Clinical Trials, Placebo Effects, Complementary Medicine Flashcards
The placebo effect is particularly profound in clinical trials of which type of drug?
Anti-depressants
What were the conclusions of the House of Commons Science and Technology Committee report on homeopathy in 2010?
That it is ‘scientifically implausible’
What were the advantages in the randomised controlled trial with acupuncture vs. Usual care in treatment for chronic headaches?
In those who had received acupuncture:
- there was greater reduction in headache severity at 12 months
- fewer headache days per year
- improved quality of life
- less medication, fewer GP visits, fewer days off
- cost effective; less expensive than Sumatriptan
What needs to be clearly defined in a clinical trial?
The objective needs to be clearly defined
Questions can be prioritised into primary & secondary objectives
What is the possible issue with complementary / alternative medicine?
Much of it is not evidence-based and doesn’t stand up to scrutiny
What is the placebo effect
Effect of a treatment arising from a patient’s expectations and response to the treatments, excluding the actual action of the treatment
*in medicine - the response observed after inert / inactive treatments
What is the nocebo effect?
People reporting adverse side effects after taking a placebo
What is the difference between ‘Superiority’ and ‘Non-inferiority’ in clinical trials?
Superiority - designed to show that one treatment is better than the other
Non-inferiority - designed to show that a new treatment is ‘not unacceptably worse’ than the current standard treatment
What is the % of complementary medicine that is provided privately?
90%
What is ‘Superiority’ in treatment comparison?
Used to demonstrate that one treatment is better than another
(Needed in placebo trials)
What is ‘Non-inferiority’ (in treatment comparison)?
The non-inferior margin is the pre-determined margin of difference between new and standard treatments.
It represents how much worse the new treatment can be compared with standard treatment, and yet still be considered ‘similar’ or ‘not worse’ than standard treatment.
Used to evaluate other factors (i.e. cost / side effects)
What is homeopathy?
Applied the principle of ‘like cures like’
‘a form of complementary medicine in which ailments are treated by minute doses of natural substances that in larger amounts would produce symptoms of the ailment’
So a substance is highly diluted, effectively a sort of placebo
What is ‘Equivalence’ (in treatment comparison) ?
Used to demonstrate that a treatment is the same - no better or worse, than an existing treatment
Also used to evaluate other factors (i.e. is it better in terms of side effects / cost?)
What is considered the ‘gold standard’ for clinical trials?
Randomised clinical trials
I.e. randomly allocating treatment to different people / randomly allocating people to different treatment
What is an open label clinical trial?
Both the clinical / patient know which arm / intervention they are receiving
What is a single blind clinical trial?
Patient is unaware of their treatment assignment
What is a randomised clinical trial?
Patients are randomly allocated to different arms / treatments in the trial
What is a placebo controlled clinical trial?
Some patients get the ‘active’ therapy and some get a placebo
This has to be at least single-blinded as the patient cannot know whether they are receiving the active or placebo treatment
What is a parallel arm clinical trial?
Standard A vs. B
People are randomised
Comparison of 2 interventions / treatments
What is a multi-arm, multi-stage clinical trial?
Enables an undergoing trial to stop or add arms as it continues recruitment, and to evaluate the efficacy of certain arms of the trial
(An arm of a clinical trial is a group of patients receiving a specific treatment, or no treatment)
What is a factorial clinical trial?
Tests all combinations of 2 or more treatment regimens
E.g.
Testing A vs. B
then A with placebo / B with placebo
This can be done with fewer people
What is a double blind clinical trial?
Neither the clinician / patient know whether they are receiving the active / placebo treatment
What is a cross-over clinical trial?
Every patient has both treatments (i.e. A then B or B then A)
What is a cluster randomised clinical trial?
Participants are randomised by unit (e.g. GP surgery, family, community)
What is a clinical trial
Scientific investigation that examines and evaluates the SAFETY & EFFICACY of different therapies in HUMAN subject
What 5 factors contribute to patients’ response to treatment?
Type of procedure
(E.g. it is perceived that surgery > injection > pill)
Previous experiences
Medicines
(E.g. perception that big-branded pills in high quantity > smaller pills in low quantity, colour of pills)
Presentation - by the doctor / advertisements etc.
Individual belief about the treatment
What factors can help predict placebo responses?
Brain connectivity & structure
Psychological factors
E.g. emotional awareness, capabilities in describing inner experiences, greater openness to experience
What example shows how evidence can change between clinical trials?
The use of Echinacea for the common cold
What does PICO stand for in clinical trials?
P - population (patients)
I - intervention
C - comparison (control) group
O - outcome
(T - time)
In [population], what is the effect of [intervention] on [outcome] compared with [comparison group]?
What causes the placebo response?
The psychological / emotional meaning that defines the response, which can also result in physiological changes
*Not the placebo itself as they are (generally) inert
What are the 5 different types of clinical trials?
- Open label
- Placebo controlled
- Single blind
- Double blind
- Randomised
What are the 5 different designs of clinical trials?
- Parallel arm
- Cluster randomised
- Cross-over
- Factorial
- Multi-arm, multi-stage
What are the (stereotypical) profiles of those who use complementary / alternative medicines?
Those with anxiety, depression, long-standing illnesses
Those with poorer mental health and lower levels of perceived social support
More women than men
University educated / in active employment (possibly because it costs money)
Those who appear to pursue healthy lifestyles
What are some of the reasons that people choose complementary / alternative medicine ?
To cure disease / treat symptoms if standard treatments aren’t working
Side effects of orthodox treatment
‘Holistic approach’
Feeling listened to - given more time & attention (linked to placebo effect)
Feel more in control
What are examples of social factors related to Covid that may have influence the placebo effect in clinical trials?
High profile in the media
Urgency & societal need
—> could have made people more keen to participate / more worried about adverse effects
What are examples of placebo interventions?
Inert pills, drugs, injections
Sham surgeries
Inactive medical devices
Non-effective / sham acupuncture
What are complementary & alternative medicines?
Therapies not taught at medical school or practised within established institutions
What % of GP practices offer complementary / alternative medicines?
50%
Name 5 different types of medical intervention that require trialing
- Conventional medicine
- Complementary medicine
- Medical devices
- Surgery procedure
- Physiotherapy
How many phases of clinical trials are there?
4
How many (%) UK citizens use complementary medicine per year?
15-20%
How many (%) UK citizens use complementary medicine in their lifetime?
50%
Give 8 examples of complementary / alternative therapy
- Massage therapy
- Aromatherapy
- Acupuncture
- Osteopathy
- Herbal medicine
- Hypnotherapy
- Traditional Chinese medicine
- Nutritional therapy
Describe phase 4 of clinical trials
Tends to be after a regulatory authority has approved the drug / treatment
Large-scale = 10,000s of individuals
Adverse event monitoring
Describe phase 3 of clinical trials
Assesses the risks / benefits of the intervention
Compares the treatment with the current standard (i.e. whether it works / cost effectiveness)
Done in a larger sample of people - 100s-1000s
Describe phase 2 of clinical trials
Investigates the activity, safety & tolerability of the drug
Carried out in people with the disease
Test group of ~ 80-100 individuals
Describe phase 1 of clinical trials
Investigates pharmacology & drug safety
Usually done in healthy human volunteers (but sometimes in those with the disease)
Very small group (e.g. 10-20 people)
Very closely monitored
Clinical trials need to be properly… (4)
- Designed
- Performed
- Analysed
- Interpreted
Can the placebo effect significantly impact the outcome of clinical studies?
Yes
