Interesting advice on prescribing from Rev Prescrire February 2013; 33 (352): 138-142. Some things i picked out.

– Injectable promethazine, an antihista- mine used in severe urticaria, can cause cutaneous necrosis and gangrene (Prescrire Int n° 109). Better to use injectable dexchlorpheniramine.

– Iron dextran carries a higher risk of hypersensitivity reactions than other injectable iron preparations (Prescrire Int n° 126).

– Tibolone, a synthetic steroid hormone used for post-menopausal hormone replacement therapy, has androgenic adverse effects, in addition to those of its oestrogen and progestin components (car- diovascular disease, breast and ovarian cancer, etc.) (Prescrire Int n° 111). When a woman opts for hormone therapy despite the risks, it is best to use the low- est-dose oestrogen + progestin combina- tion for the shortest possible time. 

 – Moxifloxacin is no more effective than other fluoroquinolones but carries a risk of Lyell’s syndrome, fulminant hepatitis, and more frequent cardiac disorders (Rev Prescrire n° 327);

 – Duloxetine can cause liver damage (Prescrire Int n° 111);

– Ketoprofen gel carries a higher risk of cutaneous disorders than other topical NSAIDs (Prescrire Int n° 109, 112);

 – Strontium ranelate can cause neuropsy- chiatric disorders and hypersensitivity reactions, including Lyell’s syndrome and Dress syndrome (drug reaction with eosinophilia and systemic symptoms.), and also venous thromboembolism (Prescrire Int n° 125);

DEPP framework for Medical Advisors

I have been spending the last few months training two medical advisers. In the process I realized that there are limited tools for helping medical advisers approach the therapies/devices or situations we face daily. So in the process I came up with a basic framework for assessing/authorizing or advising. I believe its just as relevant to marketing advisory as managed care related reviews.


(D)iagnosis:This should be starting point when looking at any issue. 

• Is the diagnosis certain ?
• Is the diagnosis easily made and what is the gold standard ?
• Does the target provider have the skills to make this diagnosis ? if not why not?
• When this diagnosis is made what factors are generally taken into consideration ?

Tools: Society Guidelines, ICD 10 codes, Review papers, Good understanding of pathophysiology.

(E)vidence:What does the cold hard facts say?

• Is it clinically appropriate ?
• Does the research link the treatment and the diagnosis well ?
• Is this a labelled indication? If not why not ?
• What is the strength and depth of the evidence ? Is there a ongoing trial that might change the whole accepted view?
• Evidence vs Hope?

Tools: Evidence Based medicine reviews, Cochrane, NICE, Society guidelines, Uptodate

(P)rice: How cost effective is it?

• Cost effectiveness reviews  ?
• Is the marker of cost effectiveness relevant ?
• Price vs alternatives ? Item price vs true cost ?
• Affordability on individual/group and population level ?
• QUALY?
• Do we have any data to asses?

Tools: NICE, PBS, Managed Care Policies, Pharmacoepidemiology

(P)olitics: What are the rules and opinions that affect this area?

• Laws and guidelines  ?
• Codes of conduct issues?
• Current political/social climate ?
• Fallout ?
• Client/ Key account issues ?

Tools: Codes of conduct, Google news, Local Laws, Precedent

The move from in-house development to buy-your-tech

Good year to all

I recently did a talk on the study at Northwick Park that was done by Tegenero
and Parexel where 6 of the eight volunteers had severe cytokine storm reactions.

One of the issues that struck me was the relationship between Parexcel and Tegenero.

Over the last two years the wires have been awash with licencing deals between small start-ups like these and big pharma. And if you look at the rate of attrition of R & D departments at big pharma, the trend is likely to continue. Large pharma has even been clubbing together to start venture capital firms that invest in start-ups with a right to licence the technology later.

I agree with the business model, a small focused developer with their acorns in vice to get a product to market will generally beat a large corporation for development re: Peter Drucker.

The issues that in my opinion has arisen from the Nortwick Park study is the following:

1. Trial design and safety

The issue with the trial design and decision to give all the patients the therapy at 10min intervals have been documented before ( Duff Report)

I would have thought that Parexcel as the CRO would have advised the company against such a risky strategy in first in man studies. The possibility exist that Tegenero didn't have the funds for slow multi day escalation study and this is why they did it this way. We all know the results.

So small companies might be forced to cut corners to save money in the development cycle. If large pharma is now a partner, they will expose themselves to these risks that they might not have had if it was done in house.

2. Phase 2 and 3 patient pool reach.

Limited venture capital funds mean that in phase 2b and three a small company would not be able to do a large study of the kind that you now see in cardiovascular medicine.

What this means is that by the stage that your product needs FDA/EUDRA approval you might have to go back and do more work because of limitations in your applications. Further what the development people sometimes miss is that in the marketing of a therapy , indications rule the roost and if you are stuck with a very narrow indication, everybody at Marketing will know what a great drug it is but they may not tell anybody about it.

