A Conversation with Jeff Hall, PhD, Vice President of GenOptix

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biomarkers, cancer, genomics, GenOptix, medicine, novartis, oncology, pharma, social media

By Gregg A. Masters, MPH

On Wednesday’s broadcast of This Week in Oncology our guest Dr. Jeff Hall makes his second appearance on the show. The topic was ‘Biomarkers: their emerging clinical significance in the diagnosis and treatment of cancer’.

Dr. Hall has over 20 years of experience in the life sciences industry, and is currently the Vice President of Clinical Education at GenOptix. He holds a BA in Biology and Chemistry from UC Santa Cruz and a PhD in Biochemistry from UC Berkeley. Dr Hall was the first author on the landmark 1990 Science paper describing the location of BRCA I on chromosome 17q.

GenOptix is division of Novartis. For broader context see webcast by Novartis CEO Joseph Jimenez to the JP Morgan Healthcare conference, and for the deck click here.

To listen to archived replay of broadcast, click here.

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Western Meets Eastern Medicine: Or Ying Meets Yang?

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cancer, clinical trials, CME, digital media, epatients, evidence based medicine, innovation, integrative oncology, medicine, pharma, physician, research, Traditional Chinese medicine

By Richard Just, MD

In today’s China, both eastern and western medical philosophies and practices exist relatively harmoniously.  Patients with minor, usually self limited problems are treated initially with a seven day course of seven liquid herbal preparations taken each day.  If symptoms subside, usually treatment is discontinued.  If improved but not resolved, formula may be modified.  If worse, regimen can be changed and/or referral to specialists arranged.  There are hospitals that practice purely eastern or only western medicine.  But it is becoming more frequent to find hospitals that integrate both disciplines.  Chronic conditions, like cancer, tend to be treated with western techniques, with Traditional Chinese Medicine (TCM) used in a supportive or complementary role.

I was somewhat surprised to hear that the 2 largest cancer problems are breast cancer and liver cancer (mainly the former but not the latter).  Before I left, one of my patients had brought an article to my attention about a low incidence of breast cancer in China  compared to the West.  This may not be the case.  Primary liver cancer, hepatocellular carcinoma), has long been the number one cancer in frequency in the world due to a high incidence of hepatitis, especially in Asia.  This results in chronic active hepatitis, cirrhosis and, finally, cancer.  Even though we stayed at 5 star hotels, we didn’t brush our teeth or rinse our toothbrushes with tap water, and avoided ice.  Sanitation, or lack of it, is an issue.

Everywhere in China, especially big cities, there are forests of skyscrapers.  Private homes are essentially nonexistent as the government owns all the land.  New construction is ubiquitous, so cranes are numerous.  Many of these apartment spaces are empty due to high prices, and those that are bought or rented are shared by several families.  Same with kitchens and bathrooms.  Public bathrooms may lack toilets and simply be holes in the ground.  In some buildings, one bathroom per floor exists.  We saw the interiors of 3 residences.  First, the home of one of four of the farmers that first discovered the terra-cotta warriors outside Xi’an.  Clean.  Very little furniture as you buy empty spaces which you have to furnish yourselves.  But several generations of the family lives there.  Second, a more modest quarters of a woman in the old section of Beijing.  Bathrooms were down the road apiece.  The last was a tiny, single room in what used to be the French Concession section of Shanghai.  Five people slept on one cot.  No mystery why hepatitis and liver cancers are still issues.

Another surprise is lack of mention of lung cancer.  Cars everywhere.  Their gridlock is continuous and called “rush days”.  Mist or fog (mostly pollution) gives a surreal appearance to the landscape of high rises.  Seemingly everyone coughs.  Lots of spitting.  A perfect setup for respiratory problems including lung cancer.  There are several hospitals in major cities devoted to respiratory diseases, however.

