Key Topic 2 – Subtopic 1: Published clinical trials and systematic reviews
These generally are preferred for substantiating claims, and have been subject to peer review, but studies still have important limitations. Here are some key points you need to consider when reviewing a claim:
- Do the study design, comparator, study population, and endpoints used support the claim being made?
- Do the statistical considerations support the claim, e.g. statistical power, was the primary endpoint met, were the analyses pre-defined, are the p values adjusted, has multiplicity been considered?
- Have the tools used in the study been validated?
Consider the following examples of claims and supporting clinical studies.
Example 1
Consider this webpage for the product RAPAFLO along with the approved US product information for RAPAFLO
Which of the following do you agree with?
- The main claim and imagery convey an effect on nocturia
- The clinical studies in the PI did not study nocturia specifically so cannot be used to substantiate this claim
- The clinical studies cited in the PI showed an effect on night time symptoms so the main claim can be substantiated
- A study would have to show an effect on work productivity to substantiate this claim
Ruling
This was the subject of an FDA warning letter. The FDA stated that the claim and imagery implied that RAPAFLO had been shown to improve sleep disturbance (quality of sleep) and work productivity. The clinical studies had evaluated a composite endpoint that included nocturia – but they did not measure impact on individual symptoms. Therefore the claims made could not be substantiated. The endpoints used in this study did not support the claim being made.
Note the FDA said: ‘Claims suggesting treatment benefits on nocturia, sleep disturbance and work productivity must be supported by substantial evidence as demonstrated by adequate, well controlled studies using well developed instruments that can validly and reliably measure these specific individual concepts.’
Example 2
In Australia AstraZeneca complained about promotional activities by MSD in relation to their product Vytorin (ezetimibe and simvastatin for hypercholesterolaemia). Two advertisements referred to the SHARP study which had been conducted in patients with chronic kidney disease. AstraZeneca argued that the claim “Now with patient outcomes data” constituted promotion of Vytorin for the reduction of cardiovascular events, which was not an approved indication for Vytorin.
The Committee considered that in the two Vytorin advertisements, the claim “Now with patient outcomes data” implied that the outcomes data from the SHARP Study were applicable to all patients who met the indications for Vytorin, which was not correct. The outcome data from the SHARP Study were only applicable to the study population - people with chronic kidney disease - and could not be generalised to all patients with hypercholesterolemia. Therefore the claim as it stood could not be substantiated. The study was in a patient population that did not match the claim being made.
MSD were fined $125,000 and had to issue a corrective letter to the journals where the advertisements were published.
