Free Telemedicine Mobile Apps and FDA on Social Media

When the “i” series of the Apple products (iPod, iPhone, iPad, iTunes) drastically change the way we access music, videos, movies, games, and friends/families, I naturally think those things will eventually be applied in science and medicine as these two disciplines are global-oriented, data-driven, and information rich–exactly what those devices are designed to handle.  Not surprisingly, the smartphone/tablet world evolves daily with newer chips/designs/features/functions, and a gigantic software application market has constantly attracted huge interests in the music, gaming, entertaining, and healthcare industries.

The Age of Telemedicine – Mobile Apps in The Fingertips
Apps grow like weeds to run on several popular smartphone platforms, such as iPhone, Android, Blackberry, Windows 7 phone, and Symbian.  A blog run by a medical student and a medical resident on mobile medical apps contains a truck load of apps information and countless app screen shots that are eye-catching.  As of 14 Dec 2010, their top 20 free iPhone medical apps are:

1. Medscape (mini-textbook)
2. Micromedex (prescription medical reference)
3. New England Journal of Medicine (must read medical journal)
4. Epocrates (medical reference tools)
5. Calculate (Medical Calculators by QxMD)
6. Radiology 2.0 (case learning radiology tool)
7. Skyscape [RxDrugs: drug reference tool and OCM (outlines of Clinical Medicine): disease pathology information]
8. Living Medical Textbooks (information rich)
9. ReachMD (medical radio)
10. Neuromind (simple reference tool)
11. Prognosis (diagnosis simulation)
12. Harvard’s Public Health News (news)
13. Radiopaedia (radiology teaching files)
14. AHRQ ePSS [public health tool by the US Department of Health and Human Services (HHS)]
15. Dragon Medical Search (search tool)
16. Epocrates calculators (for specialist )
17. MedPage Today (breaking medical news)
18. Doximity (facebook for doctors)
19. Dropbox (help medical workflow)
20. 3D Brain and Lost it (brain anatomy and point-of-care on diet and exercise)

As of 24 Jan 2011, their top 15 free Android medical apps are:

1. Medscape
2. Epocrates
3. Skyscape
4. Evernote (organization tool)
5. Calculate (Medical Calculators by QxMD)
6. MedPage Today
7. Harvard’s Public Health News
8. Monthly Prescribing Reference (MPR) (drug reference)
9. Standard Dictations (basic templates to read while dictating, great for interns)
10. AHRQ ePSS (electronic preventive services selector)
11. PubMed Mobile (medical reference)
12. Ob Wheel (pregnancy management)
13. Eponyms (reference material)
14. Speed Anatomy (anatomy reference)
15. Calorie Counter (diet and exercise application)

In addition, the US Department of Veterans Affairs comes out with a FREE PTSD (Post-tramatic stress disorder) Coach app to help learn and manage symptoms that commonly arise after drama.  Want to see more? Apple’s App Store has more and yet again more at Amazon.com appstore for Android.  If you want to gain more information on new development of mobile medicine application, the “Telemedicine and e-Health” journal is a good place to start.

FDA’s Media Channels and Approved Apps

Everyday, we are inundated by information tsunami elicited by technology innovation earthquakes–novel gadgets, new apps, extensive cloud computing/storage, you name it.  Numerous organizations jump on social and interactive media bandwagon to engage with interested parties, no exception for FDA, evident by a list of tools to gain access to the FDA information.   However, the FDA has not yet revealed its social media guidance on promotion of products and services.

The mobile apps have entered into a serious development to function as a medical device-equivalent.  The first iPhone and iPad mobile application approved by the FDA with 510(k) clearance is called Mobile MIM by MIM Software.  Medical doctors can view images and make medical diagnoses based on computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine technology, such as positron emission tomography (PET). However, regular workstations should be used if available.

Until next post, keep on reading and writing!!

Off-label Use vs Off-label Marketing

Off-label Use and Off-label Marketing Are Different

Off-label use and off-label marketing, on the surface, sound similar but they are two distinct practices in the pharmaceutical industry and medical community.  Off-label use is a practice by which physicians prescribe an F.D.A-approved drug for an unapproved indication/dose/age/administration.  Sounds strange but off-label use has been widely and legally implemented in the medical community for a long period of time.  Off-label marketing, on the other hand, is a practice by a drug company to promote drug use in unapproved indications.  In other words, physicians are legally allowed to prescribe drugs for any purpose (based on their professional assessments), but companies are not allowed to promote drugs for unapproved uses by the F.D.A.

