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June 30, 2008

The Pharmaceutical Past is Prologue

by Peter Pitts

The Wall Street Journal reports that, “Last year, the FDA approved just 19 new medicines, the fewest in 24 years, and announced about 75 new or revised "black-box" warnings about potential side effects -- the agency's strongest -- twice the number in 2004.”

True. But numbers are just numbers. The story is somewhat different when you put those numbers in perspective.

According to the Journal story, “Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, denies that the agency has become "more conservative" about drug safety. Rather, she says, the industry's faltering research efforts are mostly to blame for the fewer product approvals. She says the agency continues to base its decisions on science, not outside pressures. New methods, she adds, have helped it become more vigilant about side effects. She attributed the increase in black-box warnings primarily to a few large groups of medicines that were relabeled."

Reality bites.

Bringing new drugs to market has always been a scientifically challenging and expensive proposition – and it remains so. But the big difference today isn’t (gasp!) politics – it’s that, while discovery and development embrace 21st century science, regulatory science lags behind. At present, the FDA is using 20th century tools to review 21st century medicines.

This is why the agency’s Critical Path Program and the Congressionally-mandated Reagan/Udall Foundation are so crucial to our 21st century healthcare future -- as well as to the future of the pharmaceutical industry.

The comments of Schering-Plough CEO Fred Hassan (courtesy of the Journal article) are instructive:

“Mr. Hassan believes an intensifying focus on safety and a diminished tolerance for side effects at the Food and Drug Administration have dramatically lowered the odds that the drugs would make it to market -- at least not without a lot of extra time and money.”

Not so fast. It is today as it has been in the past and must be in the future – the quest for appropriate risk/benefit balance. Side effects are “tolerated” insofar as the benefits are appropriate. As to the “extra time and money” comment – there’s no benefit from wishing for the “good old days.” Time marches on and so does science. Perhaps a better focus would be on more innovative clinical trial designs – and on the FDA’s promised guidance on adaptive clinical trial designs.

The past is prologue.

"What will it take to get new drugs approved?" Mr. Hassan asks. "The point is, we don't know."

Yes we do. Better development science and better regulatory tools for the FDA.

Posted by peterpitts at 10:06 AM
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June 26, 2008

Repack Attack

by Peter Pitts

pharmaceutical industry in Europe is calling for a ban on the repackaging of medicines within the European Union in order to stamp out the growing threat of counterfeits.

This is not a new idea – but it’s a good one. But it’s often derided as the pharmaceutical industry calling for a policy change for reasons of self-interest rather than public health.

But at the recent BIO convention in San Diego a European Commission representative said that Brussels is seriously considering proposals that would ban repackaging – a move that, if taken would (according to Reuters), “deal a blow to the parallel trade and could also help drugmakers' profits, since companies' revenues are currently eroded by arbitrage dealings in their products across borders.”

Does this mean that the European Commission is in the “pocket of Big Pharma?”

Hardly.

(In fact, it’s humorous considering the way the industry is treated over there.)

What it does mean is that, enfin; the EC is taking seriously what we here at drugwonks.com have been saying for some time – that parallel trade is the weak link in the pharmaceutical chain of custody and a prime target for counterfeit infiltration.

It’s also important to note that what the Europeans call “parallel trade,” we refer to as “importation.” And that Canadian Internet pharmacies get their drugs from Europe. (Note: over 20% of all pharmaceuticals legally sold in the UK are parallel traded into that island nation from other nations within the EU such as Greece, Latvia, Portugal, and Malta and often illegally from places such as Russia and Turkey.

“Safe” importation?

Perhaps in a parallel universe.

Posted by peterpitts at 01:29 PM
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June 23, 2008

Must see TV, eh?

by Peter Pitts

According to PharmaTimes, CanWest Mediaworks, Canada’s largest newspaper publisher and owner of more than 30 television stations, is suing the federal government for not permitting direct-to-consumer advertising of prescription drugs because, it says, this breaches its freedom of expression under Canada’s Charter of Rights and Freedoms.

CanWest is arguing in the Ontario Superior Court that this prohibition, which is part of the Canadian Food and Drugs Act, places it at a competitive disadvantage to US newspaper and magazines which are sold on Canadian newsstands, because it prevents it from selling advertising space to pharmaceutical manufacturers. The company also points out that Canada does allow OTC medicines to be advertised directly to consumers, even though these products also carry risks.

The case will be heard this month.

Posted by peterpitts at 08:18 AM
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June 19, 2008

BIO Break

by Peter Pitts

There’s so much going on at the BIO convention. It’s a healthcare policy feast.

One panel I attended was on the future of personalized medicine via diagnostics. A few of the points made were:

* At present, “trial and error medicine” is the standard of care. Not good for providers, patients, nor payers. That’s true.

* What we today call “personalized medicine” will be referred to in the near future as “medicine.” That’s hopeful.