An excellent article appeared in the Wall Street Journal, Tuesday, April 3, 2012, pg D4, entitled “Chinese Medicine Goes Under the Microscope” by Shirley S. Wang.  The main topic is a clinical trial studying a four herb combination, called huang qin tang in China and PHY906 in this trial, in combination with chemotherapy to see if effective in reducing side effects of chemo (nausea, vomiting, and diarrhea).  If so, patients might be able to tolerate higher doses of chemo with better results.  Trial design and quality control are issues when doing studies such as these:

One challenge with using herbal medicines is that the ratio of the chemicals they contain isn’t consistent when plants are grown under different conditions.  After testing various suppliers, Dr. (Yung-Chi) Cheng ended up creating a biotechnology company sponsored by Yale called PhytoCeutica to carefully monitor growing conditions to ensure plants from different batches were pharmacologically consistent and to continue clinical development of the compound.

Finally, an article that appeared in the China Daily entitled “There’s More to Life Than Money” by Cai Hong, a senior writer for the paper, cites the first World Happiness Report   released by the Earth Institute last month.  Not surprisingly, the top 4 rated are northern European welfare states:  Denmark, Finland, Norway and the Netherlands.  China doesn’t make the top 100.  One of the benchmarks evaluated is health:

……Increased insurance coverage has not yet been effective in reducing patients’ financial risks, as both health expenditure and out-of-pocket payments continue to rise rapidly.  And there are many reports of disgruntled patients and their relatives attacking the medical staff in hospitals.  Reform of public hospitals is essential to control health expenditure because such institutes deliver more than 90% of the country’s health services.  But Health Minister Chen Zhu said the cost of improving care remains an obstacle, and China is looking to other nations for cost-effective solutions.

While this notice appeared in the WSJ this last weekend:

U.S.-China Pharma: Some big pharmaceutical firms are partnering with Chinese companies in trying to discover the next blockbuster drug.  This Philadelphia conference will include venture capitalists and such Western firms as Novartis and Abbott Labs. Wednesday-Thursday, Hub Cira Centre.  Regular admission:  $1,799.00.

I find it interesting that both the U.S. and Chinese governments are investigating hospitals for price gouging in the sale of drugs. Further, given the emerging cost and access pressures they’re witnessing, might mainland China by eying the health system reform experiment underway in Taiwan?

Trials and Errors – Part II

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cancer, clinical trials, clinicaltrials, FDA, medical education, medicine, oncology, pharma, research, science, social media

By Richard Just, MD

So, the purpose of the Cancer Genome Atlas is to identify all mutations in the most common cancers.  A massive project.  Several maps have been completed including melanoma, pancreatic, ovarian, and lung cancers.  Activation of these mutated genes results in the 6 characteristics of cancer previously listed.  Therefore, it would stand to reason that aiming novel agents at these targets would inhibit growth and spread, possibly cure, cancer.  But which targets to aim at?  For example, pancreatic cancers contain between 50-60 mutations.  To make order out of chaos, the most frequently identified mutated genes are inferred to be causative or “driver” mutations while the rest are “bystanders.”  Also, by recognizing that driver mutations tend to be found in certain ”core” pathways but not others, this further reduces possible targets to a more manageable number.  Between 13-15 pathways, an average of 13, are affected in a typical cancer type.

Getting back to the issue of causation, this month’s issue of Wired Magazine contains an intriguing article by Jonah Lehrer headlined by the following statement:  “Dead –end experiments, useless drugs, unnecessary surgery.  Why science is failing us.”  The title, “TRIALS AND ERRORS”, persuaded me to read on.

The story starts with Big Pharma’s nightmare:  a failed clinical trial.  The drug, torcetrapib, appeared to be a slam dunk in that it lowered bad cholesterol (LDL) and increased the good (HDL) by inhibiting a protein that converts HDL to LDL. Inferred from these facts was that plaque formation would be reduced, which in turn would result in decreased morbidity and mortality from heart attacks and strokes.  In fact, the opposite occurred, and the Phase III trial was terminated.  Pfizer had invested more than $1 billion dollars to develop torcetrapib plus an additional $90 million to expand the manufacturing facility.  The value of the company dropped by $21 billion in 1 week.  Since 40% of drugs fail Phase II clinical trials, and 25,000 volunteers were participating in this trial alone, both the financial and human costs are staggering.  $100 billion is invested in biomedical research annually.

