The cover of this week’s Economist magazine caught my eye because this weekend I was talking with people about stem cell issues in the context of the Presidential election.

Part of our discussion was how the selection of Sarah Palin as John McCain’s Vice Presidential nominee will effect the Republican ticket’s position on stem cell research.

Doing a quick search on the internet, it appears that John McCain is refining in his position to support research on adult stem cells, while maintaining a foundation that doesn’t alienate the conservative base of his party.  Specifically, the only reference to stem cell research that I could find on the campaign’s web-site is:

Addressing the Moral Concerns of Advanced Technology

Stem cell research offers tremendous hope for those suffering from a variety of deadly diseases - hope for both cures and life-extending treatments. However, the compassion to relieve suffering and to cure deadly disease cannot erode moral and ethical principles.

For this reason, John McCain opposes the intentional creation of human embryos for research purposes. To that end, Senator McCain voted to ban the practice of “fetal farming,” making it a federal crime for researchers to use cells or fetal tissue from an embryo created for research purposes. Furthermore, he voted to ban attempts to use or obtain human cells gestated in animals. Finally, John McCain strongly opposes human cloning and voted to ban the practice, and any related experimentation, under federal law.

As president, John McCain will strongly support funding for promising research programs, including amniotic fluid and adult stem cell research and other types of scientific study that do not involve the use of human embryos.

Where federal funds are used for stem cell research, Senator McCain believes clear lines should be drawn that reflect a refusal to sacrifice moral values and ethical principles for the sake of scientific progress, and that any such research should be subject to strict federal guidelines.

I also found other articles and analyses concerning his earlier positions on stem cell research which seem less equivocal than his current campaign position.

Q: Would you expand federal funding of embryonic stem cell research?

A: I believe that we need to fund this. This is a tough issue for those of us in the pro-life community. I would remind you that these stem cells are either going to be discarded or perpetually frozen. We need to do what we can to relieve human suffering. It’s a tough issue. I support federal funding.

Retrieved from http://www.ontheissues.org/Social/John_McCain_Abortion.htm

Source: 2007 GOP primary debate, at Reagan library, hosted by MSNBC May 3, 2007

New Ad
Our weekend discussion also turned out to be a bit prescient, since my internet search turned up information about a new radio ad the McCain-Palin campaign is running that touts all the benefits of stem cell research without making any qualifications about what types of research would be allowed, or any of the moral issues raised on his campaign’s web-site.

Stem Cells Probably Not a Defining Campaign Issue
While stem cell research is certainly a sub-issue of the abortion/choice debate, and would not likely be a deciding factor for many voters, it is an issue of particular interest for biomedical researchers and some patient groups concerned with the development of better treatments and cures for cancers, (as discussed in the Economist), and degenerative diseases like Parkinson’s and Alzheimer’s.  It will be interesting to see how this issue plays out in the next few weeks and if it is raised during any of the debates…. Stay tuned.

With two notable government actions in the last couple of weeks there has been significant movement towards increasing the use of e-prescribing.

DEA Proposed Rule
The Drug Enforcement Agency (DEA), proposed regulations on June 27th that would make it possible for controlled substances to be prescribed electronically. Interestingly, this was released right after a National Journal article on this topic.

The DEA’s proposed rule is very important, because while it is appropriate to place stronger safeguards on medicines that are likely to be abused (which is the criteria for being a DEA scheduled medicine), having controlled medicines prescribed by pen and paper while all other medicines are e-prescribed would be a logistical problem and obviate many of the potential benefits of e-prescribing.  And technologically, if banks and others can provide secure login systems and other security measures, I would think that e-prescribing systems could be similarly secure to make sure that unauthorized people aren’t electronically writing themselves prescriptions for thousands of narcotics pills using a legitimate doctor’s DEA number.  (See more about this in the e-quackery section below.)

Medicare Bill Contains Carrots and Sticks for E-Prescribing
The Medicare bill which passed Congress yesterday included a provision to increase the incentives for physicians to use e-prescribing technologies.  These incentives are a small percentage add-on to allowed Medicare charges for physicians who are e-prescribing starting in 2009, and a cut to payments for allowed Medicare charges starting in 2011 for physicians who are not e-prescribing.