* Diagnostics will deliver personalized care via drug selection, dosing, efficacy, disease status, recurrence risk, and predisposition. That’s exciting.

* Diagnostics lead the league in the price/value proposition – and that’s what will initially drive uptake. That’s reality.

* To that point, there was also discussion of a diagnostics acceptance continuum beginning with “fear” and then moving to “value” and finally “acceptance.”

* And the constituencies moving along that path include pharmaceutical companies, physicians, patients, payers – and regulators.

* Specifically, to more expeditiously sashay down the Critical Path, the diagnostics industry needs industry-wide guidelines for clinical research.

Take-away is that "personalized" medicine is 21st century medicine. And that's a "win" for physicians, payers ... and even patients. As BIO Chairman (and Vertex CEO) Dr. Joshua Boger commented at the opening day's keynote, we must all be "a confederation of optimists."

Posted by peterpitts at 11:01 AM
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June 16, 2008

Stipulating Bias

by Peter Pitts

According to a new editorial in the Lancet, “From February to April this year, the European Commission (EC) held a public consultation on proposed legal changes that would allow pharmaceutical companies to provide information to patients about prescription-only drugs via all available media. The Commission's proposal states that the ban on direct-to-consumer advertising (DTCA) in Europe would remain. However, many critics rightly feel that allowing the industry to provide information to patients is effectively DTCA under a different name.”

Who are these critics? What are the agendas? Where does their funding come from? On these questions the Lancet is silent.

The Lancet opines, “Patients' access to quality information is variable across the European Union's 27 member states and the Commission is right to want to address this inequality. But the pharmaceutical industry's obvious financial conflicts of interest mean that drug information provided by them is likely to be prone to bias.”

“Likely to be biased?” On what do they base this rather strong statement? Isn’t solid, unbiased information in the best interests of both sales and the public health? Isn’t there a more inherent “bias” by having payers control what information consumers get to see? And in the EU, “payers” = “government.”

The editorial concludes, “Patients have a fundamental right to access good quality, objective information on medicines. The EC's final proposal, due out later this year, must empower patients and not the drug industry.”

Why not empower the drug industry to empower patients? That’s what the pending EC directive is all about.

And as far as the Lancet stipulating bias, consider the words of Robert Benchley:

"Tell us your phobias, and we will tell you what you are afraid of."

Posted by peterpitts at 08:20 AM
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June 10, 2008

Money talks? Healthcare walks.

by Peter Pitts

Last week I attended a conference of European pharmaceutical executives, legislators, and regulatory officials. The theme was “Economics and Ethics.”

While the “universal” consensus was that ethics are primary – economics came in a very close second. One robustly debated theme was the idea of “an ethical standard based on resources.”

In other words, reality.

We live in the real world where increasing drug development costs and shrinking resources for reimbursement (government-paid in the case of the Europeans) cannot be ignored when it comes to either green-lighting a development program or making an access decision based on healthcare technology assessment (HTA).

One leading consultant suggested that pharmaceutical development program should not proceed beyond Phase II until the company met with reimbursement agencies to gauge the likelihood of a positive coverage decision based on clinical endpoints.

Frightening that such a highly paid consultant could so completely miss the point – that government healthcare systems exist to serve their citizens, not to act as actuarial bean counters. Financial prudence? Cetainly. But not at the expense of the right medicine for the right patient at the right time. That’s a medical decision. That’s ethics.

Many present pointed out that what we really need are better tools to allow smarter development programs that don’t fail in late Phase III (as over 50% do today). In the US that means the Critical Path. In Europe it’s the Innovative Medicines Initiative. Both are predicated on patient-centric care.

But when a healthcare system is a government-pay model, the cost-based versus patient-centric momentum seems unstoppable.

Consider the remarks last week of Thomas Lonngren, executive director of the European Medicines Agency (EMEA),

"It could come to a situation where we are approving a product based on efficacy, safety and quality ... but the patient can't get it because the health technology institute says it is not cost-effective."

Note to Tom – already happening.

Consider Britain's National Institute for Health and Clinical Excellence (NICE) and the series of high-profile disputes in which new drugs for conditions such as cancer and rheumatoid arthritis have been turned down for use on the state health service.

And what’s worse than a bad decision in one country? Correct – a cavalcade of uncoordinated, voodoo cost-based decisions -- with one even less patient-centric than the last. Or, as Lonngren commented,

"… a different decision in each member state (of the European Union) because this is not harmonized.”

Other countries, including Germany, have recently set up their own versions of NICE and
Lonngren said the emergence of such health technology institutes posed a challenge for drug manufacturers since these bodies often required additional research, and he suggested there might be scope for cooperation with the EMEA in designing drug approval programs in future.

Is that a good idea, EU harmonization of HTA? Or is it the camel getting its nose under the tent?

And that, dear readers, is the distinction between “universal” healthcare and “government” healthcare. In short –no difference at all.

