In Absentia

Tags

cancer, digital media, integrated medicine, integrative oncology, Just Oncology, oncology, richard just md, social media

By Gregg A. Masters, MPH

When I first approached Dr. Just on his potential interest in the emergence of social media in healthcare in general and medicine in particular, we engaged in conversations that generally tethered to a contribution to a ‘legacy’ theme.

Reflecting on a now 40 year career in community based medical oncology he was thinking about winding down his participation in a full time practice while passing on the deep wisdom and insights developed over the decades.

Considering the explosion of digital media platforms and capabilities, and the low hurdle rate to participate via this medium this consideration was rather timely.

The first order of business was to brand that voice and craft a social media ‘presence’.

As I reflected on his last name ‘Just’, and saw a double entendre opportunity to conflate ‘just’ with ‘oncology’ – I thought how perfect! Lets brand you as ‘JustOncology.com’. Since in this context ‘just‘ could mean ‘Dr Just’, or solely focused on oncology, or even just in the sense of ‘equity’ or fairness in oncology care. In all cases, the branding expression and focus was clean and consistent with his interest to write, speak and counsel others on the journey.

So we created the blog JustOncology and twitter handle @JustOncology (though he principally tweets via @chemosabe1) and shortly thereafter launched the radio show ‘this week in oncology’.

As noted in the masthead above Dr. Just writings would reflect on ‘health, illness & evidence based medicine’. An intentionally broad brush tapestry that included everything from his personal health encounter with heart surgery, the move into value based pricing for oncology services, oncology ACOs, seemingly interminable encounters with EHRs that actually work for the practice, practice mergers, partner relations and the most recent shift into ‘integrative oncology’ which has literally taken him offline for almost a year – at least as a principal contributor to this blog.

So as his partner, de-facto editor and co-contributor, let this post call attention to two projects that fit squarely into the ‘legacy’ theme and Dr. Just’s valuation of and advocacy for truly ‘patient centered care’.

Meet @TumorBoard aka TumorBoard (dot) com and CancerCenter (dot) TV – both projects in the incubator of ideas in search of funding support.

A little history on @TumorBoard includes the following introduction from our concept paper.

Context

A centerpiece of the American College of Surgeons’ Commission on Cancer (COC) standards to accredit hospital based cancer programs is a multidisciplinary conference (aka ‘tumor board’) of doctors and other cancer specialists, who meet on a regular basis to collaborate in the diagnosis and recommend treatment options for cancer patients. An active and vibrant tumor board is an essential consideration in the accreditation process. For further context see the Commission on Cancer’s ‘Cancer Program Standards 2012, Version 1.1: Ensuring Patient-Centered Care.’

As defined by the National Cancer Institute (NCI), a ‘tumor board’ is:

A treatment planning approach in which a number of doctors who are experts in different specialties (disciplines) review and discuss the medical condition and treatment options of a patient. In cancer treatment, a tumor board review may include that of a medical oncologist (who provides cancer treatment with drugs), a surgical oncologist (who provides cancer treatment with surgery), and a radiation oncologist (who provides cancer treatment with radiation). Also called multidisciplinary opinion.

Once a popular collegial if not ‘social’ venue to network and learn from one’s peers, periodically present or consult on cases, possibly earn CME credit, if not grab an occasional meal, tumor board has unfortunately lost some of its attraction and ‘gravitas’.

Increased practice complexity, misaligned financial incentives, declining reimbursement and growing demands on physician time, are some of the obstacles resulting in declining physician participation in traditional hospital based tumor boards. Yet few other comparable multidisciplinary, peer based clinical forums outside of mature integrated delivery systems or academic medical centers have the potential to enable the integrated practice of collaborative, coordinated and evidence based community cancer care.

Realizing the Promise of Multidisciplinary Cancer Care

Many assume multidisciplinary care is better care, since it engages multiple minds in the care process, yet in ‘The Need for Assessment and Reassessment of the Hospital Cancer Conference‘, in the Annals of Surgical Oncology, October 2009, Frederick L. Greene, MD, identifies the traditional weakness of many hospital based tumor boards:

most of these [tumor board] conferences…are based on a “show and tell” mentality rather than serving as treatment-planning conferences utilizing the expertise of the participating multidisciplinary experts….