3. Vested interest

The main goal of any therapy development company is the create something that will help patients better. The smaller the developer the larger the risk of survival overshadowing this imperative.

So when you read about these large licencing deals, know that its a high risk bet, even at phase 2b stage and if you are involved, make sure they will take the same precautions you would have if you developed it in house.

Cheers

The UNk

Sermo mines your personal conversations

I recently received a mail inviting me to buy a report from Sermo, a healthcare physician social networking platform. Mmm I thought, I hope all those doctors knew that their discussions will be mined.

Sermo allows only US doctors on their sites , so I could only read their terms of use and privacy policy. But its pretty clear that they own anything you put on the site and can do with it what they will:

"OWNERSHIP OF MATERIALS

All Materials on this Site are provided by Sermo unless indicated otherwise. All intellectual property rights in the Materials (including copyrights, trademarks, trade secrets and patents) are the property of Sermo unless indicated otherwise. Sermo retains all copyrights in the individual pages, and their components, and collective works available at the Site"

"16. USER SUBMISSIONS

Unless otherwise agreed in writing prior to Your submission, any material, information or other communication You transmit or post to the Site or third party site will be considered non-confidential and non-proprietary ("Communications"). Sermo will have no obligations with respect to the Communications. You agree that from time to time Sermo may invite or otherwise make You aware of certain educational, promotional or financial opportunities relating to Your Communications and profile."

That is unless you as the doctor say anything that sermo gets into trouble for, in that case:

"REPRESENTATION

As a user of this Site, You are liable for the accuracy of the information that You provide to us, including, but not limited to, Your personal and professional representation as provided in Section 4. You hereby certify that You are not a paid consultant or have any other financial interests in the information you provide to this Site including, but not limited to the promotion of "off-label" drug uses, the disclosure of confidential clinical trial or other proprietary information."

So this means that they are constantly monitoring and mining what you ask or say. It would be interesting to know of any lawsuits regarding comments or questions that they made on the site that was later used in a malpractice case.

I hope all the docs who are on their site knows what they have signed up for.

This makes me wonder about all those sub-sites in Facebook. I am sure the same level of mining goes on there, maybe with less protection because those sub areas are sponsored subsites.

So the moral of the story is , no matter where you are big brother and big business and big lawyers are watching , so be carefull.

Cheers

The Unk

Selling a service VS Selling stuff

See my previous post on the issues regarding business strategy that the industry face.

As a follow on, I want to go into more depth regarding the central issue of what a pharmaceutical company should be doing.

I had heard a few years back that Pfizer had a big heart to heart on its strategic future. Should we only sell meds? Should we become a healthcare provider ?

The traditional model appears to be :

1. Find a treatment target
2. Design a treatment
3. Test the treatment
4. Sell the treatment

So pharma saw itself as a manufacturer of commodity goods. This paradigm holds up well as far as revenue is concerned if step 1 to 3 works well. The less successful these are the more money you have to pour in to make it tick. A bit like a house of cards.

A pharmaceutical company is actually three companies in my mind:

1. A manufacturing company
2. A clinical research company
3. A marketing company

Now if you look at AstraZeneca they have been virtualizing their company: Outsource no 1 ( theres a article on fiercebiotech on the topic) Outsource no 2, ie agreement with quintiles and they have been outsourcing Sales to contract sales companies all over the world.

Pfizer on the other hand is trying to solve the problem by doubling the size of 1, 2 and 3 in the hope of more revenue.

Novartis (who i rate the highest by the way) seems to have split their company by the aquisition of Sandoz the generic maker, they then moved step 1 to sandoz and retained 2 and 3 as the core of their ethicals business.

What I would love to see is one of these giants realizing that the model they use is now defunct and do the following:

1. Fully owned contract manufacturing company, keep it in house but make stuff for other people too, dont just get rid of this capcity to the chinese.
2. Research and development company that is run like a biotech and has to make money for itself by in or out licensing
3. A pharmaceutical service company that : supplies all the products in a treatment area ( whether you make it or not), finance support and loans to enable aquisition of medication plud clinical services to back up the formulary( including screening, compliance, audits, IT systems and people) . This means that healthcare providers will outsource treatment in certain therapeutic areas to the service company, except direct clinical decision making.
4. A marketing company that sits appart and supports the ALL of the other three units.

and thats my take on changeing things.

The vested interests that will stop this happening?

• Pharmacies and current middle men
• ABPI and PHarMA cause they are not geared to think this way
• Narrow minded politicians who still havent figured out that interaction does not mean undue influence ( think of something you can smoke if you want to know which senator i am talking of)

Can you see patients complain? Cheaper medication, better service and decisions made on treatment effect not price (cannot afford) or brand name

cheers

Herr Dr UNK

Kearney the Genuis

AT Kearney just published their second report on the future of the pharmaceutical industry (http://www.atkearney.com/images/global/pdf/Pharmaceuticals_Out_of_Balance_2.pdf) .

