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Wednesday, December 22, 2021

Big Pharma Talks ...


 (*Edited - content added regarding "The placebo effect," considering the possibility of subscription-style contracts)


So this is the busiest time of the year, at work, these last few weeks of the year, as it is for pharma, trying to tie up loose ends before new products launch -  so I'm just taking a momentary break from a particularly long job to give a general comment.

I've mentioned what I do before, which is transcribe interviews for an independent marketing company for payers, regional, national, and international -   and KOL clinicians, or key-opinion leaders, experts in a particular field or disease state, both physicians and pharmacists, both academic and private practice - and PBMs, or pharmacy benefit managers, who handle large-scale pharmacy plans for insurance companies.


Typically, these are held separately - one interview is with a payer alone, a separate one with a KOL, etc.

Every now and then, they hold the interviews with both a payer and a clinician together at the same time.

Just a general comment - why don't they do these more often? LOL.


They always go very well, nobody fights, they always really listen to each other to try to understand where the other side is coming from, and they're enlightening for both parties as to what the other side of the healthcare system is going through and has to deal with, as well as enlightening to the interviewer, and me. 

(I know, who cares if I gain insight, I'm a nobody just transcribing these, but still, point being, we all gain more insight into how these things actually work).

And both the payer and the KOLs always say afterwards, "Wow, I learned so much from this - I had no idea this was going on, on your side."

Right?


IDK, maybe they're too expensive to do -  or they have a hard time  scheduling them both at the same time, coordinating schedules?


If the reason is expense, pfft, Big Pharma -  you know you have enough money to do it, in your R&D budget (which you're going to bake into the  high WAC price anyway) - so why not spend a buck for prevention now, rather than lose thousands to millions later, because you thought insurance companies were at your mercy and would have to pay for your drug, and you  thought physicians would pressure them to cover it - but you learned pretty quickly with Aduhelm, that wasn't always the case, now, didn't you? ;)

If you do these pre-launch and at-launch interviews, you're going to know beforehand exactly how payers and clinicians view your drug, or at least a ballpark idea, including even their reaction to test prices. 


So ... can we infer from the fact that the only time they seem to do these types of interviews is when a breakthrough treatment is expected to obtain FDA approval (or recently approved) -  and that they don't do these types of interviews ordinarily, because pharma already know that most of their new drugs coming to market are not breakthrough treatments, do not offer significant incremental benefit, and are simply "me-toos" - but still want to charge a premium price for them anyway or-? ;)


Because the fact is, most physicians have no idea what something costs, unless the patient comes back and tells them they can't afford the copay or coinsurance - and they really don't want to be influenced by cost to the insurance company, because they want to pick the best drug for the patient regardless. 

They may have a rough idea of whether something is expensive or not, but they'd honestly rather not know, because their main goal is choosing the best and most effective drug, with the least side effects, to treat the patient.

At most, they then check to see whether or not their insurance covers it, but they don't usually know the actual price, and they definitely don't know what the patient's copay/coinsurance is unless the patient  calls/comes back and tells them. 

I understand why they don't want to know the price, so as to not let it interfere with best drug choice - and yet in this day and age, perhaps they really should?


Now - insurance companies know very well what things cost, and they're the ones making sure that the efficacy and side-effect profiles make the drug worth the price.

And they're getting very frustrated with the amount of "me-too" medications that come in, with similar efficacy and safety -  making their trials versus placebo instead of direct competitors -  and yet still trying to find reasons why they deserve a premium price to their direct competitors anyway lol.

Speaking of "versus placebo" trials, they're also getting very frustrated with drug trials still going up against placebo, or non-comparable drugs, instead of direct competitors, if they already exist in the class.  


Now, going up against placebo makes sense, when there's no other comparable drug, the new drug will be a first-in-class drug - i.e., new vaccines or new mechanisms of action - because there is nothing else to compare it to.

It also makes sense if the "placebo" is actually the current standard of care - like when the first monoclonal antibody drug came out for rheumatoid arthritis and psoriasis, it went up against steroids  as the placebo -  but still a different mechanism of action than the new drug.


But it does NOT make sense if there are comparable others already  existing on the market, in the same class.