Off-label Use Example

An increasing number of antipsychotic drugs have been brought to market in recent years.  The earlier version of the antipsychotic drugs (aka typical or first generation antipsychotics) are mainly to treat schizophrenia, bipolar disorder, and delusional disorder.  Nowadays, more and more non-psychotic symptoms, like depression, anxiety, autism, obsessive compulsive, just to name a few, are treated more prevalently with newer version of antipsychotic drugs (aka atypical or second generation antipsychotics).  A recent research by groups at the Stanford University and University of Chicago showed that atypical antipsychotic drugs are prescribed frequently for non-FDA approved use that lack strong evidence to actually benefit patients.  This widespread post-market off-label use of the FDA-approved second generation antipsychotics needs to be monitored more closely should unknown side effects outweigh the benefits.  Aside from unproven benefits of off-label use, medicare and private insurance companies often deny coverage for off-label prescription.

Off-label Marketing Example

In September 2010, Novartis has agreed to pay a hefty $422.5 million fine for off-label marketing over six drugs (Trileptal, Diovan, Exforge, Sandostatin, Tekturna and Zelnorm).  One of the off-label marketing practices (blood-pressure drug Diovan) was revealed and kind of shocking as this marketing gimmick went too far that highlighted the unethical medical practices due to greed.

In recent months, Pfizer has been ordered to pay a $142.1 million fine for violating federal racketeering laws in the marketing of Neurontin (gabapentin), an anticonvulsant drug approved by the F.D.A. in 1993 for epilepsy indication.  Neurontin was marketed to be effective in treating bipolar disorder and migraines and was hidden for suicide risk.

On 28 February 2011, Elan Pharmaceuticals pleaded guilty of violating the Food Drug and Cosmetic Act for off-label marketing on its epilepsy drug Zonegran approved by the F.D.A. in April 2000.  Again, a hefty criminal fine of $97 million was paid.

Along the same line, several companies had faced serious legal and financial consequences from off-label marketing.  In the past few years, a handful of pharmaceutical companies had settled with federal government on their health care fraud, and here they are:

  • Pfizer: $2.3 billion
  • Eli Lilly: $1.4 billion
  • Allergan: $600 million
  • AstraZeneca: $520 million
  • Bristol-Myers Squibb: $515 million
  • Forest Laboratories: $313 million

Some Thoughts

One psychiatrist once told me that she has stopped using free pens given by drug companies as she later noticed that she wrote more prescriptions from the drug companies that brilliantly use their freebies to subconsciously influence a physician’s professional judgment.  How can a patient assure that a physician is not materialized in any way making prescription recommendation?  Is the drug prescribed based on the best interest/benefit for patient or off-label use for empirical reason or off-label marketing for kickback?  That said, with internet available at your fingertip, it is worth self-educating and doing due diligence on one’s prescribed drug.

Until next post, keep on reading and writing!!

Medical Device Regulation Dilemma

Spotlight on Medical Device Regulation Policies

On 7 February, President Obama gave a speech to the Chamber of Commerce during which he addressed some issues regarding regulations, such as:

We’re improving the way FDA evaluates things like medical devices, to get innovative and life-saving treatments to market faster.

According to the FDA’s device regulation and guidance, medical devices are classified into Class I, II, and III.  Most Class I devices do not require notification.  Most Class II devices require premarket notification 510(k) and most Class III devices must have both 510(k) clearance and receive premarket approval.  In other words, the higher the class, the more stringent the regulatory requirement.  Recent news about medical devices is centered on 510(k).  So what is 510(k)?  From FDA’s website:

The 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device that is not subject to premarket approval (PMA).

