Category Archives: Critical Consumer

How Antibiotics Work

Antibiotics work according to the mechanism of action (what the drug “targets” in microbes or how the drug “works” in the microbe) that is driven by the drug’s distinguishing chemical structure.

Chemical structures also define the “classification” of antibiotics. If you hear doctors talk about “macrolides” versus “quinolones”, they are talking about families of drugs (not “one” specific drug) and they are referring to the way each family of drugs targets microbes.

When you hear about “generations” of an antibiotic, this means the chemical structure of the current drug has been modified (changed) somehow. These changes are designed to improve the action of the drug, especially when the bacteria have evolved to resist the original drug.

A well known example is Penicillin resistance. Overuse of penicillin resulted in widespread bacterial resistance to this drug. If I went to the doctor today and the doctor decided that a beta-lactam based antibiotic was appropriate, the doctor may prescribe amoxicillin or one of the newer generation cephalosporins versus the original penicillin. That’s because the doctor is thinking the bacteria in my body will probably laugh at penicillin and a “newer” penicillin (like amoxicillin) may be needed.

Why We must complete the ENTIRE course of antibiotic therapy

One of the biggest problems in antibiotic resistance, besides antibiotics being over-prescribed, is patients stopping their medication as soon as they start feeling better instead of finishing their entire course (taking ALL pills prescribed by the doctor).

Imagine your body is a kingdom and your immune system as a fortress/defense system. Your kingdom has undergone an invasion. Taking antibiotics is similar to giving your immune system a much needed weapon to defeat the invaders.

A full course of antibiotic therapy aims to kill off as many invaders that have infiltrated your kingdom within as short amount of time as possible, so that your defense system can take care of the rest, and to ensure that ALL the invaders are killed.

People sometimes stop taking the antibiotic when they start feeling better (“Oh, I’m already feeling better”) or for another reason (“hey, maybe I should save these couple of pills, just in case, for next time”). The problem is that there may be a few invaders that have thus far evaded the antibiotic response, and these will be the invaders who will come back with a vengeance, literally.

Your feeling better has do to with most of the invaders being killed off, but the few that have escaped being killed are buying time to adapt and evolve… to become smarter against your defenses.

Antibiotic resistance arises from the ones that have been allowed to escape because the host (you) decided “All is well, call off the troops!” and giving the invaders time to learn how to better take you down the next time there is an opportunity.

Based on the way each antibiotic family targets microbes, the drugs in that antibiotic family may either kill (bactericidal) or stall the growth of (bacteriostatic) microbes.

This is where we get into the specifics of “how” an antibiotic works. Antibiotics aim to kill by:

  • Targeting a specific feature of bacteria
  • Targeting the reproductive process of bacteria
  • Targeting a critical chemical pathway in bacteria (especially protein synthesis)
  • Overcoming bacteria’s evolved mechanisms of resistance (for example, bacteria that have evolved pumps in their membranes to “pump out” drugs)

Targeting a Specific Feature of Bacteria, Reproduction, or critical process (typically making proteins or “protein synthesis)

Antibiotics that target gram positive bacteria will disrupt the chemical process critical to making the thick peptidoglycan wall (the thick wall is what holds the “gram stain” that allows us to visually identify the “gram positive” bacterial strain).

However, if the bacteria has a thin peptidoglycan wall (this then won’t show up as bright violet stains on the gram stain, making this bacteria a “gram negative” type), then an antibiotic that targets that wall won’t do much damage.

Instead, you’d need an antibiotic that targets a specific feature of gram negative bacteria or target a critical process like protein synthesis. For example, the antibiotic can cross the gram negative bacteria’s cell wall (but are blocked by gram positive bacteria’s peptidoglycan layer) to stop protein synthesis, which stops many critical machinery in bacteria.

Antibiotics that target the bacterial reproduction prevents new bacteria from being produced. This gives your body a fighting chance to go over the existing microbes.

Dream and Nightmare of Web-Scale Pharmacovigilance

I’m not going to tap into fear-mongering of why Microsoft is involved in the study that pulls adverse event (side effect) data from the internet, but I’m wondering what’s taken people so long to figure out the vast pool of patient experiences available online. Oh wait, those of us involved in industry know about this, only we don’t want to know about it.

There is at least one valid reason: you need to have a full picture of what is involved behind a side effect, to say with some level of confidence that your reported side effect experience came from the drug you said you took, not the other drugs you’re conveniently not saying you’re taking (especially the not-so-legal kind), or that you have a drinking habit (alcohol has major interactions with every drug under the sun), or that you’re taking 20 supplements you got from the nutritional store, and some prescription med you got off the internet by some shady doctor who asked you a few questions before writing you the Rx…

But reality check. Web-scale pharmacovigilance is here, and needs to be here, and should be leveraged conscientiously and systematically.

2013-03-10 09.16 AM74

Some years ago I gave a talk at a DTC conference in New Jersey about the patients’ voice when it comes to safety information. I am not in the business of web-based pharmacovigilance, nor did I set out to collect this information, but patients started sharing their personal experiences with an antidepressant on my mental health website. Yes, there are paroxetine/Paxil-related reports, but for the most part patients talk about bupropion/Wellbutrin, and over the span of many years there are hundreds of patient reports that are consistent in terms of their side effect experience.

This all started with one reader asking a question about a particular side effect of bupropion, and whether there were any published studies about a particular side effect. I’m sure there are scores of data from the manufacturer, but like much of drug data, these are kept “proprietary” with the ever-present “data on file” label on clinical slide presentations that the manufacturer supplies to a well-selected public (doctors).