(To be fair, sometimes the trials begin before any competitors come out, too - but they usually know what's in the pipeline coming already).


However, by and large, there already are direct competitors on the market, they just choose something that's not really a competitor to make themselves look better. 


HOWEVER - "The placebo effect" is real.

In fact, in every single trial that's done, there is always a placebo effect - meaning at least a small proportion of people taking the placebo improve - and not just subjective reports from patients - their objective lab markers actually improve. 

By the same token, there can also be negative side effects reported with placebo, too - headaches, GI upset, dizziness, fatigue.

In fact, every single new drug in a "versus placebo" clinical trial is actually competing with placebo effect rather the actual placebo medication itself.


Why is there always a placebo effect?

There are (at least) 3 possible causes theorized, which depend on how much placebo improvement was reported - how many patients showed improvement or worsening on placebo: 


1)  If the placebo effect is large -  and the placebo is actually either the current standard of care (different mechanism of action than the new drug, but still contains active ingredients) or older treatment, rather than a true placebo (no active ingredients)  - it could signal that the standard of care or older agent acting as placebo is more effective than previously believed, or on the negative side, has a worse safety profile if the placebo appeared to cause more side effects.

In that case, it becomes a matter of how much better the new drug is than the current standard of care acting as placebo.

 

2)  If the placebo effect is large - but the placebo is a true placebo (meaning no active ingredients) -  this indicates that something was wrong with the study -  either in the study design itself or in its implementation.

If a study design flaw, it's usually the patient population chosen for the trial - i.e., the study size was too small, they were already on prior or concurrent medication, or they weren't screened for genetic contributors or other comorbid conditions, which would of course affect the study's outcome. 

It could also signal that the "controlled" study wasn't very controlled -  parameters were not adhered to, and therefore flawed.

 

3) If the placebo effect is small, and a true placebo was used -  meaning no active ingredients, just saline injection or water or sugar pill - the improvement is likely psychosomatic, psychological - people believe they're possibly taking something that's going to make them better, and so some of them actually do (but not all). 

 

HOWEVER,  there is always a placebo effect in these trials - if large, it's a study problem;  if small, it's normal - likely psychosomatic rather than the first two reasons. 

Never underestimate the power of the mind over the body;)


Thus, a new drug is considered effective if there is a statistical clinical significance of improvement VS. the actual placebo effect rather than versus the actual placebo medication - and sometimes, the FDA will pass the drug even if the delta between improvement on placebo and the new drug isn't very significant.



Regardless, point being, at present, the FDA incredibly still allows approval based on new drug VS. placebo trials, even if the drug only did slightly better than placebo, even if the placebo effect was large, and despite there being a direct competitor on the market when the trial began -  for what reason I don't know.

In fact, having transcribed these interviews for international government payers, as far as I'm aware, we are the only first-world government in the world that still does so -  at least to the degree that we do.


Our FDA also allows for short trial times, such as 12 weeks, whereas other governments do not, requiring typically 24 to 26 weeks/about 6 months - BUT - if the FDA approves a drug, other governments will evaluate it at least, and most pharma companies also do an ongoing open-label extension study and publish those after launch.




Regardless, nowadays, the entrance of many new brands and generics don't lower the price anymore, as a market system is supposed to.

That is because of varying contracts, where brands are now offering steeper rebates than the generics can offer to the PBMs and insurance companies (and especially the PBMs insurance companies contract with), which can actually make the branded drug cost less than a generic, in the end, usually accomplished by engaging in a "portfolio" contract containing all of the company's products .


(Meaning the contract terms are that you buy not only that drug, but a certain manufacturer's "portfolio" of products, particularly at a certain volume, and you get either steep discounts or substantial rebates back on not only that drug, but on all the other drugs by that company).


As we all know, rebates are the problem, but nobody has any idea of how to fix this system, without government price regulation on pharmaceuticals, which of course nobody in America wants - Trumpers especially would lose their freakin' minds lol.


I personally think a "Netflix" style subscription system might work, a pay-as-you-go system, rather than upfront full purchase - meaning if a drug is found effective and worth its value, then the insurance company keeps paying for the subscription - if not, they simply "cancel their subscription."

