Blind Eye

John's post Overstepping Bounds describes pharmaceutical companies turning a blind eye to the provenance of clinical data.

Strange as it may seem (in trust terms at any rate if not in commercial terms) authorities in the west readily accept results of tests done in the third world when it comes to licencing drugs. So boundaries become meaningless when the mega rewards of getting a new drug accepted in the west are at stake.

In my SOAPbox blog, I have just commented about the security services approach to Information Sharing, (as described by MI5 chief Dame Manningham-Buller in the House of Lords on Thursday) which involves turning a blind eye to the provenance of intelligence data.

Foreign agencies don't tell us whether detainees have been tortured, and we are too polite to ask.

Manningham Buller argues that:

the desire for context will usually be subservient to the need to take action to establish the facts, in order to protect life

Scribe (of the recently renamed Into The Machine blog) discusses some of the political implications of this statement in a long and insightful post Rhetoric vs Debate: A Truly Public Strategy.

To uphold the image of saintliness, and to admit the realities only internally, behind the scenes, is even more damaging than acknowledging the state of global affairs as it really is.

In the pharmaceutical context, the regulators are faced with real ethical dilemmas - safety versus saving lives, the interests of the trial subjects against the interests of possible beneficiaries of a successful drug. We may observe various kinds of oscillation in regulatory behaviour. (See my previous posts on Drug Regulation and Trust Cycles).

Both in pharma and in security, there are strong indications of double standards here. Certainly not conducive to trust - but that's pretty obvious I guess. And it's not difficult to find hundreds more examples of double standards in public life. The question is a deeper one - how do we tackle double standards from a trust perspective?

Off-Label Trust

In a pharmaceutical context, Off-Label refers to uses of drugs that are not approved by the regulators and cannot therefore be printed on the product label or officially promoted by the drug company. More generally, it refers to any unauthorized or emergent use of a product or service. In this blog posting, I shall explore the implications of off-label for trust.

There is a regulatory process that is supposed to allow medical practitioners and their patients to trust pharmaceutical products. Under certain conditions, trust in the regulatory process (authority trust) generates trust in particular products (commodity trust). One of these conditions is strict adherence by all parties to the label.

• Users must confine themselves to using the product as specified on the label.
• Providers must confine themselves to promoting the product solely as specified on the label.
  

Whether the drug company salesforce is permitted to hint at off-label uses of a given product or not, this sets up a transference in which the nudge/wink (or enforced silence) of the salesman replaces the bureaucratic authority of the FDA.

Meanwhile, samizdat off-label information may circulate in the medical community, possibly based on direct/indirect trial/error experience by medical practitioners. This is a form of network trust.

Trust Cycle

Interesting press release from researchers at the University of California at San Diego.

Pharmacy dispensing volumes spike at the start of each month, because of the timing of government assistance payments . This leads to a spike in medication errors, resulting in a spike in mortality.

Thus trust goes in cycles. At some times of the month you get a rushed service, with little opportunity for personal (authentic) interaction. At other times, the pharmacist may be able to spend a little more time on each item, not just checking the technical correctness of the medication but also relating to the patient as a person.

There are three types of risk that may be affected by this cycle.

• Implementation risk - is this correctly dispensing what was prescribed?
• Composition risk - how does this medication interact with anything else the patient is doing/taking?
• Intention risk - is this the right prescription for this patient?

Trust is not reduced to a matter of technical competence, but embraces the human interaction (or lack of it) between the pharmacist and the patient.

original press release (January 5th, 2005)
relayed in ScienceDaily and in LeaderLog

POSIWID thinkers may note that the negative impact of this phenomenon falls disproportionately on those dependent on government assistance, thus effecting a kind of triage. God forbid there is any purpose in here.

Drug Regulation

Dr David Graham, described by the FT as a safety official, told US senators last week that the FDA system was broken because of a conflict of interest.

According to the Financial Times, the FDA once enjoyed a high reputation. Few consumers challenged its judgement. The FT writes: "Such trust is one reason why the US public has been more willing than Europeans to accept foodstuffs containing genetically modified organisms."

So what has eroded this authority trust? The FT identifies two factors that may be relevant.

1. One can detect a regulatory cycle in drug approval. Testing standards became tougher after Thalidomide, were relaxed when AIDS stimulated demand for new and experimental drugs, and so on.
2. Division of responsibility and inconsistent handling of drugs at different stages of the innovation lifecycle. Approval follows one process; monitoring of approved drugs is done by a different department and follows a different process.
   

Oscillation and internal contradiction are both natural phenomena of complex systems, and tend to have a destabilizing effect on trust. One obvious response to this is to distrust complexity. But denial of complexity may merely create a false illusion of trust. Authentic trust may just have to accept oscillation and contradiction.

So whither the FDA - towards a restoration of authority, or towards an engagement with authenticity (if we can believe that)? Either way, a more intelligent and honest attitude to risk (as recommended by the FT) will be useful.

Source: FT Editorial No Pain-Free Option (November 20, 2004)

Clinical Validation

Hypotheses are checked not against impersonal trials of their adequacy but against testimonials, case studies and assessments of success made by parties with a stake in their outcome.

Frederick C. Crews, Out, Damned Blot! New York Review July 15 2004

Drug companies only publish the results of favourable trials. Some people argue they should be forced to publish all results, whether favourable or otherwise. However, this could simply cause the drug companies to engineer the trials more carefully in advance, to reduce the risk that the trials might reveal anything inconvenient to their commercial agenda.

Marcia Angell, The Truth About the Drug Companies, New York Review July 15 2004