In other words, traditional hospital based tumor boards have not yet fulfilled the promise of better care or improved outcomes as a result of the assumed value add of multidisciplinary engagement in cancer diagnosis and treatment. Apparently, business as usual ‘silo-ed’ medicine remains embedded in the care process even in the midst of what appears to be multidisciplinary consideration.

Why @TumorBoard?

@TumorBoard intends to uniquely address the convergence of several macro trends:

• The high cost of cancer treatment and parallel shift of a greater share of the total cost burden on to a resource constrained and often health literacy challenged patient.
• A heightened awareness of the need for increased clinical integration and care coordination across an otherwise silo-ed and discontinuous portfolio of specialties.
• Formal recognition that the upside of the multi-disciplinary engagement of cancer specialists (i.e., tumor board), has neither realized nor fulfilled its collaborative promise (see: Tumor Boards (Team Huddles) Aren’t Enough to Reach the Goal).
• Emergence of an informed and engaged ‘e-patient’ (witness the launch of SmartPatients).
• A nascent yet growing pool of technology savvy, patient-centric cancer specialists who value peer based collaborative multidisciplinary care with active engagement of the patients under their care (See e-patients and the Society for Participatory Medicine).

For more information, download the TumorBoard concept paper via tumorboard_description_v1.5.

 

 

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Get to Know ‘Chemotopia’

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cancer, chemotherapy, chemotopia, evidence based medicine, integrative oncology, Just Oncology, medical education, oncology, social media, startUp health, twitter

By Gregg A. Masters, MPH

On the Wednesday, November 7th 2012 broadcast of
‘This Week in Oncology‘ we chatted with medical oncologist, integrative cancer care specialist, and ‘serial entrepreneur’ Steven Eisenberg, D.O., co-founder of StartUp Health Academy’s transformer entry ‘chemotopia‘aka @chemotopia on Twitter.

Disclosure: Dr. Eisenberg is a partner with Dr. Just in Cancer Care Associates for Research and Education (CCARE).

We spoke with Dr. Eisenberg about his most recent entrepreneurial interest known as ‘chemotopia’, where the tagline is:

getting through chemotherapy, together

To listen to the broadcast, click on the show logo below:

The Shell Answer Man

Tags

cancer, clinical trials, clinicaltrials, CME, digital media, evidence based medicine, health, Just Oncology, oncology, participatory medicine, social media, twitter

By Richard Just, MD

Over the past 37 years in practice, I’ve received thousands of requests from patients, family and friends to interpret results of clinical trials.  These requests have increased dramatically with the advent of the Internet.   Many of these reports involve poor trial design or are inappropriate for the patient under consideration.  Sometimes I’ve mumbled to myself “I feel like the Shell Answer Man”.  For those too young to remember, I’m referring to a Shell Oil Co. ad beginning in the 1960’s in which the ‘Shell Answer Man”, replete in his Shell gas station uniform, answered common questions about driving and the uses of gas and oil. He just memorized a script; sometimes I wish I had one.   

Over Labor Day weekend, while in Chicago for a family event, we turned on TV to catch up on the day’s news. As fate would have it, we stumbled upon a healthcare segment on the NBC affiliate.  The reporter was listing items individuals should consider in evaluating results of clinical trials.  It seemed to me that knowledge of these items would be very helpful to people who are not healthcare professionals; people who need some way to filter trials worth pursuing with their physicians.  The following are those questions:

1. Are the patients in the trial separated into groups, with one receiving the drug or regimen being tested (“Experimental Group”) while the other is treated with the agent(s) considered standard treatment (“Controls”)?  These groups are many times labeled “arms.”  The Control Arm may be a placebo if there is no known standard treatment.  This does not mean the patient receives no treatment at all.  These types of studies are considered the “gold standard” of clinical trials in that they involve large numbers of patients who are followed for long periods of time.  This increases the likelihood that resultant findings are valid.  The downside is they take a long time to complete and are very expensive (about $1 billion from start to finish).
2. What is the total number of patients entered into the trial?  As alluded to above, the more the better.  If one study includes 50 patients while another 350 (all other factors being equal), place more trust in the larger trial.
3. What is the length of the study? In other words, how long are the patients followed? Again, the longer the better.
4. Were the patients included in the trial representative of the proposed population to be studied?  For example, if the population to be studied involves pediatric patients, someone over 18 years of age should not be entered into the trial.
5. Who is funding the study? Pay attention here. If the study is paid for by the company who developed the experimental agent, how likely are they to give a completely unbiased report? Of course we want to assume that they will, but unfortunately, some won’t.  A government supported trial is more likely to report balanced findings than an industry funded one. The reporter added that patients should note what the authors say about their study, i.e., do they make overly optimistic claims for their treatments?  Most investigators add some type of cautionary note, like “the proposed treatment looks promising pending further studies.”  This disclaimer recognizes that no study is perfect.  In fact, there has been a marked increase in the number of studies initially reporting positive results that were retracted when similarly designed trials were subsequently negative.  The end result has been a delay in patients receiving appropriate treatments and a horrible waste of money.
6. I’m adding this one on my own. I’ve noticed that one of the most common mistakes people make is to search for clinical trials involving the wrong cancer, not realizing that we identify cancers by their organ-of-origin, not the organ where they spread (metastasize).  An example would be to collect articles about liver cancer instead of colon cancer that metastasized to liver.

As chairman of our hospital’s Investigational Review Committee, I and our members are in charge of reviewing proposed clinical trials conducted in our hospital district.  The above factors, as well as many others, are considered before studies are approved, denied or amendments recommended.  Consideration of the items discussed above could save everyone a lot of wasted time, and even lead to the retirement of the Shell Answer Man.

Drug Shortages: A View From The Trenches

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cancer, clinical trials, clinicaltrials, CME, digital media, Dr Just, drug shortgages, elder wisdom, epatients, FDA, health, health 2.0, innovation, Just Oncology, kris ghosh md, medical education, medicine, oncology, Pacific Oncology, participatory medicine, pharma, physician, research, San Diego, social media, twitter, wellness

A few weeks ago, I had a discussion with Kris Ghosh, MD one of our local GYN Oncologists, (listen here).  We talked specifically about Doxil, the usual second line treatment for recurrent ovarian cancer.  We agreed that the lack of availability of the drug does limit options for these patients, with further increase in already heightened anxiety levels for patients and families.  Add to the mix the increase in stress levels of oncologists and our staffs trying to handle one more insult to a broken healthcare system.  In one patient who was due to start treatment I was able to substitute topotecan (Hycamptin).  Fortunately, she is responding and tolerating the agent very well. We had put her name on our list of patients who were waiting for Doxil when it became available.  So I was able to use the drug allocated to her for another patient with multiple myeloma. The only agent that had controlled his disease was Doxil. I guess the problem worked out well in these cases, but it appears that this shell game is going to become routine.  The question arises:  “Is this the harbinger of rationing cancer care?”

In my residency training in the late ‘60’s/early ‘70’s, I rotated through the Nephrology service when hemodialysis was relatively new.  Just like today, demand for the procedure far outstripped supply.  One of the factors taken into consideration in a negative way was anyone whose renal failure was due to diabetes.  That’s a lot of people!!  Obviously, we were very uncomfortable being put in that predicament.  Hindsight personalized this for me since my maternal grandfather died of sepsis after amputation of one of his legs for diabetic gangrene, my father died of every complication of diabetes and was hemodialyzed for 2 ½ years before his death, and I have type I diabetes and am on an insulin pump but fortunately no signs of renal impairment, yet.  I’m sure my father would never have been treated during my training years.  I’m sure our cancer patients experience similar anxiety and fear when faced our current dilemma.

