Pharma Reform

A guest post in Forbes by Dr.Tom Yates, a UK-based physician, challenges the disclosure statements in two review articles on anticoagulant therapies published in the September 2011 edition of the Quarterly Journal of Medicine.  Dr. Yates also seems to dismiss peer-review as a safeguard and essentially suggests that despite disclosure statements and the peer-review process, any funding by sponsors (pharmaceutical companies in this case) of authors or for editorial assistance for review articles will bias the information presented and will result in an unbalanced assessment of the therapies being evaluated.  He doesn’t critique the papers or their conclusions, admitting that that he is “not an anticoagulant expert.”

In the Forbes blog published letter response to the journal, Dr. Yates’ expectations regarding conflict of interest and the potential for bias are reflected in the following statements:

“In answer to Prof Hobbs’ question [2], I believe it is important that clinicians are able to access review articles on this topic. However, they should be written by authors who have no financial relationship with the companies who make the products under discussion.”

I don’t believe Dr. Yates is alone in his thinking.  I do wonder, however,  if  Dr. Yates and his like-minded colleagues have considered the practicalties of completely eliminating the potential for financial conflict of interest.

1. There are few therapeutic area relevant clinical experts (not just those who are self proclaimed) who could meet his expectations for independence.    As suggested in his statement above, the only people who could publish review articles are those who have never received any financial support from a pharmaceutical company that has a product in the therapeutic category being reviewed.  That would have to include pharmaceutical company sponsored clinical study investigators, consultants, and advisers.
2. Only clinical studies that have been independently funded (self funded, government funded, or funded by an advocacy group that accepts no pharmaceutical industry support) could be included in the publication of therapeutic reviews. To accept results from pharmaceutical industry funded studies done by investigators supported by the pharmaceutical company in a review would further propagate the conflicts of interest and biases inherent in the original publications.
3. Only unconflicted, qualified authors (no potentially biasing financial support from any benefiting organization, be it pharmaceutical companies or therapeutic area advocacy group) could initiate the drafting and publishing of reviews and they would have to seek their own editorial support (including graphics and formatting) at their own personal expense.
4. Peer reviewers for journals would have to be held to the same independence and conflict of interest standards as they have the potential to introduce their personal biases in their feedback and commentary during the peer review process.   Perhaps then these conflicts would also have to be disclosed in the review article as well.

Here are some things to think about in the context of espousing Dr. Yates’ position:

1. There are probably too few independently funded clinical studies that are large enough to adequately provide data to do a meaningful review for any therapeutic category or class of drugs.
2.  “… authors who have no financial relationship with the companies who make the products under discussion” probably don’t have sufficient, statistically relevant, independently funded, personally developed  “controlled clinical data” to support their “independent conclusions.”  Peer-review would have to eliminate any inferences or conclusions that reflect personal biases or opinions from their anecdotal clinical experience that are not supported by statistically relevant clinical data.
3.  As a result of points 1 and 2, very few review articles could be published.  In fact, I’m not sure there has ever been a clinically helpful therapeutic class review article that is completely void of financial conflict of interest and bias as suggested by Dr. Yates.

Unfortunately, history has demonstrated that we can no longer rely on the integrity of investigators, authors, peer reviewers, and editors to assure us that the implications and conclusions in a review article are valid and were not financially influenced.  Therefore, we have to depend on the disclosure statements and rigorous peer-review to mitigate the potential for financial conflict of interest and bias in scientific and medical publications.

Completely eliminating financial conflict of interest might be impossible and even if achieved has its own negative consequences. You would get reviews done by unconflicted experts who have little or no personal,  controlled clinical experience with the products discussed.  This being the case you really have to wonder “are the experts really experts?”   Their conclusions could only be based on their personal interpretation of financially biased industry supported clinical studies, perhaps some small self funded statistically meaningless studies, or worse, their own anecdotal clinical experience.  Where else would they get the data to support their conclusions?