Movement in a Good Direction
Together these actions move the US healthcare system towards greater e-prescribing, something that if done right, should increase efficiency (with lower administrative costs), and improve quality of care and patient safety by creating a better system for detecting and preventing adverse drug reactions from known drug allergies and drug-drug interactions.  The use of computerized prescription order systems for patients in hospitals has been shown to accomplish both of these improvements, but how e-prescribing will work in the outpatient world remains to be seen.

Challenges to Making E-Prescribing Increase Efficiency and Improve Quality
There are many challenges for e-prescribing in clinicians’ offices.  Like electronic medical records, they have to buy and install the systems, learn how to use them, and then keep them updated – since new prescriptions keep getting approved etc.  Because of these challenges, it is estimated that only about 6-7% of physicians’ offices are currently using e-prescribing systems.

Optimally e-prescribing systems should be an integrated part of the office’s electronic medical records system so that it could identify potential problems with drug allergies, or the need to alter dosages for patients with impaired kidney or liver function.  And at a minimum, a free standing e-prescribing system should be able to keep track of each patient’s prescriptions to flag drug-drug interactions, otherwise it may become nothing more than a sophisticated fax machine – which some could argue (but I wouldn’t) is a rudimentary form of e-prescribing.

While, e-prescribing systems should provide alerts about drug-drug interactions,  potential allergic reactions, and the need for dosing adjustments, systems that constantly flash up reminders for such things when they’re not relevant, leads users to ignore them altogether. I take a lesson about this hazard from my brother who works on designing aircraft information systems. Clearly pilots need to know certain things at the right time, but I doubt any pilot would fly better or more safely if they kept getting an alert about it being unsafe to land the airplane because the wheels were up – even with the plane at 30,000 feet.  OK – that may be a bit of an extreme example, but if the e-prescribing system doesn’t know anything about the patient, it may send similarly useless alerts and lead those using it to ignore all alerts – which could be worse than having no alerts at all, since it having them pop-up and be ignored could provide a false sense of security.

This illustrates what most people involved with healthcare reform recognize - improving the quality and efficiency of healthcare in the US requires making the systems work better since our practitioners are generally already pretty good.  But giving these good people flawed systems won’t help them, their patients (i.e. us), or our overall healthcare system.

This brings me to one last point.  How many e-prescribing systems will each clinician’s office need?  I certainly hope that every pharmacy chain/group won’t require their own version of an e-prescribing system, nor will each payer, insurer or regulator require a different electronic or paper output of the prescription information for reimbursement or quality auditing purposes.  If that becomes the case, then e-prescribing will face even greater hurdles.

Since they do good work in this area, I also want to include the eHealth Initiative’s  summary of the challenges for e-prescribing systems:

• Financial burdens – Physician practices face varying financial burdens related to e-prescribing, including covering the implementation, training and maintenance costs.
• Workflow changes and change management – Although e-prescribing efficiencies and time savings are gained in the long run, introducing e-prescribing, and electronic health records (EHRs), can be difficult, time consuming, and requires adequate planning, training, and support, particularly in the beginning.
• Continued needs for greater connectivity – The infrastructure exists for connectivity among pharmacies, physician practices, payers and pharmacy benefit managers (PBMs), but some pharmacies, payers/PBMs and mail order pharmacies are not yet connected.
• Medication history – Although e-prescribing is an improvement over relying on paper medical records and patients’ memories, the information that is available may not always be comprehensive or accurate and therefore tools to adequately reconcile medication histories from multiple sources are needed.

E-Dispensing – Bad!!  And E-Quackery – Bad Too!!!
One of the other challenges for e-prescribing may be the practical and policy interactions between physicians’ e-prescribing and internet sites that sell medicines directly to a patient without a prescription.  While e-prescribing potentially can improve efficiency and quality, e-dispensing can lead to bad fiscal and clinical outcomes from patients getting fake, adulterated or dangerous pills and potions.