Causes of shortages are multifactorial.  In Doxil’s case, the manufacturing plant in Alabama was struck by lightning during the tornado earlier this year.  Hard to believe but that’s the story.  Obviously an unpredictable Serious Adverse Event (SAE).  However, most of the chemotherapy drugs in short supply are older agents, e.g., bleomycin, cisplatin, cytarabine, daunorubicin, doxorubicin, etoposide, leucovorin/levoleucovorin, mechlorethamine, thiotepa, and vincristine.  Many are now off patent and therefore priced lower as generics; so not as profitable.  In some cases manufacturing of the drug was stopped in anticipation of newer and, of course, more expensive replacements.  One of the predictable side effects replacing old, cheaper drugs with newer, more expensive agents is pushback from payors who deny coverage/payment.  We then get on the authorization-denial-authorization-denial merry go round many times leading to a teleconference with the medical director of the health plan.  All this takes time and can delay treatment for quite a while, adversely effecting results.  Especially when used with curative intent and when there are no good substitutes, this is unacceptable.  Another complication is the emergence of a “gray market” where drugs from questionable sources pass through unknown hands to our offices at up to 10 times the usual price.  In the ‘90’s we called this brown-bagging.  Trying to keep inventory straight as to which drug from what source belonged to whom was an added challenge.

From the above, it is obvious that health care is big business.  An invaluable source of health care information is, therefore, the Wall Street Journal.  In last weekend’s edition I learned that “Roche Holding AG has stopped delivering its drugs for cancer and other diseases to some state-funded hospitals in Greece that haven’t paid their bills.”  This policy may extend to Spain, Portugal and Italy.  Patients had to purchase chemotherapy from private pharmacies and bring them back to hospitals for administration.  In the US, we find ourselves in a similar situation in that we can’t afford to purchase some drugs for our patients.  So drug shortages are a global issue involving different causes requiring different approaches directed to specific problems.

I found two articles helpful in defining the problem and proposing possible solutions:

1. Link, M., et. al.:  Drug Shortages Threaten Patient Health and Safety; HemOnc today, vol 12 no 15, August 10, 2011, pg 1, 10-12.
2. Johnson, P.E.:  Drug Shortages:  Impact and Strategies; JNCCN, vol 9 no 8, August, 2011, pp 815-819.

Doctors, Patients & Social Media

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community, digital media, doctors, elder wisdom, health, innovation, Just Oncology, medical education, medicine, oncology, participatory medicine, patients, physicians, San Diego, social media, twitter, wellness

A recent report released by QuantiaMD aka @QuantiaMD and the CareContinuum Alliance (CCA) aka @CareContinuum is worth note. The survey was conducted by Frost & Sullivan in collaboration with QuantiaMD  and the Institute for Health Technology Transformation.

‘Social media’ was defined to include: “not only social networking sites like Facebook and LinkedIn, but also professional and patient networking communities specific to the medical field, blogs and sites such as YouTube”).

Executive Summary

Physicians are highly engaged with online networks and social media. Nearly 90% of physicians use at least one site for personal use, and over 65% for professional purposes. Overall, clinicians express significant interest in the potential applications of social media to their professions – whether via online physician communities, online patient communities or sites that could facilitate physician-patient interactions. A group of “Connected Clinicians” is using multiple social media sites for both personal and professional uses. These clinicians are the front-runners in applying social media to medicine, and are most eager to use it to positively impact patient care. Key take-aways from our study include:

• The vast majority of physicians are already using social media; Facebook tops the list for personal use, while online physician communities are driving professional use.

• Physicians familiar with online patient communities believe they positively impact patient health; however, awareness of these sites is low.

• Some 28% of physicians already use professional physician communities, with the highest enthusiasm around using them to learn from experts and peers.

• Clinicians see the potential in online interactions with patients to improve access to and quality of care, but concerns around patient privacy, liability and their compensation for such activities must be addressed.

• There is significant need for secure, convenient forms of electronic communication that clinicians can use to communicate with each other, and with patients.

• Over 20% of clinicians use 2 or more sites each for personal and professional use; these “Connected Clinicians” are the most eager to use social media to improve health care.

• There are opportunities for constituents across the health care system to use social media as a tool for improving patient care.

Our study included 4,033 clinicians and was conducted in August of 2011 on QuantiaMD. QuantiaMD is the leading mobile and online community serving over 125,000 physicians with opportunities to learn from, and exchange insights with, their peers and experts in their fields.

To read the full report, click here.

A big ‘h/t’ to both QuantiaMD & CCA!

Surprise!!!

