1 Boring Old Man

The Latin phrase deus ex machina [from deus, meaning "a god", ex, meaning "from", and machina, meaning "a device, a scaffolding, an artifice"] was referred to by Horace in his Ars Poetica, where he instructs poets that they should never resort to a "god from the machine" to resolve their plots "unless a difficulty worthy a god’s unraveling should happen"… Aristotle criticized the device in his Poetics, where he argued that the resolution of a plot must arise internally, following from previous action of the play.

The ancient advice to poets to make the resolution of their tales follow from the plot as presented to the audience remains a critical principle in literature. We want Poirot to find the murderer[s] among passenger[s] on the Orient Express, not some new outside character. We don’t like our stories ended with divine intervention or the unexpected landing of aliens. If our settlers are saved by the arrival of the cavalry, we at least want to have known they were on the way. And, by the way, that’s our beef with Clinical Trials of medications. We’d like for the reports on their efficacy and side effects to flow logically from the results of the trial itself. And that hasn’t been the case in many of the Clinical Trial reports in recent years.

History: But we didn’t know it, at least I didn’t. The Clinical Trials in question weren’t complete lies. They were subtly manipulated by the initial design, by the choice of analytic methods, by omission of data, by non-publication of negative results – a compendium of techniques that mirrored Johnny Mercer’s old lyrics:

You’ve got to accentuate the positive
Eliminate the negative
And latch on to the affirmative
Don’t mess with Mister In-Between

Flash forward: As the corruption of the Clinical Trial literature became more widely known, opposition arose from a variety of foci. The Clinical Trials themselves weren’t the central Achilles heel in the system, it was in the handling of the raw data – the space between unblinding the study and the publication [or burying] of the results. That was the vulnerable spot, because the pharmaceutical companies had control of access to the raw data as intellectual property [the why of that and how it came to be is beyond me]. So the consensus was that the solution to the problem was to insist that the raw data from all Clinical Trials be made available for independent analysis. Thus began the many campaigns…

An Aside: As the corruption in Clinical Trials became more widely known, the pharmaceutical companies began to take a small beating in the courts, settling more and more suits, civil [blue] and criminal [red]. But the charges were things like false advertising or off-label promotion rather than directly for deceitful data analysis. And they went out of their way to avoid retracting the targeted articles or admitting their data manipulations. They went to extremes to deny such wrong-doings, in one case even when they had essentially admitted to it in a $3 B settlement agreement [the only enduring contract…].

Until Last Week: As the various campaigns for Data Transparency and grown, the call has reached into governments and regulatory agencies. The pharmaceutical industry has had to make concessions, fighting the whole time to maintain their hold on the ownership of Clinical Trial raw data. They’ve argued that the reasons are patient confidentiality, protecting trade secrets, spawning innovation, and they speak as if this is some kind of fundamental right – a copyright or a property. A major breakthrough came when the European Medicines Agency [equivalent to our FDA] announced that they were going to begin releasing the Clinical Trial data once a drug was approved, and actually began doing it. It was slowed down by the suits from AbbVie and Intermune, but they were overturned and withdrawn. The European Parliment supported Clinical Trial registration in April and things were again on track for the EMA transparency initiative to move forward.

Now: Then last week, the EMA released an altogether different and very restrictive policy claiming it was little changed [to be continued…]. But that’s simply not true. It was radically changed [the U-Turn…, the end game…, a decision to reconsider…, a crushing setback…]. Did the EMA make this compromise with AbbVie to get their suit dropped? Does it have something to do with AllTrials sidling up to GSK? Did PHARMA threaten the EMA with more suits? Was this in the cards all along? Conspiracy theories abound. None of us know the answers to any of those questions. But independent analysis of Clinical Trial data sure got a lot harder in this last week – perhaps too hard. But this time, we know some things for certain. The Deus Ex Machina in this story is the pharmaceutical industry. They’re going to fight to the finish to protect their right to distort the results of Clinical Trials. And however the U Turn went down, they did it behind closed doors. It’s being presented so far by the EMA as a fait accompli, and it may well be – something of an 11th hour coup.

There’s something terribly wrong with this story. There’s a large cadre of people – doctors, scientists, healthcare advocates, and patients who are only united by an outrage at the disreputable behavior of the pharmaceutical industry in regularly distorting the scientific information from the Clinical Trials of their drugs. We want to see the raw results and are willing to put in the time – mostly unfunded – to check their analyses for accuracy. Their misbehavior has been blatant enough and damaging enough to require that kind of vigilance. And yet the European Medicines Agency is rolling out a program that makes doing that extremely difficult, has caveats that allow these companies ways to continue to hide and distort data, and have a listing of potential penalties we might endure and oaths we have to swear that are sure to discourage any but the most hearty.