To me it looks a lot like the PWC report done earlier this year on what pharma has to do to stay profitable ( http://www.pwc.com/gx/en/pharma-life-sciences/pharma-2020/pharma-2020-marketing-the-future-which-path-will-you-take.jhtml)

What keeps astounding me is that they all say the same thing. I mean these guys are paid a lot of money to come up with strategic approaches to help some of the biggest companies.

Yes they contain beautiful pictures and impressive graphs but they seem to add very little to solving the issues that companies face.

Here is Kearney's solution to all our ills (patent cliff, fired reps and efficacy re-imbursement):

"1. Know your therapy areas, and strengthen your market-access and market-development skills to build an intimate understanding of care pathways, stakeholders and drivers for each therapy in each locale.

2. Build a long-term decision-support modelto make difficult trade-off decisions on price, investment, make or buy, therapy and geographic focus—and thus optimize portfolio value. The model should include a clear understanding of the relative profitability of niche or mass market pricing strategies, and a thorough knowledge of emerging low-cost examples. Abandon the U.S.-centric model and adopt a more global view.

3. Put the market back into innovation bycreating mechanisms to align the development portfolio and process with market needs, build relationships between marketers and scientists, align incentives and implement trial processes that operate seamlessly.

4. Set up for success in emerging marketsby localizing development activities, creating

low-cost mass-market solutions, and building relationships with local delivery agents.

5. Get ready for a lower cost model by redesigning the manufacturing and distribution footprint, looking for manufacturing and distribution partners, and preparing for mass production."

So the big solution? More marketing and make stuff cheaper then try all the tricks in the book to find new drugs. Mmm very novel, sounds to me like something from a first year marketing class.

What one should remember is that the pharmaceutical industry has its origins from pharmacist who used to make cures in the back of their shop and then sell it to customers. Some worked , some didnt, but the model has not changed much. Its become more sophisticated and more removed from both the patient and the supply side , but its still the same.

And this is the main weakness of pharma today.

When novelty wears thin, all that is left is price.

What most companies forget to realize is that you are selling blood pressure lowering, not an ACE inhibitor.

That mental switch is a significant one. but more on that on the next post

Monsieur UNK

Brilinta

This is my first post on the new blog. I decided to move away from twitter because of the limited nature of the way you can post. Most of the topics I am interested in require more than a few words.

As the topic of my first post I chose to discuss Brilinta the new anti-coagulant that BMS and AZ have developed. It appears to be one of the few possible block busters out there.

The landmark PLATO (http://www.astrazeneca.com/media/latest-press-releases/brilinta-plato?itemId=5837126) study has been spitting out data at the ECS and the AHA over the past months and now would be a good time to see if all the fuss is warranted.

On face value it beat plavix hands down. Much better outcomes with the same incidence of bleeding side effects. And with plavix beset by all the PPI issues (http://www.webmd.com/heart-disease/news/20090303/plavix-ppi-combo-risky-for-heart-patients) Brilinta seems to waltz into the market at the right time.

I believe that the reason why it was more effective , was also the reason why the marketing of the medication will end up being an issue. The twice daily dosing and the faster onset of action means that the drug keeps a steadier anti coagulation profile at a lower dose according to my reading of the data. It also means that anti -coagulation will reach its required level earlier for those patients that need it right now, ie heart attacks. The stent and ST elevation MI sub analysis seem to bear out this assumption.

As far as the market is concerned , two issues must be uppermost on the minds of the AZ/BMS guys: 1. Plavix is going generic and 2. The twice daily dosing.

Fortunately its shown to be a lot better than Plavix so when they get to NICE or other clinical effectiveness bodies they will have a good case to argue. Saying that , it would probably be shoe horned into the acute coronary syndromes treatment area. For chronic therapy plavix might still win on price. I really hope AZ/BMS will do a genetic sub study for those that are plavix resistant , because in that group Brilinat has a definite chronic indication, same holds for patients on PPI's.

The twice daily dosing is a red herring to me , ace's have been bd for years and cardiovascular patients tend to be fairly compliant on them. Look to the pharma guys thinking of a combo brilinta / ACE inhibitor as a logical development.

I would also love to see a pre-hospital study comparing brilinta with aspirin with suspected ACS patients. With its quick onset it would be ideal for ambulance personal to give , and lets face it not everyone lives 60mins away from a stent.

So watch this space on how the drug will do. But with AZ firing anyone with the word rep on their nametag , I am not sure how they will be able to spread the message quickly to their prescriber market.

Cheers

Comrade Unk

ps: I get paid squat for what I say , so this my unbiased opinion