Tags

clinical trials, clinicaltrials, CME, Dr Just, elder wisdom, Just Oncology, legacy, medical education, medicine, mentoring, oncology, Pacific Oncology, participatory medicine, pharma, physician, podcasting, research, San Diego, social media, wellness

As I was browsing through the Harvard Business Review the other day (seriously, this is not my usual reading material), I happened on an interesting article.  Actually, the piece was an interview in the “Idea Watch” section entitled:  “Defend Your Research; The Color Pink Is Bad for Fighting Breast Cancer”, HBR, pp. 30-31, July-August, 2011.  Professor Stefano Puntoni, an associate professor of marketing management at the Rotterdam School of Management, Erasmus University, was asked to explain the counter-intuitive findings of his research.  He stated:  “Our original prediction was boring.  My research partners-Steven Sweldens of Insead and Nader Tavassoli of London Business School-and I thought pink and other gender cues would make campaigns against women’s diseases, such as breast and ovarian cancer, more effective.  But we found the opposite”.

Perplexed, they delayed publishing their results and kept running tests.  After 3 years, the same basic finding was validated 10 times.  Initially, women who wrote an essay about gender were less likely to donate to ovarian cancer research than women writing gender-neutral essays (42% vs. 77%).  Then, breast cancer banner ads were placed on a website but not mentioned to the women viewing them.  When the site was feminine-oriented, 33% recalled the ads; when gender-neutral, 65% remembered.  The color pink turns out to be one of many feminine gender-cues, but prior to the 20^th century it was actually associated with the male gender.

Most importantly, “these findings seem to fly in the face of the marketing principle that you should build a strong brand that emotionally connects with consumers”.  So why is this?   Interestingly, ideas or concepts that are regarded as threatening or difficult to comprehend elicit defensive responses, mainly denial.  The color pink tends to connect women with the thought that they could die of breast cancer.  Another fascinating fact is that not all gender-cues result in defensive responses.  Mascara ads were placed on control websites and 76% of the gender-primed group recalled these non-threatening ads, even more than the control group (65%).  Additionally, gender-cues involving prostate cancer are not as threatening in men.  The author postulates that prostate cancer is more a disease of older men and has a longer natural history, i.e., it is not associated with impending fatality.

Finally, since pink is synonymous with breast cancer, “is there any way to preserve it but overcome the negative effect”?  Women found pink ads about breast cancer harder to read than more gender-neutral peach ads.  But, men found pink ads slightly easier to read.  One suggestion that results from this is “that seeing more men wearing pink as part of breast cancer awareness may start to break down the color’s effect as a gender cue”.  Another thought is that pink may empower men to donate more.  Obviously,  work in this field is very preliminary.

As a result of the above article, I tried to think of research where the opposite of the anticipated result was found.  Tamoxifen was approved for clinical use shortly after I started my practice in 1975.  It was marketed as an anti-estrogenic alternative to surgical oophorectomy.  Therefore, the concern was that it could lead to osteoporosis.  To test this hypothesis, studies were initiated in 1980 and completed 10 years later.  If anything, Tamoxifen resulted in slight reduction in the incidence of bone fractures.  But: surprise, surprise!!  Increases in endometrial cancer and deep venous thrombosis, occasionally leading to lethal pulmonary emboli, were found.  These complications led to the realization that the drug had estrogenic properties and was in fact a partial, not total, Selective Estrogen Receptor Modulator (SERM).

Quoting Don Miguel Ruiz from The Four Agreements:

“The Third Agreement Is Don’t Make Assumptions.  We have the tendency to make assumptions about everything.  The problem with making assumptions is that we believe they are the truth.  We could swear they are real.”

This is why we do research.

The Doctor As Patient; Lessons Learned

Tags

coaching, community, digital media, elder wisdom, epatients, health 2.0, Just Oncology, legacy, medicine, participatory medicine, social media

On January 7, 2011, my lifestyle was changed forever.  The good news was open heart surgery saved my life.  And no heart damage was discovered.  On the other hand, I had to give myself permission to take care of myself.  What a novel concept!  My entire life had been based on the premise that Richard’s health came last.