Information on the worst examples of e-dispensing is in a recent report from Columbia’s National Center on Addiction and Substance Abuse (CASA).  Their recent annual report found that the number of web-sites selling controlled medicines without a prescription has decreased from the start of 2007 to the start of 2008 - from 581 to 365.  The CASA report also found, “Of those sites not requiring prescriptions, 42 percent explicitly stated that no prescription was needed, 45 percent offered an “online consultation,” and 13 percent made no mention of a prescription.”

I’m not sure if anyone knows what the total number of patients using these sites is, or the number of prescriptions they are filling, so it’s unclear if this reduction represents a real decline in the “industry,” or just its consolidation and maturation.  What CASA also found - and that I find especially worrisome - is “an emerging practice of Internet sites selling prescriptions for controlled drugs that can be filled at local pharmacies. The report also found sites selling online “medical consultations” which enable Internet users to get controlled drugs online without a proper prescription.”  I call this e-quackery, because this is physicians acting inappropriately, or non-physicians acting in the role of a physician and practicing medicine without a license by writing prescriptions.

Other notable findings from the CASA report include:

• Of the few sites that require prescriptions, half permit the prescription to be faxed, allowing significant opportunity for fraud.
• Benzodiazepines (like Xanax and Valium) continue to be the most frequently offered drugs for sale with 90 percent of sites selling them; followed by opioids (like Vicodin and OxyContin) at 57 percent of sites, and stimulants (like Ritalin and Adderall) at 27 percent of sites.
• According to DEA estimates, in 2007 eleven percent of prescriptions filled by traditional pharmacies were for controlled substances compared to 80 percent of prescriptions filled by Internet pharmacies.
• There are no controls blocking access to these sites by children and teens.

Conclusions
Just to bring things full circle – clearly e-dispensing and e-quackery are bad, so perhaps the greater use of legitimate and appropriate e-prescribing will help to clamp down on these illegal and dangerous activities.  And from a personal perspective, I can also only hope that it will reduce the ongoing flow of spam emails for on-line medicines - and the similar onslaught of spam blog comments to this blog that you never see because I delete them, but which like spam emails, just chew up time from every day.

p.s. Sorry about the long post – but this is an important and complicated topic.

The FDA announced today that they have sent letters to 25 companies to stop selling fake cancer cures. That is, things that the companies claim cure cancer, but have never been tested, or approved by the FDA. The FDA has a web-site with more information about this, and a sub-page that lists 125 Fake Cancer Cures.

I know the FDA gets lots of flack for not doing enough - and not doing it fast enough - I applaud the FDA for taking this action, and encourage them to do more because I have found the advertisement and selling of these non-medicines troubling for a long time.

Cancers are serious diseases by anyones definition, and real medical science is making great strides in developing better treatments and cures, and in overall improving the lives of people living with cancer - both through traditional drugs and biologics, as well as with complementary therapies. But those profiting from selling fake medicines are selling false hope.

I would like the FDA go after more of these people who are profiting from selling fake medicines marketed as cures for other diseases and conditions - particularly ones that may be for symptoms of serious conditions. For example, every time I see the plastic-faced grinning guy on TV hawking a non-FDA approved “natural male enhancement” product, I wonder about all the men who may still be too embarrassed to talk to their physician about their erectile dysfunction problem - which unknown to them is being caused by a serious medical problem, like cancer. And of course for men who are buying this stuff who don’t have ED, then it would be nice if they could talk to their physician about therapy to address the route causes of their feelings of sexual inadequacy.

But of course, the FDA currently has insufficient resources to cover all of it’s multiple priorities - which is why Congress and the Administration are discussing how to provide more funding. Until that happens, I hope the FDA continues being vigilant and stops as many of these purveyors of false hope as they can - at least so these people don’t get the idea that because the FDA’s resources are stretched a bit thin, that the FDA won’t bother them.

The FDA announced yesterday that both the FDA and the European Medicines Association (EMEA) will accept seven biomarker tests for early kidney damage. These animal based tests were developed by a public-private collaborative and will be a voluntary part of the regulatory applications for new drugs. However, it is believed that companies will benefit by doing these test because they will both be able to detect toxicity problems earlier in a drugs development, and enable the approval of more powerful drugs, “because health care professionals could closely monitor patients and halt the drug if early signs of renal toxicity appear.”

