Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> For a difference to make a difference it must be a real difference.  Keep this in mind when deciding how much of a difference in safety, efficacy or convenience will be necessary to receive regulatory approval and encourage physicians to use your product.

> FDA based slogans include: Incompetence on your part does not constitute malfeasance on ours.  Also, Failure to plan on your part does not constitute an emergency on ours.

> It is artificial to describe inclusion and exclusion criteria as if they were two separate categories of criteria. The only difference between them is that one set of criteria is expressed in positive terms and the other in negative terms.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

>Internal benchmarking tracks activities and is extremely important to measure progress toward goals. External benchmarking is generally a case of chasing the other guy’s tail. If the external data can be validated then those data will also have value.

> Good ethics and high scientific and medical standards can and should be used as a means to beat the competition.  Regulatory agencies may raise the bar for others developing similar products, if you have raised it yourself.

> Using minimally acceptable criteria for continuing with a product’s development facilitates the best business decisions and helps to avoids games being played on prematurely terminating or prolonging a dying or even a dead project.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Ask yourself whose responsibility it is to create a strategy that will recruit patients. If you said “the investigator” you are wrong. It is the sponsor’s responsibility to create a strategy that will be successful, and if it is not, to readjust it and to apply necessary resources to insure it succeeds.

> Open-label clinical trials often mislead a company as the data obtained have a much greater likelihood of being positive than if the same trial was done in a double blind manner.  This may lead to a company wasting years of effort and millions of dollars until hey recognize that the drug really did not demonstrate efficacy in a true double blind study.

> Insure that any compassionate plea protocols are in your company’s interests. This requires a balance of ethical responsibilities with practical issues. The practical issues include resources required, value of the data obtained and whether your program is being slowed and allowing competitors to catch up or move ahead of you.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Avoid procedure bloat, which occurs when a clinical trial protocol is prepared by taking the previous one and adding some additional tests. This is fairly common as a drug passes through the development path.

> As soon as patient enrollment decreases below projections by a fixed number determined in advance of the trial, seek to learn the cause. Determine if this is evident at all or only some sites (i.e., is it site-specific or protocol-specific).  Either adjust the protocol or change the recruitment strategy. Do not simply add sites until you determine that that is a reasonable action and is likely to address the problem.

> Monitors must understand the intensity and latitude they are allowed in their monitoring activities. Sometimes it may only be necessary to monitor the high enrollers, or a random group of sites in large trials.  In mega-trials it is impossible and not regulatoraly required to monitor these trials as extensively as pivotal trials.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted Bert Spilker

> Work hard to avoid protocol amendments as they consume a great deal more resource than one imagines in staff time to prepare, review and implement them. Some vendors have systems to minimize the numbers of amendments a company will need, by subjecting protocols to multiple internal checks of consistency, and comparisons with other protocols that have been conducted.

> The number of patients available to join a trial drops by about 90% the day a trial begins. This is referred to as “Lasagna’s Law” and is mitigated by using only inclusion criteria that are truly required and by reviewing potential enrollees prior to choosing the site investigators.

> Locate world class experts through professional associations, trade associations, local experts who can tell you the world’s top people in his area, FDA reviewing divisions, FDA Advisory Committee members, other companies in the therapeutic area, and/or literature citations of those quoted most often.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

 

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> To win the hearts and minds of regulators one must first establish the medical need for a new product, i.e., the public health message, and then establish the medical value of your product in terms of how well it addresses the medical need.

> It is legitimate to ask how much it costs to develop a drug when all failures and other costs are included. It is also legitimate to ask how much it costs to develop a single drug excluding other costs.

> Seek a balance between having too many projects where they slow each other and too few where a company risks its ability to survive on a few projects that may or may not succeed and achieve the company’s goals.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Managing research scientists cannot be too heavy handed with the same control mechanisms in place that one uses for development of products.  Medical product development and marketing activities can be more tightly planned and controlled than that of discovery.

> Good, fast, cheap.  Choose any two. You can rarely ever have all three.
  - If you want it good and fast, it won’t be cheap.
  - If you want it good and cheap, it won’t be fast.
  - If you want it fast and cheap, it won’t be good.