At first, I was overwhelmed, which led to anxiety and depression.  The thought that I could die crossed my mind, but this seemed remote and I didn’t dwell on it.  When pain resolved, I was left with fatigue which is slowly improving.  I completed cardiac rehab and went back to the gym after a nuclear stress test was normal 10 days ago.  But even exercise is different now; almost all aerobics and little lifting whereas I used to squat up to 405 lbs. and had the body habitus of a power lifter.  In the distant past I  ran 7 marathons with hardly any resistance training.  Always pushing myself on the extremes; never taking the middle road.

And see a doctor?  Rarely.  No time!  Too busy taking care of everyone else.  Initially my attitude was I’d work until I dropped.  Almost did just that.  Never thought of retiring until now.  Back to work part-time with no plans to work full-time.  But now have more devices than I thought imaginable for 1 human being:

1. Pericardial tissue from a cow for a new aortic valve.
2. 3 bypass grafts from my left internal mammary artery, left radial artery, and right saphenous vein for new coronary arteries.
3. Continuous glucose monitoring by implantable sensors inserted weekly into my abdominal wall.
4. Insulin pump via implants placed every 3 days into various sites allowing continuous basal flow and bolus administration of insulin when eating or hyperglycemic.
5. Blood pressure cuff.
6. Loop recorder inserted into chest wall to monitor for arrhythmias.

This is in addition to multiple pills, each of which has its individual requirements, daily weights, etc.  All this requires time and learning curves, and was unfamiliar to me.  But I found the most frustrating and irritating chore to be calculating the breakdown of ingredients of foods ingested, e.g., carbohydrates, sodium, fats, et.al.  Most of the time, it’s a guess.  Life has become all about monitoring me….continuously!

I was therefore interested to read an article entitled:  “Smart Moves? E-patient Systems Rise Amid Skepticism” by Andrew D. Smith in the current issue of OncLive; 12,6; pp 15-20, 6.11 about disease management systems in oncology.  The concept started with cardiology and spread to diabetes management, obviously pertinent to my experience.  Since several cancers are now regarded as chronic illnesses the concept intuitively makes sense even though triumphs in improved outcomes and/or reduced costs are few so far.  It is estimated that “nearly a fifth of cancer patients already use some form of DM and, collectively, spend $250 million a year on it”.  Annual revenues for the total industry are about $5 billion.

The backbone of DM has been follow-up visits in doctors’ offices or at home, and telephone calls by nurses.  Insurance companies have created Call Centers staffed by nurses for the same purpose.  My wife and I appreciated the 6 weekly home visits and phone calls by visiting nurses; especially my wife who was my primary caregiver and needed reassurance that she was covering all bases.  But cancer care is a bit more complicated since cancer patients are generally older and have all of my co-morbidities that require monitoring and knowledge of drug-drug interactions.  We have entered the era of oral chemotherapeutic agents administered on a daily basis at home.  So danger of lack of compliance has increased greatly.  To address this, the NCI paid Leap of Faith Technologies “to develop a system that uses smart phones, radio-frequency identification technology, and the Internet to ensure patients take their medication”.  The result is eMedonline, which resembles my wife’s iPhone with an attachment which she uses to swipe her client’s credit cards through to pay for their encounters.  Works like a charm.  With eMedonline, a vial of pills is swiped over the attachment to the smart phone whenever a dose is taken.  Preliminary trials have demonstrated increased compliance to >95% and it “is ready for commercial use”.

My 8 year old granddaughter is fascinated by my diabetes care.  She has 2 juvenile diabetics in her class and watched me prepare and inject insulin.  Now that I have the pump, injections are no longer needed.  She hasn’t seen the pump yet, but has watched me upload data from my continuous glucose monitor (CGM) to software on my computer which in turn can be e-mailed or FAX’d to my physician.  But with proliferation of all these systems generating an enormous amount of data, it is imperative we develop new data analysis software to make sense of all this.  I see the data generated by my CGM and it is indeed voluminous.

Finally, in the realm of science fiction are implanted nanoparticles coated with antibodies that detect tumor biomarkers.  It’s coming!  I initially was turned off when my body became a pin cushion and my entire day seemed to be consumed with data entry, device management, ordering of supplies and on and on.  I am beginning to gain better control of all my co-morbities (I hate that term).  I recall the admonition of my surgeon:  “I’ve given you 15-20 more years.  Now don’t screw it up”.  Hopefully, with the aid of newer and more sophisticated DM technologies, I will also be able to say this to my cancer patients, soon.