“The development of these and other biomarkers can result in important tools for better understanding the safety profile of new drugs,” said Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research. “We hope these biomarkers will lead to human tests that detect drug-induced kidney injury in people earlier than is now possible, and help health care professionals better manage potential kidney damage from drugs.”

This advanced use of biomarkers represents a quantum leap in our understanding of molecular toxicities and organ damage - these tests detect cellular damage in a matter of hours rather than the actual kidney dysfunction which had occurred over several days by the time the traditional tests of blood urea nitrogen (BUN) and creatinine have become elevated.

The development of these types of biomarkers was also predictable. Over 10 years ago - with prompting by senior industry scientists - I had several discussions with Congressional and NIH staff about the potential value of government support for validating these types of biomarkers. It was important that the government take the lead in developing these tests since all companies would benefit once the biomarkers were validated, and thus the research was beyond the scope of any single company. This reality led to the formation of the public-private coalition to conduct the research to validate specific biomarkers. However, the formation of this consortium is somewhat remarkable because of the structural/cultural barriers between the industry and the regulatory and scientific agencies, and the extreme public scrutiny and criticism of any collaboration between the pharmaceutical industry and its regulatory agencies – no matter how valuable the public benefits.

The development of the kidney related tests is not an isolated advancement. The non-profit organization managing this initiative is working on similar tests for cardiovascular diseases, cancers, and other diseases. Patients and clinicians certainly hope that similar tests are developed quickly for these conditions, and that they will improve the speed and quality of developing and approving new and better medicines.

Accelerating these advancements will depend on how Congress funds the FDA to increase its scientific capabilities and modernize its information technology, as well as how much attention the next President gives to the FDA’s activities - which he should since they touch every American and affect ~25% of the US economy.

Are people who participate in clinical trials patients or subjects? This may seem like a minor rhetorical difference, but I believe it has tremendous implications for health and biomedical research policy. Let me explain why -

Clinical trials are experiments to discover new knowledge. Their intent is to see if a new way of treating a specific disease or condition is better than, the same as, or worse than, another option – either a placebo or an established treatment. Therefore, when people agree to participate in a clinical trial they are participating in this experiment, and their fundamental goal for participating should be to help future patients by expanding biomedical and/or clinical knowledge. As part of their participation, they may receive some benefit – IF the experimental therapy does prove to be beneficial. Therefore, they are not patients; they are subjects within the clinical trial.

I often see phrases like “clinical trial patients” or “patients in clinical trials,” and I understand what they are talking about, since for many patients with serious conditions that lack good treatment options, clinical trials offer some hope. However, I think that the term muddles the distinction, and can lead to conflicting responsibilities for the clinician-investigators conducting the trials and the patient’s primary physicians. This is one reason that I believe that patients who elect to participate in clinical trials should maintain a relationship with their primary care physician during the clinical trial – even if the researcher in charge of the clinical trial is responsible for all their clinical care. This also means that the clinical investigator and the primary care physicians for the subjects in the clinical trial need to have regular communications - both before and during the person’s participation in the clinical trial.

When the person’s primary care physician is also the clinical investigator in the clinical trial, these lines are easily blurred, and this can lead to problems – something that all clinician-investigators struggle with. This is why clinical trials have protocols that are pre-approved by at least one Institutional Review Board (IRB) that is charged with protecting the rights and welfare of subjects in the clinical trial. (IRBs are also involved with monitoring the clinical trials and modifying the protocols as needed during the course of the trial.)

I was reminded about this issue by an article in the May 1^st issue of American Family Physician that discusses when and how it is OK to use a placebo in clinical practice, i.e. for patients rather than clinical trial subjects. The article lays out a bright line for physicians - “do not lie” - as well as referencing an older article* that lists five conditions that should be met before giving a placebo to a patient:

1. There is a well-established, durable physician-patient relationship
2. There is a concrete diagnosis that does not mandate or support the use of other “active” interventions
3. The patient specifically requests that the physician provide some form of intervention
4. The use of such agents is a consideration of last resort
5. The use of such agents does not substitute for, or interfere with, diagnostic and therapeutic diligence

The distinction here is between using a placebo clinically, and using it in a clinical trial. For someone to become a subject in a clinical trial, they need to first give their informed consent so they are aware of the risks involved with their participation. Having a physician give such informed consent in clinical practice when using a placebo might actually undermine the placebo effect, and thus remove any benefit the patient might receive from the placebo. The AFP article specifically counsels that if a patient asks about a recommended treatment that is a placebo, that an appropriate response from their physicians should be something like - this may not directly affect your condition, “but it may turn on other mechanisms that might be important for your health and make you feel better.”