> Good data in a few patients are a far better basis to make a decision on, than mediocre data in many patients. This principle is often ignored by those who collect a great deal of uncontrolled data rather than collecting less data from a well-controlled trial.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Exercise great caution in hiring academic or government employees into the industry as leaders, as you may have to spend years of “on the job training” to have them reach the state that many industrial managers are at today.  Many academic and government managers or scientists never adapt adequately in industry, and a company takes a great risk when it hires these people.

> Are the company’s managers mainly living in the past, present or future?  How many are in the present and keeping an eye on the future while planning how to get there?  Where are you living?

> Professional talks and presentations are not like mystery novels where you build to a glorious climax and conclusion. Share the conclusions up front with your audience.  Tell them what you will tell them, then tell them, and then tell them what you told them.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Harmonizing regulations at ICH (International Conference on Harmonization) prospectively before any exist is a lot easier than retrospectively, where three different sets of regulations have to be harmonized into a single whole.

> When dealing with regulatory agencies and the public it is always best to try not to bury issues or problems, but to be transparent with them and discuss how you intend to deal with them.

> We have GCPs, GLPs, GMPs and others. Why do we not have GRRPs (Good Regulatory Review Practices) for how the regulators have to do their jobs in reviewing your applications?

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Data analysis and interpretation of the data are two separate processes, even if they are conducted 30 milliseconds apart by a single person.  Data analysis, however, is usually conducted by a statistician and data interpretation by a scientist or clinician.

> The regulatory cascade consists of laws leading to regulations, which lead to guidelines, which lead to points to consider, which lead to formal recommendations, which lead to informed comments and finally to gossip.

> Without pharmaceutical and biotech research, mankind has little hope of major advances in treating disease, but public support for clinical research is a mile wide and an inch thick.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Business decisions for advancing or terminating an investigational drug in development or a compound in discovery are best made using “minimally acceptable standards.”  These are primarily established by marketing groups, with input from R&D.

> Do your best to eliminate fads and hype in management styles and be skeptical of all claims by vendors.

> Truly great scientists do not generally make great managers. Creative scientists must be encouraged, stimulated and rewarded so they are happy to remain creative scientists.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Steps to shorten drug development lie primarily under the company’s control and the FDA’s role is much more modest in terms of further gains in shortening review times.

> There are three types of discovery or development standards to use as guides to judge data and results: ideal standards that describe the perfect product, realistic or desirable standards that describe what a company wants to have in a new product, and minimally acceptable standards which describe the least acceptable standards for a product that the company is willing to market.

> In theory, new drugs do not have to beat previous drugs in their degree of safety or efficacy, but regulators sometimes forget this and have to be reminded.  If one of the two is not equaled, the other must be far superior to existing therapy.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> The state-of-the-art is often too advanced for the appropriate development level and approach to use.  This is often seen in the ability to measure blood levels at a far more precise level than can be used clinically to make decisions.

> When words like “compliance” or “risk” are being used does everyone know which definition you are using? These and many others have innumerable different definitions for people who approach discovery, development and marketing from many perspectives.

> Using higher medical and scientific standards than required often trumps the competition, as they will be trying to take some shortcuts, and the FDA and others will be likely to raise the bar for approval when they see the standards you are using.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> Sunset clauses for all discovery projects are a useful means to insure the company reviews progress on the project to confirm it should be continued. These may occur every two years or at other pre-assigned times.

> The army has a motto that there is never enough time to do it right, but there’s always enough time to do it over.  A company’s motto must be: We must do it right the first time.

> The state-of-the-art is often too advanced for the appropriate development level and approach to use.  This is often seen in the ability to measure blood levels at a far more precise level than can be used clinically to make decisions.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).

Bert Spilker's Pharma Principles of The Week

Posted by: Bert Spilker

> The perception of medical value of most new products goes through a series of stages from unrealistic optimism to unrealistic pessimism and eventually to a balanced view.

> Time is generally viewed in drug development as the single most precious resource you have to spend.

> There is a spectrum for discovering drugs that ranges from purely rational to that of pure chance or serendipity.

Bert Spilker, PhD, MD is an independent consultant who was most recently the Senior Vice President of Scientific and Regulatory Affairs for PhRMA. He is the founder of  Bert Spilker & Associates (BS&A).