More To The Henrietta Lacks Story

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cancer, clinical trials, elder wisdom, epatients, evidence based medicine, health, Henrietta lack, medical education, medicine, physician, physicians, research, social media, twitter, wellness

By Richard Just, MD

A few weeks ago, my wife and I attended “A Conversation With David ‘Sonny’ Lacks” at the California Center for the Arts, Escondido.  The event was a sellout with 900 attendees.  As it turns out, most of the colleges and universities in San Diego County designated “The Immortal Life of Henrietta Lacks” as the book discussed by students and faculty this past academic year.  The conversation was sponsored by California State University, San Marcos.  As an added bonus, Mr. Lacks’ daughter appeared with him on the podium.  I had previously attended a similar lecture with the author, Rebecca Skloot, at UCSD.

The story of Henrietta Lacks can be viewed from several vantage points.  As a medical oncologist, and Chairman of the Investigational Review Committee as well as Medical Director of the Research Institute at Palomar- Pomerado Health, ethics in medical research certainly occupies a position of paramount importance to me.  In fact, the book is being discussed locally primarily from this perspective.  Ms. Skloot points out that obtaining ‘Informed Consent’ from patients to do research on their tissue was not required, nor was it considered, in 1951 when Mrs. Lacks’ biopsy was obtained for research purposes.  Mr. Lacks stated he did not feel the family should receive financial compensation for using her tissue for research purposes.  But, Henrietta and the family should have been told that her cells were going to be used for research purposes, what the research involved, and knowledge of the results.  In other words, essentially informed consent as we now require in all patients undergoing clinical trials.

On the other hand, he did feel that the family should receive financial remuneration from the companies that commercialized his mother’s cells by selling them to labs around the world.  This proposal seems fair.  To date, no financial restitution has occurred.

But despite all this, Mr. Lacks maintains an air of dignity that engenders respect.  Throughout the evening, there was no expression of anger or hostility; no complaining.  When asked if he thought that racial discrimination played a role in how they were treated, Mr. Lacks said no, people of all races were treated the same at that time.  Sonny said that although no one from Johns Hopkins has ever formally apologized, they have honored his mother in other ways.

Sonny Lacks was 3 years old when his mother died.  So, he has no direct recollection of her.  In fact, the picture on the front of the book is the only picture of Henrietta in existence.  All that he and his daughter know about her they learned from his older siblings and Ms. Skloot’s research for the book.  When Henrietta was treated, Johns Hopkins was the only hospital in the state of Maryland that treated the uninsured.  Fast forward to the present and this sore is still festering in our country.  Mr. Lacks stated that he recently required stents placed in his coronary arteries on an urgent basis and he, like all the members of his family, is uninsured.  This brought an audible gasp from the audience.  He said he had $100,000.00 in unpaid bills, and he opined that health care should be a right as it is in other countries, not a privilege for only those who can afford it.  This elicited a vigorous round of applause from the audience .  I would add that the number of people in the U.S. who can afford access to healthcare is dwindling also. [Editor’s Note: For specific discussion on the impact in the Black community, see: ‘Blacks See Largest Decline in Health Insurance Coverage.’]

The closest we have to universal healthcare provided by government is Medicare and Medicaid (MediCal in California), see: ‘Medicare: The Basics.’  I recently crunched the numbers in my own situation at age 70 to decide whether or not to convert from my medical group’s health plan (since I’m still working to full Medicare coverage.  Plan A is free and mandatory at age 65.  But I needed Plan B, a Medicare Supplement Plan and Medicare Part D for prescription drugs.  Part B involves an annual fee of $140.00 + monthly premiums of $99.00 + something called “Modified Adjusted Gross Income” (MAGI).  The IRS now sends Medicare a report of my income and a graduated monthly charge is added to my premium.  The monthly total amounted to $259.70.  Added to that is the cost of the Supplement and Medicare Part D.  Then the out of pocket expenses including cost of drugs in the donut hole and now you’re talking “real money.”  Of course, you can opt for a Medicare HMO but choices are limited. So for effect, I will quote myself (drum roll please!):

My conclusion was that being insured does not equate to being covered, and I needed to be a CPA to figure this out.  So, I stayed with my group health plan.