As a result,  I still believe that honest,  full disclosure and rigorous peer review are better solutions than trying to completely eliminate financial conflict of interest. mike@pharmareform.com

The recent disclosures of payments to physicians for speaking engagements, consulting fees, and even royalty payments have come under the scrutiny of industry critics.   Some are probably even embarrassing  to those in the industry.  The publicity clearly has further raised visibility and concerns about the financial influence of the pharmaceutical industry.   Here are 5 ways to eliminate the potential for Pharma Company financial influence:

• To eliminate the financial inducements of speaker fees associated with pharmaceutical industry promotional education programs, medical schools should provide free CME programs to rural or non-medical center community healthcare providers.  To ensure a sufficient number of programs, there should be a national requirement that each medical school affiliated clinician (good speaker, expert, or not) be required to do six medical school sponsored CME programs per year outside their institution  and preferably be given in rural areas.
• Medical School and university affiliated clinicians, in the spirit of independent research, should financially support drug company related trials without pay or compensation from drug companies (no university or institution overhead charges, no pay for staff, no lab fees, etc).  Nominal ancillary pass-through expenses could be reimbursed.  Clinicians should be required to publish in reputable journals  and present the data at major medical meetings without drug company compensation.
• All Pharma requests of Medical School or university clinicians, researchers, or scientists for consulting expertise should be done free of charge (university subsidized) and should be fulfilled by priority of request and existing industry workload of the consultant at the time.  No researcher could consult with the same company more than a cumulative 6 months in a given 5 year period of time. All related travel expenses, including meals provided, would be paid by the university and anything that resembled an exotic meeting location would avert attendance by the consultant.
• Medical School affiliated clinicians and university researchers or scientists could not benefit from any royalties or payments related to their inventions.  All such payments would go to the Medical School or university general research fund to support ongoing research.
• If Medical School or university affiliated clinicians or executives, feel compelled to sit on Pharma Company Boards of Directors or Advisory Boards they should do so without compensation (this includes no stock or stock options).  They should also pay their own expenses to attend meetings, including paying for meals provided.

You are probably saying, “These make no sense.”

Yet, industry critics sensationalizing the highly paid speakers and consultants or Medical Schools and universities going after sales representative pens, sticky pads, and free lunches are, in a very self serving way, distracting the public from the real financial influence of the pharmaceutical industry.

If they were serious about eliminating industry financial influence it would mean giving up hundreds of millions, if not billions of dollars of industry support and compensation subsidies for Medical School and university affiliated faculty, staff, and their research programs.   Because they have no other financial sources to replace the magnitude of this funding, Medical Schools and universities (and industry critics) have to ignore the fact that these financial subsidies from the Pharmaceutical Industry can have a far greater influence than a sticky pad, a free lunch, or a couple thousand dollars in speaker or consulting fees.   mike@pharmareform.com

A change of heart at Stanford Medical School allowed it to accept $3 million from Pfizer for CME after having publicly denounced the inappropriate financial influence of industry on CME. The draconian ACCME decision regarding AHA (American Heart Association) meeting restrictions on industry presentations could have had serious financial implications for AHA if they had not defended their peer review screening process and the desire to have industry scientists on their programs.   Although there was considerable support for the research information sharing value of industry participation,  I also suspect a considerable amount of industry financial support could have been at risk including major sponsorship commitments, exhibit space sales, and other marketing opportunity fees.   And now the state of Massachusetts is having second thoughts about restrictions they have placed on pharmaceutical sales representative activities (e.g., pens, sticky pads, and free lunches) because of the negative financial impact the restrictions are having on local businesses.

Are we getting to a point where the level of ethical and conflict of interest concerns about pharmaceutical industry influence will be moderated more by the level of financial impact than the convictions of those imposing the restrictions?

Here is one way to keep people honest about their ethical and conflict of interest considerations when restricting pharmaceutical industry activities.

It is the right of these groups and organizations to regulate and even ban pharmaceutical industry activities.  But,  if industry influence on prescribing and concerns for conflict of interest are seen to be detrimental to patients and are the basis for these decisions to preclude the industry from participation, then the restrictions and the need to avoid these influences should apply in principle to all members of that group or organization as well.   There are now a sufficient number of cases which demonstrate physicians and scientists are not immune to breaches of integrity and have been equally responsible for creating these concerns for biasing information about prescription drugs and participating in the creation of conflicts of interest.  Therefore the restrictions should apply to both sides of the activities of concern.   Here are some examples of how they should apply to Massachusetts or for any other organization with pharmaceutical industry restrictions:

• No physicians in the state of Massachusetts (faculty member of Stanford or AHA member, for example) should be allowed to accept any fees from industry, even for legitimate advisory, consulting services, or Board of Directors participation.  These individuals are selected for their expertise and they could be influenced by these payments (more so than a free lunch or pen).  More importantly, these individuals, because of their expertise and influence, have the capacity to influence (pass along biased information) far more physicians in private conversations and even in non-industry sponsored programs.
• Massachusetts licensed physicians and other healthcare providers (or from other restricting groups) should not be allowed to participate in any industry sponsored meetings or conferences.  This includes any national society meetings or conferences or scientific meetings sponsored by industry.  A pharmaceutical company merely being seen as a sponsor could favorably influence a physician about their views of the company and their products. Not to mention the exhibit area influences they would be subjected to.
• No medical meetings or events sponsored by the pharmaceutical industry should be allowed to be held in Massachusetts as this would be encouraging the very behavior (inappropriately influencing physician prescribing) and activities they are trying to curtail with their restrictions.
• Clinical studies are powerful ways to influence prescribing, especially for new products.  Therefore, clinical studies should not be done in Massachusetts (or other restricting institutions).  If they are done they should be done for no fees with only nominal, non-compensation related administrative expenses being reimbursed.
• Research grants and funding have the potential to favorably influence prescribing practice, especially if the data are published under the reputable name of the institution.  Therefore, no industry sponsored research should be conducted at or in institutions other than drug, life science, or biotech companies within Massachusetts.  No industry sponsored research should be allowed at any state facilities or their affiliates.

While these may have significant negative financial implications for individuals, businesses, and organizations, this mutual implementation of restrictions would preserve the integrity of decisions made to avoid conflicts of interest and limit the perks and financial influence of the pharmaceutical industry on prescribing practices.  In fact, these restrictions would have a far greater impact on assuring the elimination of industry influence than taking away pens, pads, and free lunches.

I suspect the negative financial impact will probably be far too great to allow ethics and decision making integrity to prevail in most situations .  As long as it makes financial sense for Massachusetts or other organizations,   the restrictions and expectations for compliance will be one way (only the industry must be controlled and comply) and will not really be driven by the ethical and integrity convictions of those imposing the restrictions.

mike@pharmareform.com

The pharmaceutical industry has created market perceptions, right or wrong, that have been transformed into market expectations.   Like for any business meeting market expectations is a critical success factor for the pharmaceutical industry.  There are however, some expectations that are ill founded and meeting these unreasonable expectations could mean financial disaster to pharmaceutical companies.

Reasonable market expectations are best addressed by the consistent actions and behaviors of the company over time.  Unreasonable market expectations, on the other hand, require understanding of the source, empathy, patience, and clear consistent communications to help the market better understand why some of their expectations are not practical or not in the best interest of patients.

The industry must effectively demonstrate that they are delivering on the reasonable expectations, before the market will be ready to accept explanations for why the unreasonable expectations can not or should not be met.  So what expectations are reasonable and which ones might be considered unreasonable?

Reasonable market expectations of pharmaceutical companies:

• To bring safe and effective innovative new drugs to the market at fair prices
• To not have to pay premium prices for products which can not be clinically differentiated in a meaningful way that matters (comparative value)
• To moderate pricing based on substantiation of the pricing rationale with data and clinical information that demonstrate the value of the drug treatment
• To make certain physicians and patients understand the risks associated with product use. Never putting patients at undue risk for the sake of selling more products.
• To assure regulatory compliance in development, manufacturing, and commercialization (marketing and sales). Respect that prescription drug regulations are intended to protect patients from undue harm.
• To act with integrity in support of legal and ethical business practices
• To be transparent in financial support of societies, patient advocacy groups, and other information sources so as to not secure deceptive implied endorsements for products
• To be forthcoming and take decisive action to protect patients when concerns for safety arise, even if it means a temporary negative impact on sales
• To hold executives accountable for their organizations actions and behaviors

Unreasonable market expectations:

• To sell innovative new products at generic drug prices
• To operate pharmaceutical companies as “non-profit” organizations
• To not advertise or promote products for appropriate uses
• To rely on medical school and professional society medical education programs to educate physicians about drug treatment, especially new products
• To execute clinical studies or access clinical expertise without paying investigators, advisors, and consultants reasonable fees (absolute “conflict- of- interest”  free)
• To develop treatments for small patient populations and not charge prices which allow for a profitable return of investment
• To blindly write checks for product liability claims when the risks have been clearly delineated in product information, advertising, and promotion.

