Oseltamivir: the real world data
BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g2371 (Published 09 April 2014) Cite this as: BMJ 2014;348:g2371
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It is understandable that the company-sponsored trials of oseltamivir focused on ambulatory patients with influenza. That is where the big sales are, and profits come from selling large amounts to many such people. From the health care system view, the greatest concern is about the seriously ill who are admitted to hospital and intensive care, and elderly in nursing homes. These are at high risk of death, and their care costs huge effort and funds. But the sales of oseltamivir for these purposes would be relatively trivial, so drug companies would see little return on investment in difficult trials on such patients.
Therefore in our current "private enterprise" drug sales system, it is entirely reasonable that health care systems should fund the trials that would demonstrate whether this drug makes a difference. They are also more likely to ensure that the trials are done properly, without built in bias, and reported fully and fairly, so we can make better decisions than if we rely on the company trials. As Dr. Krumholz points out, there are large stockpiles: since these are already available, at least part of the costs of such trials has already been incurred.
Competing interests: No competing interests
Re: Oseltamivir: the real world data
The list of pros and cons concerning non-interventional (=observational) studies vs. controlled clinical trials misses one important point.
At least since the mid-1990s all pharma-sponsored interventional trials must have been conducted adhering to ICH E6 (also called the GCP guidelines). These regulatory guidelines require, among other things, monitoring, source data verification, and drug accounting. All these measures are to verify to the extent possible that the data are based on true facts, i.e. the patients existed, had the indication in question, and were actually treated with study medication and assessed and reported according to the protocol. In the USA for a long time, and in Europe at least since about 2004, sponsors have had to envisage regulatory inspections verifying that the study has been conducted in this way.
None of these rules are compulsory for NIS. These studies are explicitly excluded from any GCP regulation, although some sponsors sometimes might deliberately announce or even implement some of the GCP rules. Nevertheless, NIS have hardly ever been inspected by authorities in the past. So: Little to no control, no risk of inspection.
Then readers should understand how physicians (I hesitate writing investigators in case of NIS) normally get paid for participating in NIS: by completed CRF. Nothing else.
The consequence of all these aspects is that there is the risk that some data from NIS might have been completely invented. You may speculate that this rate would be as low as 1%, but can anybody really exclude a rate of 50% for every trial? And could 1% from the set of important data not also be relevant?
So, beside the design, there is one other important aspect why NIS should usually be considered as hypothesis-generating (at best), and people should be very careful with writing “prove” when relying on NIS.
Competing interests: No competing interests