The most poignant moment of the evening occurred when Henrietta’s granddaughter was asked how she felt her grandmother should be remembered.  Her answer:

The gift that keeps on giving.

Not a dry eye in the room.

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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!!!

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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.

Victims No More

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cancer, clinical trials, clinicaltrials, Daniel Kraft MD, digital media, Dr Just, elder wisdom, FutureMed, genomics, medicine, oncology, Pacific Oncology, research, San Diego, Singularity University, social media, twitter

It was 1967.  I was an intern in the UCLA-Wadsworth VA Rotating Internship Program when I reported for my physical as part of the Berry Plan deferment.  For the younger set, physicians and dentists could elect to delay military service until completion of their first year of residency training, and we could elect our branch of service we preferred to serve in.  I chose the Air Force.  On the History portion, I stated that I suffered with asthma since childhood.  Within short order, I was notified of disqualification by the Air Force, my Draft Board reclassified my status to IA, and I was drafted into the U.S. Army, losing my deferment!  I sought legal advice, pronto.

After one year of legal maneuvering, during which time an independent physician certified I should be disqualified from military service altogether, my attorney informed me that all appeals had been exhausted.  I had two options:  go in as a captain or be drafted as a private.  I elected the former.  His parting words were:  “At least you won’t go to Viet Nam.  Not with all the documentation”.  My orders read “Saigon”.  Modifying the Sinatra song:  “It Was” NOT “A Very Good Year”.

I resigned myself to serving my time in Viet Nam.  My wife and one year old daughter would live in Hawaii near her father during my tour.  But, my wife admonished me to try one more time to appeal what was obviously unfair.  So, before we left for Ft. Sam Houston, I humored her and called the Pentagon.  I explained the situation to a Major Baker who was new at his post.  He discovered that all of my records had been shredded!  I sent more copies of my documents to a panel of physicians for its review with no guarantee that their decision would change my orders.

On reporting to Ft. Sam, the entire new group was addressed by the commanding officer.  Sighting his rank (a bird colonel), we greeted him with the loudest groan I’ve ever heard.  But I’ll never forget his advice to us:  “Let’s face it, we gotcha.  You can be miserable all this time.  Or you can make the best of it”.  He went on to say that we would have one year (I had two) at a stateside base during which time we should avail ourselves of all the opportunities to do something other than practice medicine 24/7.  Two weeks later, I was called into the same bird colonel’s office and advised Major Baker had called.  I was not going to Viet Nam!  I’ve said a prayer for Major Baker every night since.  And I did everything reasonable to appeal the decision and then let it go.  No longer a victim.

My two years at the Rock island Arsenal were terrific.  One Sunday I was rounding at a local hospital when a general practitioner (that’s what the terminology was in those days) commented about the then recently enacted Medicare legislation:  “Mark my words.  This is the beginning of Socialized Medicine”.  From that point on, any proposal to organize our practices was met with suspicion.  We were victims of external pressures and resisted most changes to the status quo.

Over time, this attitude has shifted to a more proactive position, dealing with the situation at hand (i.e., making the best of it) and trusting in an outcome that can be managed.  I was impressed by an article entitled:  “Oncology patient-centered medical home and accountable cancer care” by John D. Sprandio, M.D. in the December 2010 issue of Community Oncology, Volume 7/Number 12, pp. 565-572.  This medical home model has been adapted to oncology from primary care as both are assuming more responsibilities for patient care and are under severe financial restraints.  For oncologists, the situation is complicated by “by the perverse methodology of paying physician practices for the drugs they administer after discounts from pharmaceutical companies-a model that has eroded over the past several years”.  A detailed description of the model is provided and successes to date listed, giving hope that we can deal with proposed healthcare reform in a positive manner.  Current and future challenges are discussed.  These include:

1. Assessing and improving value in cancer care.
2. Enhancing physician accountability.
3. Standardizing and integrating clinical care.
4. Encouraging payer collaboration.

The author concludes by stating:  “None of the other efforts that payers are considering provides a sustainable business model for community oncologists”.  It was refreshing to read a well thought out plan addressing present issues rather than the old whining and complaining of the past.  Rather than victims, we become survivors.