Industry shouldn’t fear it or revile it: pharmacovigilance is critical for gathering drug information over time as part of safety monitoring, and the FDA sucks at making this an easy task for anyone with the desire to report adverse events with bureaucracy.

Read NYT’s take on web-scale adverse event reporting and drug safety monitoring.

Patient Hot Buttons in Pharma: Absurd Advertising

Series with Casey Quinlan

Absurd Advertising (Lyrica + Cymbalta for example) that make potent meds seem like something for a rainy Monday.

We in pharma have only a limited (less than 1 minute) of air time, and part of our challenge is to combine increase in awareness of something that used to be seen as “fault of the person” (i.e. depression as a character flaw, not a medical problem) with usage/safety. So it comes across as if we’re making light of the potency of med — obviously we like our meds to be potent so they get approved and look better than our competition — but we also are balancing this perception of “potency = seriousness of my condition, and I want to deny that I have a problem.” How do we improve this balance without turning off people we can truly help?

I don’t see this as a TV-only issue at all – the wide array of advertising, particularly in print and online, are in many ways both more annoying (how many pages will I have to turn in this mag before this drug ad ends?) and a huge waste of company $$ (I know that the lawyer’s chorus of massive small print is FDA-required). What’s the ROI on an ad that no one looks at?

This is true. I will look at only the 1st page of the ad and pretty much ignore the other 30 pages (I’m exaggerating, it’s a bit less than 30 pages…) but yes, pharma companies cannot print only 1 page, they’d love to, but they can’t, because of the requirement to include key data and safety information as mandated by the FDA. I think this is the FDA’s conspiracy to empty drug companies’ coffers through expensive advertising that no one looks at, which counteracts the FDA’s original intent of having patients and consumers exposed to fair balanced (safety especially) information, because no one will look at the whole ad to get the balanced picture.

continued in the COMMENTS portion — jump into the fray with us!

Patient Hot Buttons in Pharma — Series with Casey Quinlan

Introduction: I met Casey Quinlan in October 2011 when we both presented at a Digital Pharma industry conference hosted by DTC Perspectives. Casey describes herself as a “rabble rouser”, and of course, I cannot resist. This is a series of conversations with Casey on various “Patient Hot Buttons in Pharma” that we will be relay-blogging.

Casey

Jane

Segments of this Series:

Absurd Advertising

Lack of Transparency

Behind the scenes manipulation we sense but can’t see

Lack of Presence

Cost

Vaxil Cancer Vaccine Hardly a Breakthrough

I’m not going to exhaust too much research time on this. But I’ll address specifically the article claims.

Again, as with my answer to Are the hospitals known as The Cancer Treatment Centers of America really effective? I will give the company itself the benefit of the doubt, because this was not an official press release put out by the company. Instead it is an article posted in blog format by an non-medical/healthcare organization.

Still, here’s red flag #1:

“It’s a really big thing,” says Levy, a biotechnology entrepreneur who was formerly CEO for Biokine Therapeutics. “If you give chemo, apart from the really nasty side effects, what often happens is that cancer becomes immune [to it]. The tumor likes to mutate and develops an ability to hide from the treatment. Our vaccines are also designed to overcome that problem.”

Putting aside my bias against describing a cancer vaccine as “a really big thing” (this could be a language issue) — Levy, who is the company’s CFO (where is the chief medical / scientific officer? Medical director? Why aren’t they being quoted?) — attempts to describe the evolution of metastasis that then leads to a false claim (if he were in the U.S. governed by FDA’s mandates.)

There is no data from the company that suggests the vaccines were designed to “overcome that problem” — and which problem, exactly? The “immunity” problem? The “mutation” problem? The “ability to hide from treatment” problem? Each of these could be specific traits to a cancer cell, or according to Levy, would collectively describe one cancer cell. These can also be traits for either solid tumors or liquid tumors. But Levy is vague, when the investigational drug is being targeted for development against multiple myeloma, a blood cancer (liquid tumor.)

Red flag #2 Claim of “Breakthrough”

Is this “breakthrough” describing the idea of using a vaccine against cancer? No: Cancer vaccines aren’t a breakthrough. The immunotherapy concept has been around for decades. http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines
Is this “breakthrough” describing the application of the vaccination concept against a specific cancer, namely multiple myeloma? No: As of November 15, 2011 there are 16 different cancer vaccine trials actively targeting multiple myeloma (Vaxil Bio’s trial is listed too). http://www.cancer.gov/clinicaltrials/search/results?protocolsearchid=6406649
Is this “breakthrough” describing a novel target? No: The MUC1 gene has been described back in 1984 when it was first observed in human breast carcinomas: http://www.ncbi.nlm.nih.gov/pubmed/6094338?dopt=Abstract&holding=npg
Is this “breakthrough” describing a particular characteristic of the investigational target? Maybe: According to the company’s website: “Unlike other vaccines which target the entire MUC1 protein or other domains, ImMucin does not contain any non-specific epitopes, which could dilute and disturb specific anti–cancer immunity. ImMucin™ was shown to selectively be expressed on tumor cells, thereby ensuring specific anti-cancer activity.” http://www.vaxilbio.com/index.php?option=com_content&view=article&id=18&Itemid=27

In conclusion:

Hardly a breakthrough,
may be an interesting agent to add to the mix in a cancer that currently has multiple therapeutic options (including antibody-based therapies considered as “novel” agents — see http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001609/),
with limited clinical trial involving more than 15 patients in one site http://www.vaxilbio.com/index.php?option=com_content&view=article&id=24&Itemid=37

Free advice for the company: I’d save the big claims language until I see progress free survival and overall survival data…. because isn’t a true breakthrough grounded in patients getting the outcomes that matter the most to them — an acceptable balance between extended quantity of life with a reasonable quality of life?