This is similar to a value-based contract, but with one crucial difference - you can cancel your subscription for any reason you like -  no proof needed to cancel, no arguments with the manufacturer over markers for efficacy.

You like it, you continue paying for it; you don't like it for whatever reason, you cancel - simple. 


And in fact, these days, it's not so much the rebates going directly to the insurance companies that are the problem, because they've become much more transparent about where their rebate dollars are going - usually to lower your premiums.

These days, it's more likely the PBM that the insurance company has partnered with to manage the pharmacy benefits and negotiate the contracts with pharma for them, who offer no transparency at all about where their rebate dollars are going - which is why certain states have enacted mandates on them, or at least requesting more transparency from PBMs on where these rebate dollars actually go.


This is because nowadays, it's not so most the commercial insurance companies that are getting the big rebates anymore, it's their PBMs they're contracting with.

They get the biggest chunk of rebates first, because they are the ones actually negotiating the contracts directly with manufacturers - and they're not very transparent about where these rebate dollars are going.

Thus, the health insurance plan that uses them gets whatever rebate money is left, after the PBMs take the lion's share, with which they to try to reduce your monthly premiums  (which unlike PBMs, they have become at least somewhat more transparent about) - and then whatever measly amount is left goes towards a patient's copay/coinsurance.


Though there are patient-assistance programs for patients offered by pharma, you're not eligible for them if you're on Medicare, for some unknown reason - despite the Medicare population needing them most - which is why some states, like New York, have started putting caps on copays, how much a patient pays out of pocket for meds, particularly lifesaving meds like insulin, leaving PBMs, insurance companies and pharma to eat the rest of the cost (as it should be:)

Because as we know, though biosimilars have come out for Sanofi's long-actin basal insulin of Lantus, the price has never dropped, and has in fact gone up.

Why?

Again, varying contracts, with steeper rebates offered for the brand names and "portfolio contracts" where you get discounts on other products by their company if you buy a certain volume of the new drug - mostly to the PBMs especially, my darlings -  which does NOT trickle back down on your insurance premiums or copays.


Sorry, Republicans, but trickle down only works locally and regionally, and even then, it depends on the company - but "trickle down" has never once worked on a national or corporate level.  

You can't give one example of trickle-down ever working at  a national or corporate level, and we can use the cost of pharmaceuticals and healthcare as proof of the opposite -  corporations, and certain C-suite individuals, are too greedy for the market to work properly like that.

I realize that governments can be greedy, too - it's just to act like one is any less greedy than the other is a pointless argument, because you throw the human element of greed into either public or private equation, and neither system alone works well.


Essentially, varying rebate contract deals are why the pharma market doesn't work the way it's supposed to, which is with more products and generics being the biologically similar equivalent, the market price should go down - but it doesn't.

Regardless, back to the interviews, both agree about the prices being outrageous.  


The payer being interviewed on behalf of the insurance company is is usually either their medical director or the pharmacy director.

The medical director is an MD, but who no longer sees patients; typically a former family practice/ internal medicine, but not a specialist.  The pharmacy director likewise no longer practices/dispenses medication.

They always explain why they put step-through restrictions on certain things to the clinician, to avoid automatically paying out millions for the latest, newest, shiniest, possibly just "me-too" thing that doesn't perform any better than what's already on the market, and that hasn't been tried in the real world yet.

The KOLs (key-opinion leaders) are current practicing specialist physicians who have been deemed by medical societies to be experts in their field, often practicing at Centers of Excellence for their disease states - or as pharmacy directors and pharmacists still practicing/dispensing at these institutions, and thus often are pharmacy specialists, i.e., oncology pharmacists.

They explain to the payer why some of these step-throughs are inappropriate in their treatment algorithm, wasting not only precious relief time for the patient, but more money, what they actually see in practice and how it compares to the study, and everybody better understands each other.


And the best result of these combined payer/prescriber marketing interviews, with both payer and clinician, at the same time is -  both come up with a plan on what the treatment algorithm should be, what should be first-line treatment, second-line, etc. that better suits both parties, keeping the other side's goal in mind, better understanding why they do what they do :)


Dang, not only should they do this more, but if Congress could also do these anonymous, double-blinded interviews, too, just imagine what understanding we might gain from the "opposing" sides and what we might accomplish? :)





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