prepare reports of trial findings, facilitating their complete and transparent reporting, and aiding their critical appraisal and interpretation.
The CONSORT Statement comprises a 25-itemchecklistand aflow diagram.
Every participant should be accounted for – all well reported trials should have a flow diagram that clearly outlines the flow of participants from eligibility, to randomisation, f/u and analysis.
There has been several official extensions of the CONSORT statement, including the ones for cluster trials, non-inferiority and equivalence trials, pragmatic trials, pilot and feasibility trials etc.
What is consort ?
CONSORT stands for Consolidated Standards of Reporting Trials. It is developed by the CONSORT Group to alleviate the problems arising from inadequate reporting of randomized controlled trials.
The main product of CONSORT is theCONSORT Statement, which is an evidence-based, minimum set of recommendations for reporting randomized trials. It offers a standard way for authors to prepare reports of trial findings, facilitating their complete and transparent reporting, and aiding their critical appraisal and interpretation.
The CONSORT Statement comprises a 25-itemchecklistand aflow diagram.
Every participant should be accounted for – all well reported trials should have a flow diagram that clearly outlines the flow of participants from eligibility, to randomisation, f/u and analysis.
There has been several official extensions of the CONSORT statement, including the ones for cluster trials, non-inferiority and equivalence trials, pragmatic trials, pilot and feasibility trials etc.
Informal care learning outcomes
Define ‘carer’ What are they ?
A carer is someone, who, without payment,
provides help and support to a partner,
child, relative, friend or neighbour, who
could not manage without their help. This
could be due to age, physical or mental
illness, addiction or disability.
How many carers are there ?
13.6 million carers
Gender inequality and caring ?
- more women are likely to be caregivers. 58% female caregivers compared to 42% of male caregivers.
- caring for someone can impact the carers physical and mental health
- caring for someone can impact their finance. Women caregivers are more likely to say they would worry about not coping financially compared to female caregivers.
56% women compared to 45% of men
Age inequality and caring ?
- 20 % of carers are between 18-24 years old
- 43% of carers are between 45-64 years old
- 22% are over 65 years old
- carers aged 65ys and older reported feeling more lonely.
Which area of the UK has the most caregivers ?
- South wales
- North East England
- North West of England
Describe what a caregiver does ?
Perform tasks of supportive character:
- wash patient
- clean patient
- toilet patient
- friendship/companionship to patient
- frequently involves co-residence. Often the carer will live with the patient.
What are teh effects of caring on the caregiver ?
How to the NHS support carers ?
What do caregivers givers say they need more support with ?
- more practical and emotional support
- training in caring activities (e.g. lifting)
- more respite care and short term breaks
What are the trends in the public policy of care ?