Medical Device Review Standard Challenged

Recently, the FDA has reviewed its 510(k) approval actions, aiming to streamline and shortening review processes.  But there were alarming signs that past review processes already existed flaws that could potentially challenge the FDA’s attempt to simplify medical device review processes. For instance, the New York Times reported that in the past five year there were over 68 recalls and more than 22,000 reports of malfunctioning external defibrillator devices.  This prompted the FDA’s advisory panel to request tighter oversights.  A study also found that about 70% of the recalled devices received FDA abbreviated agency protocol review, which again alerts current regulatory processes.  Despite these seemly increasing numbers of recalls and defective devices, medical device makers complained that the FDA’s stricter and prolonged regulatory scrutiny had already forced them to move operations to overseas, like China, Brazil, India, and Europe.  Again FDA is sandwitched between medical device makers who prefer simpler approval processes and consumers who demand stricter standards and safer devices.  A tough role.

Greenlights on Recent Medical Devices

From my Google Alert notice, at least four companies received greenlight on their 510(k) clearance and approval, here they are (and hope more to come):

1. Diazyme’s 25-Hydroxy Vitamin D Assay (January 24, 2011)

2. Pacific Consolidated Industries’s On-Site Oxygen Generators (February 7, 2011)

3. Depuy Orthopaedics’s New Titanium Foam Implants and revision hip system (February 15, 2011)

4. Allergan’s Lap-Band Device (February 16, 2011)

Until next post, keep on reading and writing!!

Eyes on Follow-On Biologics

Drug Approvals Sliding and Patent Cliff Approaching

Drug development is a painfully slow, costly, and risky business.  It’s a hit or miss and the odds can be a multi-billion dollar question.  In 2010, the FDA approved 21 new drugs (new molecular entity and biologics), slightly down from 25 drugs in 2009.
These 21 drugs from the FDA database (NDA Chem Type 1 and BLA) are:

Company Brand Name Active Ingredients
ACORDA AMPYRA DALFAMPRIDINE
NOVO NORDISK INC VICTOZA LIRAGLUTIDE RECOMBINANT
GENENTECH ACTEMRA TOCILIZUMAB
SHIRE HUMAN GENETIC VPRIV VELAGLUCERASE ALFA
AUXILIUM PHARMS XIAFLEX COLLAGENASE CLOSTRIDIUM HISTOLYTICUM
CHEMISCH FBRK KRSSLR ASCLERA POLIDOCANOL
ORPHAN EUROPE CARBAGLU CARGLUMIC ACID
BAYER HLTHCARE NATAZIA DIENOGEST; ESTRADIOL VALERATE
GENZYME LUMIZYME ALGLUCOSIDASE ALFA
AMGEN PROLIA, XGEVA DENOSUMAB
SANOFI AVENTIS US JEVTANA KIT CABAZITAXEL
VISTAKON PHARMS LLC LASTACAFT ALCAFTADINE
MERZ PHARMS Xeomin incobotulinumtoxinA
LAB HRA PHARMA ELLA ULIPRISTAL ACETATE
NOVARTIS GILENYA FINGOLIMOD
SAVIENT PHARMS KRYSTEXXA PEGLOTICASE
BOEHRINGER INGELHEIM PRADAXA DABIGATRAN ETEXILATE MESYLATE
CEREXA TEFLARO CEFTAROLINE FOSAMIL
SUNOVION LATUDA LURASIDONE HYDROCHLORIDE
THERATECHNOLOGIES EGRIFTA TESAMORELIN ACETATE
EISAI INC HALAVEN ERIBULIN MESYLATE

I can imagine even just “one” more drug being added to the list can mean huge revenue to a company, hope to patients, and rewards for collective efforts from hundreds, if not thousands, of people involved during the drug development and evaluation processes.  So the declining drug approval number (from 25 to 21) is a warning sign to the industry.  To make matter worse, Nature news reported that looking forward, drug companies will encounter the most fierce competition from the generic drug makers in 2011 and 2012 because many blockbuster brand name drugs will face patent expiration.  Together, thinning drug pipelines, patent cliffs, and stricter regulatory policies all put heavy pressure on drug companies.  How will the drug companies react?