How could torcetrapib fail?  After all, the entire pathway of cholesterol metabolism had been mapped out and the drug’s exact site of action was known.  Sound familiar?  As the author states, “it is a tale of mistaken causation”.  By lowering LDL and increasing HDL, it was assumed that improved cardiovascular health would result.

“This assumption-that understanding a system’s constituent parts means we also understand the causes within the system-is not limited to the pharmaceutical industry or even to biology.  It defines modern science.  In general, we believe that the so-called problem of causation can be cured by more information, by our ceaseless accumulation of facts.  Scientists refer to this process as reductionism……Once we find the cause, of course, we can begin working on a cure.”

Over the years we have learned that our attitude toward cause and effect is perceptual and that causal explanations are oversimplifications.  We have learned to deal with the issue of causation through statistical correlation.  The central concept is statistical significance, which “defines a significant result as any data point that would be produced by chance less than 5% of the time.”  But significant correlation does not necessarily equal cause.  “While correlations help us track the relationship between independent measurements, such as the link between smoking and cancer, they are much less effective at making sense of systems in which the variables cannot be isolated.”  But the human body is extremely complex with inter-relationships between multiple pathways.  Mapping one pathway and identifying all mutations does not reveal interactions between multiple pathways that are connected.  This is why torcetrapib failed.

We are designing new clinical trials.  We are mapping all the pathways of various cancers.  By inference and statistical correlation, we think we have unearthed the driver mutations and core pathways that cause cancers, whose hallmarks have been identified.  Are we setting ourselves up for another torcetrapib?

Trials and Errors

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cancer, clinical trials, clinicaltrials, CME, digital media, medical education, medicine, oncology, participatory medicine, pharma

By Richard Just, MD

The explosion of information in molecular oncology has identified a seemingly infinite number of targets for novel therapeutic agents.  This has spawned the concept of personalized oncology, which has “gone viral.”  However, a disconnect between the very large number of possible targets and the very small number of treatments is now apparent.  In addition, most (85%) of drugs thought to be beneficial in Phase II clinical trials cannot be validated when other labs and institutions attempt to reproduce these results.  And it is still taking up to 10 years and costing over $1 billion to bring a single new agent from the bench to the bedside.  A postulated major roadblock is that Clinical Trial design has not adapted to these new developments.

Maitland and Schilsky addressed this topic in a comprehensive article entitled:  Clinical Trials in the Era of Personalized Oncology; CA, A Cancer Journal for Clinicians; vol 61 no 6, Nov/Dec 2011:  pp 365-381.  Table 1, pg 366 summarizes “Oncology Care and Clinical Trials in the Eras of Population Oncology, Transition, and Personalized Oncology.”  In the areas of Screening, Diagnosis, Staging, Treatment determination, and Assessment intervals, we are headed for molecular-based and individual-based decision making, but we’re still in the transition phase.  As far as early phase clinical trials are concerned, the Population Oncology Era was oriented to maximum tolerated dose (MTD); the Transition Phase is oriented to “optimum biologic dose” and the Personalized Oncology Era to determine the range of tolerable and active doses.   Mid-phase clinical trials use histology and prior treatment-based eligibility in typically single-arm, non-comparator trials in the Population Oncology Era; the addition of some marker-based screening and some randomized controlled trials in the Transition Phase and some trials, histology, and prior treatment-based eligibility with rapid, serial assessments in the Personalized Oncology Era, many with eligibility restricted to tumor marker subsets.  Obviously, the trend is to stratify patients according to their biomarkers and to serially assess for response or lack of it at more frequent intervals to accelerate the conduct of trials.

Another issue is the complexity of the diseases we’re dealing with.  Weinberg and Hanahan proposed 6 “rules” that define the behavior of cancers, the so-called hallmarks of cancer:

1. Self-sufficiency in growth signals:  cancer cells acquire an autonomous drive to proliferate, so-called pathological mitosis, by virtue of the activation of oncogenes
2. Insensitivity to growth-inhibitory (antigrowth) signals:  cancer cells inactivate tumor suppressor genes that normally inhibit growth.
3. Evasion of programmed cell death (apoptosis):  cancer cells suppress and inactivate genes and pathways that normally enable cells to die.
4. Limitless replicative potential:  cancer cells activate specific gene pathways that render them immortal even after generations of growth.
5. Sustained angiogenesis:  cancer cells acquire the capacity to draw out their own supply of blood and blood vessels-tumor angiogenesis.
6. Tissue invasion and metastasis:  cancer cells acquire the capacity to migrate to other organs, invade other tissues, and colonize these organs, resulting in their spread throughout the body.