Posted by peterpitts at 08:49 AM
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June 09, 2008

The Counterfeiting Superhighway

by Peter Pitts

Last week, in Washington DC, I spoke at the Fourth Global Forum on Pharmaceutical Anticounterfeiting. My talk was why we won’t see legalized drug importation after the November elections – regardless of who gets elected.

There are four basic reasons:

1- It won’t save any money.

2- The drugs being sent to U.S. customers from Canadian Internet. pharmacies are not “the same drugs Canadians get.”

3- The state experience has been dismal and politically embarrassing.

4- National Security concerns.

(For more detail on these points click here:

http://www.drugwonks.com/blog_post/show/5011

Adding fuel to the reality is a new report just made public at the conference, by the European Alliance for Access to Safe Medicines (www.eaasm.eu). The title says it all, “The Counterfeiting Superhighway.”

The report reveals the scope of the unregulated trade of fake pharmaceuticals. Through extensive research and examination of over 100 online pharmacies and over 30 commonly purchased prescription-only medicines, the report makes one thing very clear – we’re not winning the battle.

Key findings from this report

• 62% of medicines purchased online are fake or substandard (including medicines indicated to treat serious conditions such as cardiovascular and respiratory disease, neurological disorders, and mental health conditions).

• 95.6% of online pharmacies researched are operating illegally.

• 94% of websites do not have a named, verifiable pharmacist.

• Over 90% of websites supply prescription-only medicines without a prescription.

• 78.8 of websites violate intellectual property.

My favorite anecdote is the report’s example of an Internet pharmacy whose products came wrapped in pages from the Mumbai Daily News. The most frightening fact, though, is most of the fake medicines “were delivered in seemingly authentic boxes, accompanied by patient information leaflets in good condition and ostensibly trustworthy blister packs.”

The report concludes by providing recommendations based on the research findings and calls all stakeholders including search engines, credit card companies, shipping companies, patient groups and regulators, to take action and halt this dangerous trend.

Bravo.

The full report can be found at:

http://www.eaasm.eu/Media_Centre/News/The_Counterfeiting_Superhighway

Drug importation is not on their list of solutions.

The take-away for U.S. electoral rhetoric is obvious – Senator McCain and Senator Obama cannot be for enhanced drug safety and for drug importation. It’s simply does not compute.

Posted by peterpitts at 12:16 PM
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June 02, 2008

"Page" Turner

by Peter Pitts

A few weeks ago I was on a panel with J. Rick Turner, Chairman of the Department of Clinical Research and Director of the Cardiac Education Center at the Campbell University School of Pharmacy. And, as usual, the most interesting part of the conversation happened after the panel was over.

As we were gathering our papers and checking our blackberries, Dr. Turner mentioned that he had written a new book on the issue of “integrated cardiac safety.” I asked him to send me an advance copy. And he did.

They don’t call him “Page” Turner for nothing.

His new book, “Integrated Cardiac Safety: Assessment Methodologies for Noncardiac Drugs in Discovery, Development, and Post Marketing Surveillance,” is a timely and important addition to the debate over drug safety and, equally important, safe use.

Consider the following brief excerpts:

“A drug’s development in the sense of improving its safety and/or effectiveness profiles does not stop at the point of marketing approval. Data collected during the drug’s use in large patient populations can lead to meaningful improvements in the drug. This term, lifecycle drug development, therefore emphasizes that it is vital to remain vigilant about the drug’s effects from the very beginning of the drug discovery phase throughout the entire time that the drug is on the market and hence available for prescription to patients, and it captures the spirit of this book very well.”

“So too does the term integrated cardiac safety. A central tenet of this book is that it is beneficial to discuss the assessment methodologies used to collect information on cardiac safety at four stages of lifecycle drug development—drug discovery and design, nonclinical development, preapproval clinical development, and postmarketing surveillance—in one book, and to integrate this information to the greatest degree possible.”

“Meta-analyses vary in the number of patients included since this is dependent on the numbers in the individual trials combined in the new analysis. However, typical numbers are also in the thousands. However, it is fair to say that statistical methodology is currently less well developed in the case of epidemiology studies than it is for randomized controlled trials: this is not meant as a pejorative statement, simply a statement of the current state of affairs that will hopefully and very likely change as additional spotlights on and developments in the field of pharmacoepidemiology increase.”

“It should also be noted here that the term nonexperimental is not a pejorative one compared with the term experimental. Piantadosi discussed two fundamental types of study design, experimental and nonexperimental. In experimental studies participants receive random treatment allocation, and observations are made under conditions in which the influence of interest is controlled by the research scientists. In nonexperimental studies the research scientist also collects observations but does not exert control over the influences of interest. Nonexperimental studies are often called ‘observational studies,’ but this term is inaccurate: it does not definitively distinguish between nonexperimental studies and experimental studies, in which observations are also made.”

The book, due out in November of this year is must reading – especially for Steve Nissen.

Posted by peterpitts at 07:54 AM
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