Doing a good job of meeting the reasonable expectations will mitigate the importance of and insistence on many of the unreasonable expectations in the evolving new healthcare market.

mike@pharmareform.com

No single event, single offense, issue, or individual company can be identified as the source of or considered responsible for the market distrust of the pharmaceutical industry.  This has been a cumulative affect over the past 30 years or so of modern day Pharma.  It is important to identify, recognize, and acknowledge the sources of distrust before solutions can credibly and effectively be formulated.  Here are the 5 major sources of market distrust of the pharmaceutical industry:

1. Lack of honesty and full disclosure about product information (Corporate, Marketing, Sales, and Scientific integrity issues)
   1. Not disclosing, not acknowledging or downplaying potential serious adverse reactions and side effects (e.g., many including  Fen-Phen, Vioxx^®, OxyContin^® , Ketek^®)
   2. Exaggerated product claims in marketing or in sales presentations…especially comparative claims
   3. Scientific data manipulation to highlight benefits, exaggerate efficacy while carefully downplaying side effects and adverse reactions
   4. Deception in advertising (paid actors or celebrities to project credibility as they play healthcare providers or miraculously recovered or satisfied patients)
2. “Off-label” promotion (e.g., many such as Neurontin^® and Bextra^®)
   1. Companies not willing to spend the money to prove the claims but willing to encourage physicians to subject patients to uncontrolled experimental use
3. Questionable physician payments, inducements, and “conflicts of interest”
   1. Extraordinary Speaking fees and resort location training programs
   2. Excessive consulting fees, including suspect clinical study payments
   3. Board of Director fees (hundreds of thousands of dollars)
   4. Office practice meals, tchotchkes, and other perks
   5. Expensive meals, cultural or sporting events (e.g., Broadway shows, golf outings) for physicians and other healthcare providers who can influence prescribing
4. Pervasiveness of industry influence on scientific and medical communications
   1. Promotional programs presented as CME
   2. CME program development and sponsorship
   3. Medical Science Liaisons as safe harbors for scientific exchange of product information
   4. Publications, including sponsoring ghostwritten articles and books
   5. Journal advertising in medical journals
   6. Scientific and medical conference participation and exhibits
   7. Internet medical information sites
5. Pricing practices
   1. Pricing fraud (especially as it relates to Medicare and Medicaid)
   2. Unsubstantiated high prices (lacking credible rationale or cost benefit data)
   3. High price increases (recent 9.3% increase compared to -0.3% for general inflation (CPI-U)

This is now a complex, multifaceted, and time entrenched distrust. Can the industry afford to ignore it?  If the industry or a company decides to work on this, what should they do?  What can they do?  Stay tuned.

mike@pharmareform.com

This story is making it around the newswires and industry blogs. This may not have even been a story if Stanford had not taken such a hard stand previously about the pharmaceutical industry financial influence. You can go to the Stanford website for their release. http://med.stanford.edu/ism/2010/january/cme.html

I couldn’t resist commenting myself;  so here is what I have posted on some sites:

Unrestricted grants are not a new concept. I’m not sure how, or if, this is different. While Stanford control and lack of Pfizer input on specific content may be the implied distinction being proposed here, that has been the intent and practice of many unrestricted pharmaceutical industry grant supported programs including many ACCME programs in the past. Without more transparency about the negotiations that took place surrounding this grant, it is hard to understand how identifying “programs of mutual interest” with “milestone” payments hasn’t already or isn’t going to influence what topics are going to be covered in these Pfizer sponsored Stanford programs.

It appears that Pfizer merely found the price point at which Stanford was willing to compromise its previously stated position (Stanford Report dated September 13, 2006 “New Policy Limits Drug Industry Access”) that “industry-directed funding may compromise the integrity of these education programs”. The $3 million seems to have also moderated Dr. Pizzo’s concern about “the pervasive presence of the pharmaceutical industry in the medical profession” and his desire for Stanford educational activities to “not be influenced by any kind of financial industry support.”

A couple of things must have happened. Either Stanford could not find sufficient alternative sources of funding for their continuing medical education department and/or the $3 million was just too hard to turn down.

I guess everything still has a price; you just have to figure out what it is. This relationship based on a $3.0 million grant does not help move CME forward for the industry, academia or healthcare providers. It provides validation for those who continue to be concerned about financial influences of the industry. Pfizer merely proved that even Stanford can’t resist…when the price is right.
mike@pharmareform.com