Biosimilars = Follow-On Biologics = Me Too Drugs

When the patent of a brand-name drug from the pharmaceutical/biotech company XYZ expired, other companies are allowed to copy the formula to make the same drug, called generics, to sell for a lot less and then to compete with THAT brand-name drug.  Imagine a secret recipe is published from a world-renowned chef in a three star Michelin restaurant, so now you and I and everyone can follow the instruction to make the same food, well, in theory.  In order to not lose much revenue after patent expiration, many drug companies have gradually stepped into generics market and have gone to lawmakers for help.  Recently, Merck & Co shook hands with contract researcher Parexel International Corp to develop biosimilars.  Biogen Idec Inc. also plans to expand into biosimilars as they will provide meaningful revenue streamSimilar interests from several big pharmaceutical companies were also expressed in the January’s JP Morgan healthcare conference in San Francisco.  It seems there will be a stronger competition in the years to come.

Until next post, keep on reading and writing!

Stem Cell Clinical Trials Get Going

A Brief Primer on Stem Cells

If you were to ask biologists what a stem cell is, chances are you will get several definitions with slight variations.  By and large, self-renewal (i.e. reproduce itself) and capacity of differentiation (i.e. produce different types of cells) are the two common denominators of a stem cell definition.  The National Institutes of Health hosts a stem cell resource website that contains easy-to-understand scientific information as well as political, ethical, and healthcare discussions about stem cell research and implications.  Despite the political headwind on Obama Administration’s stem cell policy, the burgeoning stem cell research activities, interests, and potentials cannot be ignored.

Five Stem Cell Clinical Trials Got Go-Ahead

The first FDA-approved stem cell trial using human embryonic stem cell (hESC) to treat spinal cord injury was given to Geron (Menlo Park, CA) in January 2009.  However, Geron’s preclinical animal study showed small cysts developed within the injection site, which prompted a hold in human clinical trial for further investigation.  Fast forward to July 2010, the FDA lifted the hold and gave the first stem cell clinical trial OK to Geron to treat spinal cord injury.  In October 2010, Geron began its first stem cell therapy in a human patient.

Advanced Cell Technology’s retinal pigment epithelium therapeutic cells received the FDA’s clearance in November 2010 and January 2011 for initiating Phase I/II clinical trials on two eye-related diseases, juvenile Stargardt’s Macular Dystrophy and dry age-related macular degeneration.  These two eye diseases affected ~30 million people in the US and Europe and may ultimately lead to blindness.

Aldagen, a biopharmaceutical company developing adult stem cell products on tissue repair and regeneration, received a green light from FDA in January 2011 to start Phase II clinical trials to test stem-cell therapy for stroke.  Finally, Pluristem therapeutics wins FDA-EMEA (European Medicines Agency) joined approval for stem cell trials in which the company will conduct a Phase II/III study of its product on blocked arteries, and a Phase II study on ischemia colitis (i.e. inflammation in the large intestine due to loss of blood flow).

Will Stem Cell Therapy Live Up to Expectation?

Gene therapy, once held a high hope in the 1990s, became a stymie in clinical implication after a patient died from multiple organ failures following a gene therapy trial in 1999.  One of the biggest challenges in gene therapy is unwanted immune responses elicited by gene therapy carries, mostly viruses.  As of this post is written, FDA has not yet approved any human gene therapy product for sale.  A 2006 Nobel prize winning discovery, RNA interference, has become a new therapeutic intervention candidate tested by many biotech/pharmaceutical companies.  Several RNAi-based clinical trials are in progress.  Recently, Roche announced to terminate RNAi research and development, sending uncertain signals to companies developing RNAi-based therapeutic agents.  The next wave of therapeutic intervention is no surprise landing on stem cell.  With private and public funding supports, adult human stem cells and induced pluripotent stem cells have been discovered and are under intense studies in the hope to replace human embryonic stem cells, mainly due to ethical issues.  Despite numerous challenges ahead to bring stem cell therapy into clinical implications, I remain optimistic to this new technology, but only time will tell.

Interesting Reports on Potential Application of Stem Cell

More on stem cell news and reports:

Until next post, keep on reading and writing!!

Avastin Hits the Breast Cancer Indication Wall

A Brief History of Avastin

Avastin (its generic name: bevacizumab) was developed by the biotechnology giant–Genentech (bought by Roche in March 2009), and was first approved by the U.S. FDA in 2004.  Avastin is a biologic antibody targeting “vascular endothelial growth factor” that involves in blood vessel formation.  By disturbing the blood vessel formation (a.k.a. angiogenesis) in tumors, the tumor cells lose nutrition and oxygen supplies and therefore die.  Avastin, in combination with intravenous 5-fluorouracil-based chemotherapy, has been used in treatment of several solid tumors, like metastatic colorectal cancer, metastatic kidney cancer, and non-small cell lung cancer.  In addition, in combination with paclitaxel (another chemotherapy drug), Avastin was used in treatment of metastatic HER2-negative breast cancer patients.  Unfortunately, the new clinical data from US trials showed that Avastin is not effective.  Based on the new scientific data, the FDA recently had decided to recommend removal of breast cancer indication from Avastin label.

