OK, let's break down these terms: * multicenter: the study was conducted studying animals at multiple clinics/locations * prospective: study subjects are enrolled and followed BEFORE the disease or the outcome is observed (in this case the painful procedure/analgesic response. Prospective studies tend to be less prone to bias, compared to retrospective studies (like evaluating historical patient records of prior disase/treatment/outcome). * randomized: enrolled subjects are assigned to treatment or control groups randomly. Randomization can be an effective way to minimize intentional or unintentional bias in a study. For example, in a non-randomized study an investigator might (intentionally or unintentionally) place all of the younger subjects in the control group and the older subjects in the treatment group. Now you have two things that could contribute to a difference between controls and treatments, the actual treatment AND AGE. So if there was an improvement in the treatment group, which thing did it, treatment or age? Randomization reduces the occurrence of biases like that. * masked : this is also called blinded. In masking, one or more categories of study workers are blinded as to whether subjects are in the treatment group or the control group. I'd have to look at the full experimental write-up to know exactly who was blinded, but at a minimum the study workers assessing the analgesia should be blinded as to whether they are observing a treatment, or a control animal. This can be complicated! A vehicle control cat is unlikely to be dysphoric/euphoric, so if I am a study worker and I see a dysphoric cat, I will likely be biased to assume that it has been treated with drug, and that could in turn bias my assessment of its pain. * vehicle control : this is a form of placebo control. the treatment group gets vehicle+drug, the control group gets only vehicle. You will also read about "active control". In this case it is an intramuscular injection of bupe. This allows a comparison between all the things that can interfere with transdermal absorption, and an administration of bupe that bypasses the vagaries of transdermal absorption and lets the investigators know what a more reliably absorbed, roughly equivalent dose, is capable of. Placebo controls and vehicle controls are also related to masking/blinding. In the ideal world, almost no one should know whether a patient got the control treatment or the test treatment, until the study is completed and the data analyzed. This reduces bias in assessing the effect of the treatment. * pilot : a pilot study is an early study, often used to explore dose, timing, effectiveness in a smaller number of animals to aid in designing a larger subsequent study.

Remember, the two basic things that FDA requires for approval are 1) actual evidence that establishes the drug is an effective treatment for the specific indications in the application (in this case post operative analgesia in cats) and 2) typical use of the drug is unlikely to cause injury that is disproportionate to the risk that the disease presents. For example, most anticancer drugs may cause injury, but the diseases that they treat have a much greater risk of injury if left untreated. But there would be a much higher expectation of safety in a drug to treat kennel cough, a disease which is rarely fatal and often self-limiting. So here, in this data we'll see studies designed to provide evidence of effectiveness, and studies designed to provide evidence of safety.

This drug is not exactly an earth-shaking discovery. "BuTrans", from the notorious Purdue Pharma (in a legal settlement, Purdue Pharma agreed to disband as a business) was FDA approved for humans in 1981, is a transdermal buprenorphine patch.

Beyond our scope, don't worry about this.

Inclusion and Exclusion criteria are important! Remember, you are trying to keep the treatment group and control group as similar to each other as possible.

To me, the executive summary (not sure why they call it that!) seems to be pretty dialed-down for a non technical audience. This is a great skill to get better at, although at points the basic language can get a bit confusing

This concept is called dose proportionality, and it is a really handy thing to know. What they are saying here is that beyond a dose of 30mg/cat you lose dose proportionality. This implies that below that dose, if you double the dose you should see approximately a doubling of plasma concentration--That's dose proportionality!

This is a nice & clear explanation of "flip-flop kinetics"! Far more common is the situation in which absorption is fast, compared to the slower elimination. In that far more common scenario, half-life (aka terminal half-life) is driven by clearance. Here, the rate of absorption is so slow that whatever drug is absorbed is quickly distributed and cleared (but of course during that process some drug gets to its CNS targets and binds (tightly!) to them.

Not surprising since bupe is really, really lipophilic.

this is an example where oversimplification distorts the facts. "bind as strongly" is not accurate, and it disagrees with "high binding affinity" in the previous paragraph. Bupe does bind with very high affinity to the mu opioid receptor. It is a partial agonist because that tight binding is not capable of causing the conformational change in the receptor that is necessary to produce a maximal receptor response. The ability to fully activate a receptor is not a function of the tightness of binding (if that was the case naloxone, which also binds tightly, would be a full agonist). It is a function of whether the binding induces the 3-d changes in the receptor that cause it to signal its activation to the interior of the cell.