Big Data, Government and Cancer Research: A Benefit for Patients?

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big data, cancer, clinicaltrials, dan munro, evidence based medicine, genomics, innovation, medicine, oncology, social media

By Gregg A. Masters, MPH

On the Wednesday, July 24th, 2013 broadcast of This Week in Oncology at 2PM Pacific/5PM Eastern our special guest is entrepreneur, social media thought leader and Forbes Contributor Dan Munro aka @danmunro.

Dan recently penned a piece for Forbes titled: ‘Big Government Opens Big Database For Cancer Research‘

This catchy headline caught my attention since part of our mission at This Week In Oncology is to eliminate the esoterica from ‘oncology-speak’ and to present the significance of the discoveries, trends and developments in the cancer care and dignostics in plain english for more general consumption.

Much progress has been realized in medica oncology of late with a fair amount of the promisesd upside of ‘personalized [or individualized] medicine’ often pointing to better outcomes via more targeted treatment of specific tumors based on their unique genetic signature.

So called ‘big data’ is in the news as ubiquitous technology, connectivity, the declining costs of massive data dragnets and disease specific mashups affords insights previously inaccessible to reseachers, clinicians and others interested in the diagnosis and/or treatment of oncology.

We’ll get Dan’s takes on his piece and see how he sees the confluence of these trends coming together for the benefits of patients.

To listen live or via archived replay, click here.

The Shell Answer Man

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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.

China Bound: An Appeal to the China Clinical Trials Consortium (CCTC), et al

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cancer, china clinical trials consortium, clinical trials, clinicaltrials, evidence based medicine, integrative oncology, medical education, medicine, oncology, research, Traditional Chinese medicine

By Gregg A. Masters, MPH

Dr. Just will be heading to China this week and has an interest in connecting with clinicians associated with the China Clinical Trials Consortium, other academic or established medical group practices’ specializing ‘integrative oncology’, or solely traditional Chinese medicine for the care of cancer patients.

For a brief personal invitation please watch the video above. Dr. Just’s Twitter handle is @chemosabe1, if you are available during the timeline below and interested in meeting with an American colleague please follow @chemosabe1 on Twitter, he will follow you back and enable direct message sharing. Otherwise an @reply will work as well.

Travel dates and cities are: arriving Beijing, Thursday, May 3rd, and departing Shanghai on Friday, May 18th, 2012.

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.

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.

When Less Is More

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cancer, carcinoembryonic antigen, cea, clinical trials, clinicaltrials, medical education, medicine, oncology, participatory medicine, podcasting, social media, twitter

The longer I continue in practice, the more complex it becomes.  I thought advances in our understanding of the molecular basis of cancer would clarify decision making ; instead answers have led to more questions.  In the spirit of the immortal Henny Youngman:  Take the issue of cancer screening, PLEASE!!

The story of screening for colorectal cancer (CRC) and prostate cancer has many similarities.  The primary screening and diagnostic tool during my training years was the digital rectal exam (DRE).  In CRC the manual examination was (and still is) supplemented with stool occult blood testing.  A positive result usually leads to an invasive procedure, e.g., barium enema or colonoscopy.  Not fun procedures!  And if the test is falsely positive, not only is unnecessary time wasted, cost expended, and anxiety generated, but severe morbidity (bowel perforation) and possible mortality can result.

Enter the great hope:  the carcinoembryonic antigen (CEA).  Finally a simple blood test that would solve all our problems.  It was originally marketed as a specific screening test that should save lives.  But within a short period of time, it was discovered that a positive test wasn’t specific for CRC and a negative test did not always rule it out.  CEA determinations are still useful in following patients treated for CRC to get an idea if they are responding or not.  But, they are not reliable enough in diagnosing CRC let alone reducing mortality from the disease.  Thus, CEA testing is not recommended as a screening test for the general population.

Contrary to the experience with CEA, PSA (prostate specific antigen) screening for prostate cancer has been made available to all middle age and elderly men for 20 years.  Its utility has not been seriously questioned until the U.S. Preventive Services Task Force (USPSTF) reviewed two negative clinical trials and recommended that PSA not be used to screen the population at large.  As with changes in recommendations involving screening mammograms made by USPSTF two years previously, response and pushback has been vocal and immediate.  But, these two trials demonstrated that PSA-based screening of the general population does not save lives.

I found the article ‘Prostate-Cancer Screening — What the U.S. Preventive Services Task Force Left Out‘ in the current issue of the New England Journal of Medicine frames the debate about screening into its proper perspective.  (Allan S. Brett, M.D. and Richard J. Ablin, Ph.D.:  NEJM, 10,1056, October 26, 2011).  They point out that PSA is not a cancer-specific protein and there is a wide variation in aggressiveness across the spectrum of prostate cancer.  Therefore, “controversy and debate about PSA screening were predictable from the outset.”  They cite three issues the panel didn’t address even though they “agree fully with the task force’s analysis”:

1. Every guideline recommends discussing the benefit/risk ratio and individualizing screening decisions taking into account patient values and preferences.  In this era of consumerism, a laudable approach.  However, before the publication of the two trials mentioned above, no data existed to support screening.  So a discussion based on evidence was impossible. “Thus, patients were not really making informed decisions, and office-based discussion of the pros and cons of PSA testing was essentially a charade.  Instead, most patients’ decisions reflected their general concerns about cancer or their general inclination to accept (or resist) medical interventions”.

I lost count of the number of times lengthy discussions ended with patient and family saying that I was the doctor and should make decisions for them.  Even in this age of patient advocacy.  As Brett and Ablin point out, the two screening trials only add to the confusion in that one did not demonstrate any mortality benefit while the other demonstrated a small reduction in prostate cancer related mortality, and there were differences in methodology between them.

1. Management of individual and serial PSA values is inconsistent and unpredictable even within practices.  Physicians are trying to adopt reproducible practices, but “the guidelines are vague precisely because the limitations of PSA screening preclude the kind of rational, standardized, evidence-based algorithm that should inform any routine preventive intervention”.  When one of my colleagues nonchalantly proclaims to practice Evidence-Based Medicine, I remain skeptical.
2. It has been estimated that $5.2 million is spent screening everyone to prevent one death from prostate cancer.  This does not include excessive PSA testing and extra encounters.  So some estimate the actual cost to be more than double this figure.  The authors argue that there are other more pressing uses for this money.  The argument that Black men, who have a higher incidence of prostate cancer than whites, should be screened.  Statistics don’t bear this out since the proportion of deaths from prostate cancer in 2007 was 3.3% in blacks and 2.3% in whites.  The difference is not great enough to justify race related screening, even if we knew how to do it.

A New York Times article entitled:  Considering When It Might Be Best Not to Know About Cancer, October 29, 2011, raises the possibility that more screening may not be productive and could possibly be harmful.  In 2009, the USPSTF, charged with reviewing evidence and publishing screening guidelines, recommended that screening mammograms not be performed on women in their 40’s, and they be reduced to every other year up to age 74.  A similar backlash occurred.  I will review this issue in my next blog.

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.

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.