FDA Avastin Hearings, Links and References

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Avastin, cancer, clinical trials, clinicaltrials, digital media, Dr Just, elder wisdom, FDA, Just Oncology, medicine, oncology, pharma, San Diego, social media, twitter

This blog is committed to the entire field of oncology, health, wellness, evidence based medicine and patient engagement but this Avastin situation is too compelling of a complex story to gloss over. So for those of you with more than headline recap interest in the context as well as arguments on both sides of the issue, here some essential references.

On June 28 and 29, 2011, the Food and Drug Administration (FDA) conducted a hearing on the Center for Drug Evaluation and Research’s (CDER’s) proposal to withdraw accelerated approval of the breast cancer indication for bevacizumab (Avastin). Genentech, Inc., and CDER were the parties to the hearing.

• Docket FDA-2010-N-0621 is available on Regulations.gov. All documents filed or posted in this matter are available for public review under Docket No. FDA-2010-N-0621 in the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, between 9 a.m. and 4 p.m., Monday through Friday.
• You may submit electronic or written comments to Regulations.gov. Comments must be submitted by July 28, 2011. You may also submit written comments to the Division of Dockets Management, (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
• Federal Register Notice

Video Recordings

You may access video recordings of the hearing at the following links:

• Avastin Hearing, June 28: Video Recording
• Avastin Hearing, June 29: Video Recording

Transcripts

You may access transcripts of the hearing at the following links:

• Avastin Hearing, June 28: Full Transcript
• Avastin Hearing, June 28: Condensed Transcript
• Avastin Hearing, June 29: Full Transcript
• Avastin Hearing, June 29: Condensed Transcript

Presiding Officer’s Closing Statement

The Avastin Story, Continued

Tags

Avastin, cancer, clinical trials, clinicaltrials, digital media, Dr Just, elder wisdom, FDA, Just Oncology, oncology, San Diego, social media, twitter

After two days of hearings between the FDA and Roche/Genentech, an advisory committee voted unanimously to revoke the previously granted accelerated approval of Avastin for treatment of advanced breast cancer.  The result has been confusion over the basis for this decision, fear that the drug will no longer be available to patients currently receiving it, and anger that this represents another manifestation of the dreaded “ObamaCare” menace which denies healthcare to save money.  Immediately after the decision was announced, CMS (Medicare and Medicaid) stated they would continue to reimburse for Avastin for the above indication.  To further keep us in limbo, the committee’s decision has been referred to the final arbiter for his ruling which is not expected for 6-8 weeks.

In an effort to provide some clarity for patients and their families, I contacted representatives of Genentech who kindly provided me the clinical trials discussed at these hearings.  First some general comments:

1. The gold standard of clinical research is prospective, randomized, double-blind clinical trials, abbreviated RCT.  Negative features of RCT’s are they are very expensive to conduct (up to $1 billion) and take up to 10 years to complete.  This leads to frustration that cancer research is not progressing rapidly enough.
2. Less understood is that Inclusion/Exclusion Criteria select younger, healthier patients for entrance into these studies, and tend to exclude older, sicker patients who comprise a sizeable number of people seen in community based oncology.  Thus, RCT’s measure the drug’s efficacy, not its effectiveness, putting the test drug in the best possible light.  All 3 of the studies discussed were RCT’s

In February 2008, the FDA granted accelerated approval of Avastin for treatment of metastatic/advanced breast cancer after an FDA advisory committee voted 5-4 to deny such an approval based on a company-supported study showing a delay of tumor growth of 1-2 months with Avastin.   Publication of the E2100 trial resulted in this change to a positive outcome for Genentech and Avastin.  The study involved 722 patients treated with weekly IV Taxol (standard treatment) vs. Taxol + Avastin (experimental treatment) 10 mg/kg IV every 2 weeks.  Addition of Avastin resulted in a doubling (5 months) in time to tumor regrowth and doubling in response rate (tumor shrinkage) from almost 25% to just under 50%.  There were no complete remissions where all evidence of cancer went away, and overall survival was not improved.  Therefore no one was cured.  There was risk in taking Avastin (6 patients died as a result of the drug).  But, the study demonstrated that Avastin had an effect in breast cancer.  So, benefit (efficacy) was judged to outweigh risk, and the FDA granted conditional approval pending completion of 2 other studies that were in progress.

