Focussing on secondary endpoints has already been covered, but what do trial investigators do if both the primary and secondary endpoints are unconvincing?
Data dredging may produce a statistically more convincing result. Data dredging is the process of analysing all the trial data looking for outcomes that are statistically significant; it produces post-hoc or tertiary endpoints.
These post-hoc endpoints must be treated with caution as the study was not set up to directly collect, examine and answer any questions relating to this composite data group. The statistically acceptable level for a result occurring by chance is 1 in 20. This means that if we conduct 20 post-hoc analyses one may have been statistically significant purely by chance.
For example, a post-hoc analysis of the ISIS-2 study1 found that aspirin therapy was associated with increased harms in patients born to Gemini or Libra star signs. Clearly this is nonsense and confounds our conclusions.
A more recent study that made use of post-hoc analysis was ASCOT-BPLA2. As already discussed the conclusions reached in this trial should be treated with caution.
- ISIS-2 Collaborative Group Randomized trial of IV streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction. Lancet 1988;2:349-360.
- Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a mulitcentre randomised controlled study. ASCOT Investigators Lancet 2005;366:895-906.
The Summary of Product Characteristics for Paroxetine (Seroxat) has been updated to include an additional warning against using this drug in the first trimester of pregnancy.
This new information has been reported to clinicians in a letter from the manufacturers and is also the subject of a Medicines and Healthcare products Regulatory Agency (MHRA) Safety Warning.
This new information has come to light following a retrospective epidemiological study of birth defects in infants born to mothers who took antidepressants during the first trimester of pregnancy. The results of the study are available online in the GSK Clinical Trial Register.
The MHRA advise clinicians that:
- paroxetine should only be used in pregnancy where strictly indicated and where the benefits outweigh the risks
- until further investigations are conducted, paroxetine may not be the most suitable selective serotonin reuptake inhibitor (SSRI) in women who are or plan on becoming pregnant
- if the decision is made to stop paroxetine, this should be done gradually over a period of several weeks
The MHRA also have the following advice for patients:
- women taking paroxetine who are planning a pregnancy should consult their doctor to discuss treatment options
- pregnant women currently taking paroxetine should not stop treatment abruptly but should discuss their treatment at their next routine appointment with their doctor or midwife
Action: Clinicians will need to be aware of this latest advice. It may also be beneficial to ensure that midwives working with your surgery are aware of this advice and the implications.
The patent on Lansoprazole (Zoton) has expired and generic versions are now available for several generic manufacturers. The price of these new versions is expected to fall over time.
The patent expiry will not affect the FastTabs because an additional patent on the formulation protects this product. Only generic prescriptions for capsules will be affected.
As recommended in the formulary, omeprazole remains the first line choice and lansoprazole makes a good second choice based on clinician experience and the new availability of a generic to drive the cost down.
Action: Clinicians should still use omeprazole as first line with lansoprazole capsules as second choice.
The software used to make this site possible has been updated (on Boxing day no less!) and the changes mean some improvements have been made to how subscriptions are managed.
Users who are currently subscribed will continue to get email updates but this will continue to be a summary of the post on the site.
By registering for the new system you to customize how you get your email. Registered users can:
- subscribe to individual categories
- select plaintext or html email format
- select summary or full email content
Once you register you can log on to the site and manage your preferences for how you receive your free update notifications.
Action: We urge all current subscribers to make use of this new feature because future improvements will focus on the new system of subscription management.
Two further changes have been announced that will affect the availability of some inhaler devices used in the treatment of asthma.
Firstly, Nedocromil (Tilade) inhalers are being replaced with a CFC-Free version with immediate effect. Patients should be advised to clean this new device as per the patient information leaflet to avoid blockages.
Secondly, the CFC containing inhaler, Sodium Cromoglicate (Intal) will be discontinued. This appears to only affect the Intal brand with no indication if the other Sodium Cromoglicate containing products (e.g. Cromogen) will also be affected.
Changes in propellant are likely to affect the sound and taste experienced by the patient. Patients should be warned to expect these changes so their confidence in the treatment is not affected.
Action: Clinicians who treat respiratory disease should be aware of the on going changes in asthma devices. Information about the changes in inhalers should be provided at the point of prescribing and dispensing.