A Cancer Genome Atlas is currently in process of development for the major cancers to map all these mutations and pathways to hopefully identify targets important in the causation of these cancers.

The Avastin Story: It Ain’t Over ‘Til the Fat Lady Sings

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Avastin, cancer, CME, digital media, epatients, innovation, participatory medicine, pharma, physician, social media, twitter, wellness

After 5 months of deliberation, FDA Commissioner Margaret Hamburg, the final arbiter in the Avastin hearings, decided to revoke approval of the drug in patients with metastatic breast cancer.  At first blush, this event would seem to end the story.  But not so fast!  Even though Avastin cannot be marketed for this indication, it still can be prescribed “off label” as oncologists have done in the past for many agents.  And, this ruling doesn’t affect its use for other indications including colon, lung, kidney and brain cancers.  Medicare will continue to reimburse for Avastin use in breast cancer patients.  But response of private insurers has been variable so far.  All of the above has a familiar ring to it.  The situation is almost exactly the same as it was when hearings ended in June.

We have extensively covered these hearings and the articles on which this decision is based in prior blogs and radio broadcasts.  The data clearly documented that no complete remissions were achieved and, therefore, there were no cures.  In the Wall Street Journal report (WSJ; Saturday/Sunday, November 19-20, 2011, pp. B1-B2), Rep. Sue Myrick (R., N.C.) is quoted as saying:  “When a drug can help save patients’ lives, they should be able to do that affordably.”  Her point was that this decision may result in denial of coverage.  But stating that Avastin saves the lives of breast cancer patients implies a cure, giving thousands of women false hope.  Yes, I’ve personally treated many breast cancer patients with Avastin.  Some have lived months longer than they would have without it.  Rarely years.  But none have been cured.

Coverage of the FDA’s decision has been rapid and extensive.  This morning’s AMA Morning Rounds provides an excellent compendium of what’s been published or aired so far.  I found the last 2 cited sources especially interesting, providing a “point-counterpoint” perspective:

“WSJournal critical of FDA move.  The Wall Street Journal (11/19, Subscription Publication) argued that the FDA’s requiring credible, objective evidence is a subjective standard and criticized the government for interfering with patients’ choices.  The Journal argued that the FDA and medical journals dislike the accelerated approval process for medicines and that its decision isn’t based on Avastin’s side effects but an effort to convey a message that the agency is in charge of pharmaceutical development.  The Journal asserted that the FDA was ignoring the real world and should have allowed Avastin to remain on the market while more was learned about it.”

“FDA decision applauded.  On a blog in Forbes (11/19), Matthew Harper wrote, ‘the FDA decision is the right one, and, more than that, it’s actually good for the drug industry.’  According to Harper, the opposite decision ‘would have made scientists who work at the regulator or who advise it on expert advisory committees more reluctant to give accelerated approvals at all.’  Furthermore, ‘we’re not going to beat cancer by lowering the bar.’  Harper notes, ‘that Avastin costs $80,000 for the average breast cancer patient, and Roche pockets the money whether it works or not,’ adding, ‘we can’t afford to fight cancer with weapons that don’t both shrink tumors and prolong patients’ lives.”

Recognizing these divergent opinions are being read and heard by our patients and their families and friends, how do we advise them about Avastin’s appropriate role in breast cancer, if there are any?    Thoughts of two respected breast cancer researchers, Joyce A. O’Shaughnessy, M.D. and Hope S. Rugo, M.D., are reasonable.  They are stated in the OncLive issue; Vol 12 No 9, 9.11, pg 18:  “Insights on Avastin:  Patient Selection Is Key.”  This selection process should obviously identify both those patients most likely to benefit and those most likely to suffer adverse reactions:

1. At this point in time, we haven’t identified biomarker(s) predictive for response.  Preliminary data suggesting that levels of VEGF-A may identify a subset of patients potentially responsive to Avastin is apparently being investigated.  Until such a marker is identified, it is reasonable to recommend weekly, low dose Taxol + Avastin 10 mg/kg IV q2wks. for aggressive tumors, e.g., triple negative disease.  We have the option of hormonal therapy in addition to chemotherapy for ER+/PgR+ patients, and Heceptin and chemotherapy for HER-2+ patients.
2. By avoiding Avastin in patients at increased risk for complications (recent surgery, planned surgery in the near future, diverticulitis, active body wounds, or uncontrolled hypertension at baseline), safety of administration can be improved.

Don’t blink.  We probably haven’t heard the last of this evolving story.  But that’s as it should be.  Nothing in medicine is exempt from testing to see if it can be done better.

When Less is More – Part II

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cancer, clinicaltrials, epatients, medicine, oncology, participatory medicine, pharma, research, twitter, value based medicine, wellness

In my last blog, I discussed the rationale behind and evidence supporting the United States Preventive Services Task Force’s (USPSTF) recommendation to discontinue routine PSA screening for prostate cancer.  Exceptions might be made in circumstances where men are at high risk.  In 2009, the USPSTF found that screening mammography offered no benefit to women in their 40’s.  Previously, screening was recommended every other year between ages 40-50.  Now it is suggested that women between 50-74 years of age be screened every other year rather than annually.  Pushback to all of these recommendations has been “animated” to say the least.  Finally, the annual PAP smear for cervical cancer has been challenged.  Rather than annual exams, the proposed change is every 3 years.

In her New York Times article of October 29, 2011 entitled:  “Considering When It Might Be Best Not to Know About Cancer”, Gina Kolata asks “What changed?”  Her conclusion is that new information is now available.  In regard to breast cancer, mammography finds the cancer in 138,000 women per year.  But between 120,000 to 134,000 have cancers that already are lethal, or cancers that are so indolent they require no treatment.  In the same article, the chief medical officer of the American Cancer Society, Dr. Otis Brawley, states the way we look at screening has also changed.  “No longer is it just, Can you find the cancer?…..Now it is, Can you find the cancer, and does finding the cancer lead to a decrease in the mortality rate?”  Factor in possible harm that can result from screening, e.g, surgical procedures for benign conditions, and increase in cost, resulting in a benefit/risk ratio that is upside down.

While researchers and clinicians are approaching screening from multiple angles, annual mammography has assumed an almost unassailable status from our patients’ point of view.  To many, screening is equated with prevention of cancer, which is untrue.  Tiring of hearing the unsubstantiated claim that “a mammogram saved my life,” Dr. H. Gilbert Welch and Brittney A. Frankel from Dartmouth conducted an analysis estimating a woman’s 10-year risk of developing breast cancer and her 20-year risk of death.  Their calculations included the added value of early detection and benefits from improvements in treatment.  It was concluded that of the 60% of women whose breast cancer was detected by mammography, only 3-13% were helped by the test.  This amounts to 4,000-18,000 women per year out of a total of 230,000 women diagnosed with the disease.  Conversely, of the 138,000 patients found to have breast cancer as a result of screening mammography, 120,000-134,000 are not helped by the test.  In turn, these numbers pale when put in the context that 39 million women have mammograms each year in the U.S.  So, when they did the numbers, claims that mammography saves lives really are untenable.  The paper by Welch and Frankel was published online on October 24, 2011 in the Arch Intern Med.2011.476.

For abstract, click here.

I agree with my colleagues that some women are helped by screening but the numbers are very low.  Also, the premise that early diagnosis saves lives has been somewhat diminished by improvements in treatment of aggressive and even advanced cancers.  Mammography has certainly improved our ability to diagnose breast cancers earlier as reflected by the marked increase in incidence of carcinoma in situ, i.e., pre-invasive cancer.  And these are not lethal cancers.  Do these facts justify the $5 billion spent on mammograms annually?  I think not.  But the reality is until these recommendations become standard of care, I doubt that many physicians would be brave enough to adopt these as policy in our litigious society.  That’s the sad truth.

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.

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.

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 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.