The second trial called the AVADO Trial included 736 patients treated with weekly IV Taxotere (almost identical to Taxol) vs. Taxotere + Avastin 7.5 mg/kg or 15 mg/kg IV every 3 weeks.  Note the different doses and schedules of Avastin.  Whether or not this explains the less impressive results is unclear.  But tumor regrowth was delayed 0.7 months with the lower dose of Avastin, and 0.8 months with the higher dose.  There was no improvement in overall survival.

The final study was the RIBBON I Trial involving 1,237 patients.  Study design was similar (standard arm vs. standard + Avastin) .  But here the similarity ends.  Standard chemotherapy was left up to the oncologist.  Avastin was administered at 15 mg/kg IV every 3 weeks.  Looking at just the group treated with a taxane drug (Taxol, Taxotere or Abraxane) the delay in tumor regrowth was 1.2 months.  And I should point out that the taxane was given every 3 weeks as in the AVADO Study, not weekly as in the E2100 Trial.  Again no prolongation of overall survival was noted, i.e., patients didn’t live any longer whether or not they received Avastin. In this study Avastin was used at the 15 mg/kg every 3 weeks dosing schedule.  I found it interesting that best results were noted when Avastin was combined with Xeloda (about 3 months) since this combination is used commonly in colon cancer where it has been shown to be beneficial.

As a result, an FDA advisory committee voted 12-1 against Avastin’s use in breast cancer in June, 2010.  They accurately pointed out that the above 2 trials didn’t show more than a couple of months delay of tumor spread, and that benefit (efficacy) did not outweigh risk.  By December 2010, the FDA announced plans to revoke approval for breast cancer, but adding that the drug will stay on the market for other cancers as well as “off label” use for breast cancer.  This led to Genentech’s appeal and the current hearings.

It should be noted that RCT’s are designed so that patients receive at least what is considered standard of care.  Thus, all patients received chemotherapy.  They were not denied treatment in order to cut costs.  I find this politically motivated objection absurd.  The purpose of these trials is to identify what works and pay for it.  If all 3 study designs were as close to identical as possible, including drugs used, doses and scheduling, perhaps the results of the second two studies would have confirmed the first.  We are also entering the age of “personalized oncology” where we can identify subsets of patients with certain biomarkers on their cancer cells that predict for response, or lack of it, to a given agent.  In fact, a promising marker for response to Avastin is currently being studied.  Perhaps in the near future we will be able to individualize all cancer treatment.  Wouldn’t it be nice not to need large, expensive and time consuming RCT’s to what will and won’t work in a given patient?

One final note:  All physicians are now expected to practice “Evidence-Based Medicine”.  In order to determine whether or not we are following guidelines appropriately, our government and health plans have mandated we purchase Electronic Medical Records systems.  I estimate the total cost of purchase, update and maintenance of our system to date is over $1 million.   And if we don’t follow agreed upon clinical pathways, reimbursement for providing these expensive chemotherapeutic agents is lowered.  I agree that EMR’s are an improvement over paper charts.  I agree we should practice Evidence-Based Medicine.  But when faced with evidence that Avastin adds no benefit to patients with advanced breast cancer, Medicare states it will still reimburse for it, “who’s zoomin’ who”?

The Avastin Decision: A Deeper Dive Into the Issues

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cancer, clinical trials, clinicaltrials, CMS, Dr Just, elder wisdom, FDA, Just Oncology, medicine, oncology, pharma, social media, twitter

On the Tuesday, July 5th, 2011 broadcast at 8PM Pacific and 11PM Eastern, we re-visit the Avastin decision, and explore some of the issues surrounding the FDA’s choice to ‘hedge’ (a formal decision is pending later this month) the unanimous 6 to 0 panel recommendation to revoke fast track approval of the drug for the treatment of late stage breast cancer.

Some context on the decision can be viewed here, here and here.

To join us live or via archived replay of this exploration of a very timely and rather thorny issue, click here.