Any additional thoughts on this issue?

* Bok, S., “The ethics of giving placebos,” Sci. Am. 1974; 231 (5): 17-23

For several years it has been clear that funding limitations are impairing the FDA’s ability to attract and retain qualified clinicians and scientists to review applications for new drugs and biologics, and to support their internal research and analysis concerning new drug development, manufacturing and monitoring technologies – particularly for biologic medicines. In addition, the FDA hasn’t been able to update its information technology systems to maximize staff productivity. (I suspect some people will be tempted to comment on the “productivity” of government employees, but I have found the FDA’s professional staff generally very qualified and hard working.)

On Tuesday, the Energy and Commerce Committee in the US House of Representatives held a hearing about the FDA’s ability to adequately oversee foreign production of medicines being sold in the US. This was part of the ongoing dialogue that was heightened by the contaminated heparin from China.  (The Government Accountability Office also released their study about foreign drug inspections on Tuesday.)

What I found interesting about reports from the hearing was its predictable political theatrical aspects: Chairman Dingell excoriating the FDA Commissioner for not admitting that the FDA needs more resources, and Commissioner von Eschenbach responded that he had asked for more funds to increase foreign inspections. But he also adhered to the Administration’s rhetoric that reforms are needed in addition to some extra funding. As the NY Times reports him saying, “the solution needs to be much more comprehensive than simply inspecting a facility.”

While this hearing focused on foreign inspections – which are clearly a concern – I believe the FDA also needs to step up their monitoring of medicines once they are already here in the US. While counterfeit medicines don’t appear to be a major problem in the US (at least yet), the continuing news reports of problems with generic medicines are worrisome – including a Wall Street Journal report that including the information that one patient’s generic pills had no markings, which is a violation of FDA regulations.

The FDA’s budget, staffing and technology challenges, together with the growing domestic and international quality and safety problems with various medicines raises concerns about how well prepared the FDA is to review and monitor biosimilar medicines and genomic based diagnostics.

I believe that Congressman Dingell is right, and that Commissioner von Eschenbach needs to be a stronger advocate for increased funding for the FDA, even if it means tearing up the Administration’s script he’s told to stick with. This Administration has only another 9 months of shelf life, so he doesn’t need to worry about being fired for speaking off-script – unless he is planning on running for office and wants to remain the good graces of the Republican Party. And if this is the case, then he is violating his duty as FDA Commissioner to fulfill the agency’s mission:

The FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.

I’ll get off my soapbox now, and check to see if the soap that came in it was made in China.

Medical information can change how clinicians treat patients, how patients care for themselves, and how healthcare payers promote or prevent the use of treatments and diagnostic tests. However, this information can act as either a broad sword or a scalpel, and produce good or bad outcomes.

A recent report from a Canadian new service about an article from the Canadian Medical Association Journal describing the outcomes from warning about the use of anti-depressants in children brings this issue down from a general concept to being very specific. This news report stated:

Two years after Health Canada warned about prescribing anti-depressants to children, the number of children and teens who died by suicide increased 25 per cent after years of steady decline, major new Canadian research shows.

And the increased suicide rate coincided with a 10-per-cent decrease in the rate of visits to doctors for the treatment of depression in children.

For the study, researchers tracked what happened in Manitoba before and after Health Canada warned in 2004 that newer antidepressants may be associated with an increased risk of “suicide-related” events in patients under 18.

They found the warning was followed by an overall 14-per-cent drop in antidepressant use among children and adolescents, fewer visits to doctors for depression, and - among eight- to 17-year-olds - increased rates of completed suicide.

More than 90 per cent of the children and teens who killed themselves were not taking antidepressants when they died.

Published Tuesday in the journal of the Canadian Medical Association Journal, the study is the first to document “such a wide range of unintended health consequences” from a major drug warning, the authors say.

