Induction of Opioid-Dependent Individuals Onto Buprenorphine and Buprenorphine/Naloxone Soluble-Films. Strain EC, Harrison JA, Bigelow GE. Clinical Pharmacology and Therapeutics 2011 89: 443-449
Dear Colleagues,
I was intrigued when searching for research on the mooted new ‘wafer-film’ form of buprenorphine to find that Dr Strain and his experienced research colleagues have performed a detailed and thorough drug induction trial which nevertheless seems to be of little or no utility to the clinical field. The appropriate test for any new medication is a randomised, blinded comparison with an established intervention using standard outcome measures. In the field of dependency these include retention, drug use parameters, side effects, sero-conversions, mortality, etc.
In this study the authors compare a newly introduced formulation of an old drug (buprenorphine/naloxone ‘film’) with a non-approved and possibly non-validated medication (buprenorphine film). By going to complex lengths to document withdrawal differences (see multifarious bewildering graphs), the authors appear to believe it is important to determine if there is any such difference, despite neither being a known ‘quantity’ to start with.
It is a false premise that finding no difference between two treatments proves their equivalence. Such a conclusion may be a statistical ruse rather than a rubric, as pointed out by Walter Ling many years ago. Strain and colleagues do not make such a claim, yet it is possible that others may misinterpret the work in this way, just as has happened with Suboxone (combination with naloxone) and Subutex (pure) which remarkably have still yet to be subjected to even simple equivalence testing. The reader is still left with the question of what exactly Strain and colleagues were trying to demonstrate in this paper.
[This question was answered in a recent lecture by Dr Strain at a function organised by the manufacturer in Sydney, Australia: see my summary on the subject in which it is state that the manufacturer was fighting to have the FDA recommendation to do inductions only with pure buprenorphine, now a cheap generic drug in some countries.]
While it would be beneficial to avoid or minimise withdrawal symptoms during induction, it is not clear whether this is linked to retention rates. In our experience some of the most successful buprenorphine and methadone recipients had unpleasant periods of withdrawal during the induction period.
Another weakness of their study is that their treatment induction bears little resemblance to normal clinical practice, further limiting relevance to the real world. They gave multiple doses of buprenorphine over many hours, something which is not used routinely either in clinics or community practice to my best knowledge. Furthermore, it would probably be costly and difficult to implement in the field.
It is not at all clear why these authors include the issue of drug packaging. In the abstract and twice again in the text the reader is informed about new individual packaging which is alleged to be safer than the existing product. Yet both are marketed by the same company which also supported this research. Rather than blister packs which are used in most of the world, in America buprenorphine is apparently dispensed as loose tablets (and now wafers). The new wafer formulation reportedly comes as individual unit-dose format with child resistant packaging. This aspect was not tested in any way in the paper and it would appear that the researchers are taking liberties by introducing this matter into a paper which ostensibly examines the physiological effects of introducing two buprenorphine products to dependent patients and in which most medication was given under supervision such that the packaging format was irrelevant to the outcomes. This is quite unlike the manner in which buprenorphine is commonly used in America and France … but not in most other countries which use supervision (evidence based) treatments. The irony is that most of the evidence was from studies performed in the United States where it was apparently overlooked in the Act of Congress which gave a waiver allowing doctors to prescribe it from their offices as a drug to be dispensed like any other drug from the pharmacy.
It is further claimed that serial numbers will allow tracking for buprenorphine films which may be diverted onto the black market. This would depend on chain-of-custody supply as well a new layer of detailed record keeping the cost of which is unknown, nor is it known if this type of measure can be effective. In short, this is a peccadillo and should be tested properly rather than being speculated upon here.
The first lines of the abstract read more like an advertisement than a serious scientific study: “[buprenorphine film product] provides unit-dose, child-resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets.” Note that inventive drug users have already found ways of exploiting the increased solubility of buprenorphine wafers as described in a front page New York Times article entitled “When Children’s Scribbles Hide a Prison Drug”