Contrary Results of Avastin in Breast Cancer Treatment

Initially, I was grieved by Avastin’s failure of showing benefits in disease-related symptoms or survival to breast cancer patients.  But turn on my glass is half-full thought, at least Avastin is still valid in other treatment indications.  However, Genetech, the company marketing the drug doesn’t think so because the European Medicines Agency gave a green light to Avastin, arguing against FDA’s recommendation of Avastin removal from breast cancer indication.  Genentech will request a hearing with FDA by 18 January 2011.

Some Sticky Issues in FDA’s Decision on Avastin

In 2008, Avastin was granted “accelerated approval” for metastatic breast cancer treatment in combination with paclitaxel (called E2100 study).  Few years later, more science-based evidence from two clinical trial studies (named AVADO and RIBBON1) showed that Avastin did not benefit breast cancer patients.  Some patients claimed Avastin is helpful and are afraid the FDA’s decision will affect Medicare reimbursement because the annual spending of Avastin can reach $88,000, not many patients can afford such expensive treatment if Medicare doesn’t pay for it (or part of it).  You can read more on:

Until next post, keep on reading and writing!!  Happy New Year 🙂

The FDA Takes on the Food Safety Policing Role (Soon?)

Sick from Food? Not Rare Anymore

People from the place I grew up used to joke about the food that sold by street vendors: not clean enough but won’t get you sick.  Most of the time, the food materials were produced locally and prepared right in front of you; if you don’t feel comfortable about the sanitary condition of the food preparation process, you just don’t buy it.  If you do get sick, though it was not that common, come back to complain and ask for improvement or compensation.  Most food vendors operate on the ethical and moral basis–make food for the customers the way they make their own food.  Good reputation will serve their small businesses well by word-of-mouth.  Now, time has changed.  With the industrialization of food production and distribution, food-borne illnesses have increased in the numbers of outbreak and on a bigger and broader scale.  Recent Salmonella contaminated eggs causing nearly 2000 illnesses is just the tip of the iceberg.

Something about Legislation You Need to Know

On 30 November, the US Senate passed a law on food safety that renders the U.S. Food and Drug Administration (FDA) a bigger muscle to stop unsafe food reaching to consumers.  Although the food safety bill was passed by the US Senate, it may or may not eventually become a law.  According to Nature News, the food safety bill will require further negotiation between the Republicans and Democrats.  Go figure!

The bill could conceivably be defined to raise taxes, by imposing fees on food importers and on domestic manufacturers whose food is subject to a recall when it is discovered to be tainted. If those fees are defined as taxes, then, under the US Constitution, the bill must first be passed by the House of Representatives. The House passed a food safety bill in July, 2009, but it is different than the Senate version — meaning that, for the Senate bill that was passed on Tuesday to become law, it must first be voted on by the House, and then again passed by the Senate, before being signed into law by the president.

Beyond the FDA’s Policing Power on Food Safety

Have you ever seen a car running red light or speeding but no police around to catch it?  Have you ever wondered the traffic lights, signals, and signs are good enough to keep cars and pedestrians safe?  The traffic safety enforcement is only as useful as the people who actually obey it.  Likewise, I think the FDA’s new food safety regulatory power will only be effective when all parties, including farmers (produce, meat, egg, milk, etc.), food production and process companies, food inspectors, importers/exporters, and consumers, agree to cooperate to achieve the same goal–food safety to all humans and animals alike.

Food Safety Issues Appearing in the Media

A while ago, one of my co-workers lent me a book called “In Defense of Food: An Eater’s Manifesto” by Michael Pollan.  My eyes were wide-opened by several examples of how our nutrition was compromised by industrialized food process.  In conjunction with recent food safety legislation, I also recommend several media reports about food safety and regulations:

Until next post, keep on reading and writing!!