Lead author Dr. Laurence Katz, a child and adolescent psychiatrist in Winnipeg, warns the increased risk of suicide could be a “random fluctuation.”

“We can’t say the warning, or the change in antidepressant use or the physician office visits caused changes in suicide rates,” says Katz.

The suicide rate among children and teens was also still relatively small, from 0.04 for every 1,000 children and adolescents before the warning, to 0.15 per 1,000 after.

But Katz worries the widely publicized drug warnings have led to more cases of untreated depression, and an impact “beyond what was intended.” The drop in doctors visits for depression suggests that some vulnerable children are getting no treatment, including psychotherapy, at all. He says his hunch is that families were afraid to go to the doctor for fear their child would be put on medication.

“But that’s not the only treatment for depression. Not going to the doctor deprives you of all forms of treatment.”

If anything, researchers expected office visits to go up after the warning was issued because physicians were urged to increase the monitoring of patients for potential adverse reactions.

Katz, an associate professor of psychiatry at the University of Manitoba, says the drug warnings and media response may have “generated a lot of fear.”

“Understandably parents who kept bringing their children, their teenagers in for troubles with depression were already struggling, and fearful (and) often appropriately cautious about whether their child or teenager should be put on a medication.”

Katz believes the findings could be applied to any Canadian jurisdiction. Other studies coming out of the U.S. are showing similar results. [Emphasis added]

The antidepressant warning involved drugs known as SSRIs, or selective serotonin re-uptake inhibitors, a class that includes Prozac, Paxil and Zoloft, as well as serotonin noradrenaline re-uptake inhibitors (SNRIs), which include Effexor. The drugs have not been approved in Canada for children, but doctors have prescribed them “off-label,” which they are legally permitted to do, to tens of thousands of toddlers, children and teens for depression, social phobia, anxiety and obsessive-compulsive disorders.

In 2003 the U.K. banned antidepressants for children. The only exception was Prozac. Studies have shown the drug is safe and effective in children.

A year later, Health Canada warned that people taking the newer-generation antidepressants may experience behaviour or emotional changes that may put them “at increased risk of self-harm or harm to others.”

Katz says he didn’t have a problem with the warnings themselves. But he says some people leaped to the assumption “that these medications lead people to kill themselves.”

[The report also notes that, “For young adults, there was no significant change in the rate of completed suicide.”]

Obviously, the outcomes found in this study are very worrisome, but it also a too dramatic example of the principle of unintended consequences.

It also reminds me of how a news story in the early 1990s about adverse reactions with the second medicine to treat AIDS.  This news report caused many AIDS patients to stop taking the medicine, and given that there was only one other medicine to treat AIDS, this certainly wasn’t a good thing for their long-term survival

Although correlations don’t prove causations, I think this study definitely underscores the importance of healthcare regulators - and their media colleagues - carefully considering how they present new health information and notices to the public - for both good findings or dire warnings. With all the proposals to empower patients to make their own decisions through consumer directed insurance plan, and to give people more health information, there should also be much more research into how people respond to health related information delivered in different forms from various sources.

I’m usually either supportive or neutral about alternative therapies because they generally aren’t harmful, and can be beneficial. However, there seem to be more and more recalls of these products by the Food and Drug Administration (FDA) for mislabelings that are significant, although seemingly not extremely dangerous.

On the other hand, I was struck by a press release I got yesterday from the FDA about a recall for the dietary supplement products “Total Body Formula” and “Total Body Mega Formula.” The recall was because these products had more than 200 times the amount of selenium than was printed on the products’ label – and the press release noted that, “Excessive intake of selenium is known to cause symptoms to include significant hair loss, muscle cramps, diarrhea, joint pain, fatigue, loss of finger nails and blistering skin.”

I guess this is another instance of how too much of something that is normally good, can be, well, not so good. And with 43 adverse reactions reported to the FDA, the recall seems like a very good thing.

UPDATE: The FDA updated their warning and information on this issue this afternoon - click here to see the FDA website notice.