The Doctor As Patient; Lessons Learned

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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

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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.

‘HeLa’ Cells

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cancer, Dr Just, elder wisdom, health, HeLa cells, Just Oncology, legacy, medicine, oncology, physician, social media, twitter, wellness

I inherited several traits from my father.  First and foremost was Type I/adult onset diabetes.  But, on a more cheerful note, I am also an avid, if not obsessive, reader.  I remember him sitting on the stairway leading to the upstairs bedrooms reading western novels until early in the morning so he wouldn’t disturb my mother.  That’s me.

Over the years I’ve had many fantastic reads.  One that my father shared with me was “Bury My Heart at Wounded Knee” by Dee Brown.  But none was better than “The Immortal Life of Henrietta Lacks” which I finished a few months ago.  It is a masterpiece written by Rebecca Skloot, a science writer who has written several award winning articles, but this is her first book.  Even though it is non-fiction, the book reads like a historical novel in the tradition of James Michener.  I wish my dad was still here so I could have shared it with him.

There are so many aspects to this story it is hard to do it justice in a page or two.  Ms. Skloot captures the socioeconomic hardships and racial politics endured by Mrs. Lacks and her family, and how they dealt with these indignities as best they could, ultimately with pride and grace.  The author also transports the reader back to vividly portray how medicine was practiced in the era Mrs. Lacks’ cervical cancer was diagnosed and treated.

From a personal perspective, as a medical oncologist who has participated in clinical trials for 36 years, and who has served as Chairman of the Investigational Review Committee at my community hospitals for 22 years, this book has essentially achieved textbook status.  I must confess I did not know HeLa stood for Henrietta Lacks.  I also didn’t know the biography of Johns Hopkins the person, and the history of that hospital.  It made sense that the reason her cancer was so aggressive was that it was an adenosquamous  carcinoma  rather than the usual squamous  cell type.  It was no surprise that her cells subsequently tested positive for HPV 18.  I also found the history of cell culture techniques fascinating as was the economics of the industry that resulted.  So, there was a lot of information that was new to me.

One chapter that was especially moving was 11.  “The Devil of Pain Itself”…1951, pg. 83.  The description of her level of pain was hard to read.  Our ability to manage pain has improved, especially with the advent of Hospice and more emphasis on palliative care recently.   But, last year I attended a symposium on Pain held at UCSD, and the first speaker discussed why no new analgesics have been added to our basic armamentarium of Aspirin and Morphine and derivatives of each for decades.  A sobering thought.

Chapter 17.  “Illegal, Immoral, and Deplorable”…1954-1966, pg. 127, discusses in detail the issue of informed consent, not only as it relates to full disclosure of the nature of the illness and the proposed treatment, but whether or not the latter is standard of care or experimental.   During my fellowship training, I was fortunate to have an attending physician one month who was considered a giant in hematology.  So, I decided to take advantage of my opportunity and asked him how he tells parents that their child has acute leukemia and his treatment recommendations.  His rule was to never use the word leukemia because “they can’t handle it”.  Remember this was 1973-1975 and a paternalistic attitude of physicians was not uncommon then.  I learned a lot from my attending.  The example I cited was a valuable lesson of what not to do.

Chapter 25.  “Who Told You You Could Sell My Spleen?”…1976-1988, pg. 199, brings up a second research topic of who actually owns the tissue after it has been removed from the patient.  Later chapters discuss the current hot topics of ownership of genetic material and stem cell research.  Since my internship and residency training was at UCLA and Wadsworth VA Hospital, and the incident cited occurred at UCLA when I was there, the story brought back memories of those days (and nights and weekends).  It is more personal and memorable for me as a result of this coincidence.

One of the colleges my daughter applied to (over 25 years ago) was the University of Redlands.  Prior to the start of the freshman year, they encouraged incoming students and their parents to read a book which would be discussed with faculty members in a “town hall” meeting.  The book chosen was Robert Pirsig’s “Zen and the Art of Motorcycle Maintenance”.  Even though my daughter didn’t attend that college, I read the book anyway (and loved it).  I wonder if “The Immortal Life of Henrietta Lacks” should be required reading for all doctors, healthcare personnel and staff involved with research?  Hmmm….