After writing about Follow-On Biologics in a recent posting, I saw a notice about Health Canada’s proposal for how they would approve biologic products that are similar to already approved biologics whose patents have expired. They call these products Subsequent Entry Biologics (SEBs), and the proposal is open for public comment from March 14, 2008 until April 16, 2008.

While the draft guidance is lengthy, it does strike an overall well-balanced tone:

• “SEBs are not ‘generic biologics’”
• Approval of an SEB does not mean it can automatically be substituted for the original biologic that it is “similar” to
• Comparative studies will be required to generate data showing similarity to the original biologic in terms of quality, safety and efficacy

In many ways, the draft guidance is similar (no pun intended) to the process the US FDA used to approve some generic drugs prior to the 1984 Hatch-Waxman Drug Price Competition and Patent Term Restoration Act. (This was the law that created the abbreviated new drug application (ANDA) process which allowed generic drugs to only demonstrate bioequivalence, and obviated the requirement that they replicate the original drugs safety and efficacy trials.) By referencing published studies about the innovator drug as proof of safety and efficacy, these so called “Paper-NDAs” allowed generic companies to be approved much faster and more cheaply.

Health Canada’s “paper biologic licensing application” like proposal, would allow them to rely on published information about the original biologic, while also handling each SEB application individually to decide what additional studies need to be done to demonstrate quality, safety and efficacy of the SEB.

As I pointed out in my previous post, there are many levels of structural and biological complexity with biologic treatments, so Health Canada’s draft approach seems very appropriate and reasonable.

What do you think?

My last post contained some perspectives about fake medicines. That same day, the LA times ran an article about California’s long-delayed pedigree requirements for tracking prescription medicines. This law was prompted by the discovery of fake medicines for HIV/AIDS in 2000, and was intended to achieve what the FDA has been trying to implement for many years.

The LA Times article blames the delays in the state’s drug tracking system on the industry - from the manufacturer to the retail pharmacy. I suspect that the real challenge is not in the technical or cost aspects from the manufacturers - who certainly have lots to gain by stopping counterfeits of their products from being sold instead of the real thing, but from the wholesalers and to a lesser extent the pharmacies.

I’m assuming that wholesalers don’t knowingly sell counterfeit medicines, but under the current system, they can potentially make a lot of money doing so - particularly when buying them allows for a larger mark-up to the pharmacies than the real medicine. This is part of the economic reality of wholesalers, who in effect are arbitraging the differential costs of pharmaceuticals as a commodity by buying someone else’s excess supply and delivering it where it is needed. Now normally this would be market forces working to efficiently delivery medicines to where they were needed. However, without adequate pedigrees (i.e. paper or electronic documentation demonstrating the entire chain of custody of the medicines from the time it left the manufacturer), there is a great economic incentive for counterfeiters to push their fake medicines into this supply chain and make a huge profit.

Of course, the pedigree system needs to be sophisticated enough that it too can’t be forged - otherwise it is worthless. This is why retail pharmacies may be balking at the cost of implementing a system where they aren’t going to benefit, and don’t believe they are part of the problem. In general, pharmacies, don’t have great incentive for selling fake medicines - they would get paid the same dispensing and product fees whether the product was real of fake. The only case where pharmacies would increase their profits is if they were to be able to buy the fake medicines for less, but this would probably only occur for large chain pharmacies where they are essentially acting as their own wholesalers and wouldn’t be the case for the independent pharmacies - the few that are left.

Because pharmaceutical companies have incentive to track shipments of their medicines and make sure they aren’t stolen, some are starting to use RFID technology. This is surely a big investment that is worth the cost. Implementing a secure pedigree tracking system might be more costly, but would certainly be a worthwhile expense to ensure the safety and quality of medical care.

In general health policy people in the US don’t like to talk about counterfeit medicines because it raises the potential that people won’t trust their medical systems or their medicines. That attitude would be OK if there was nothing to be done about it, but since there is a solution, I think it should be talked about. The other challenge to pushing for drug tracking systems is that as health reform initiatives go, it’s not as “sexy” as electronic medical records, checklists, “evidence based medicine” or eliminating fraud and abuse and using the savings to expand insurance coverage to the uninsured. But it is a doable improvement. The challenge is figuring out how to pay for it, and convincing all the stakeholders effected to work together to make it happen.