In developing a strategic agenda, the focus will be on five strategies: a market strategy, regulatory strategy and stakeholder strategy (outside-in approach); and a product strategy and a resource strategy (inside-out approach). For each of these strategies, specific strategic thrusts need to be identified that if successfully executed, will lead to achieving your vision and mission. In previous STILE Points, we discussed the key elements of a market strategy, product strategy and resource strategy. In this STILE Point, we will discuss the development of a regulatory strategy.

Most R&D business areas, such as biopharmaceuticals, medical products, petroleum products, chemicals and agricultural products are highly regulated and in some cases, being outright banned (e.g. GMOs). Politics aside, from a scientific point of view, the precautionary principle makes a lot of sense based on age old wisdom and folklore. Starting with Hippocrates’ ancient medical principle of “First, do no harm”; for centuries, our elders have preached that “an ounce of prevention is worth a pound of cure”. “It is better to be safe than sorry”. “Look before you leap”.

Scientific progress is not linear and unfortunately tends to take two steps forward and one step back. The case can be made that the application of science has significantly improved the human condition from extending life spans to feeding the world’s population. On the other hand, the misapplication of science has also caused deleterious effects on mankind and the environment (e.g. thalidomide and organochlorine pesticides).

The New World Encyclopedia defines the precautionary principle as “caution in advance,” “caution practiced in the context of uncertainty,” or “informed prudence.” The precautionary principle has three major components:

  • Anticipate harm and act to minimize potential harm.

This is an expression of a need by decision-makers to anticipate harm before it occurs and an obligation, if the level of harm may be high, for action to prevent or minimize such harm.

  • Onus of proof on proponent.

Under the precautionary principle, it is the responsibility of an activity proponent to establish that the proposed activity will not (or is very unlikely to) result in significant harm. This is an implicit reversal of the typical onus of proof, whereby harm needs to be demonstrated.

  • Absence of scientific certainty not an obstacle.

The precautionary principle is activated even when the absence of scientific certainty makes it difficult to predict the likelihood of harm occurring, or the level of harm should it occur. There is an obligation, if the level of harm may be high, for action to prevent or minimize such harm, with the control measures increasing with both the level of possible harm and the degree of uncertainty.

It is important to note that, although this principle operates in the context of scientific uncertainty, it generally is considered by its proponents to be applicable only when, based on the best scientific advice available, there is good reason to believe that harmful effects might occur.

It is important to understand that people fear that which they don’t understand. Scientific progress of late seems to be accelerating at an exponential rate and advances in genetic engineering, stem cell research, GMOs, climate change and artificial intelligence have the potential to dramatically change the course of human evolution. This fear, along with a growing mistrust of our established institutions, make developing and gaining public acceptance of new products from R&D exceeding more difficult than it has ever been. Given this current climate, your regulatory strategy, and indeed your brand itself must be beyond reproach.

Make the regulatory agency your partner, not the enemy

Given the current climate of public mistrust of scientific advances, regulatory agencies have moved toward vigilant observance of the precautionary principle. It is important to understand that the agency’s mission is not to prevent your product from reaching the market, but to ensure that those products that they do approve or the processes that they regulate meet public safety requirements. This is the same mission that your company has! Thus, when an agency challenges some of your data, instead of viewing them as obstructionist, think of the agency giving you an early warning sign of what you can expect from the public if the product or process makes it to the marketplace.

I have personally been involved in supporting major pharmaceutical product development and safety evaluations requiring FDA approval. In one case, my client spent considerable time and effort working in concert with the agency to develop comprehensive preclinical and clinical protocols to address all the questions that might be raised about the products’ safety and efficacy. We even spent time developing and validating new testing equipment because of some concerns that existing equipment would not adequately generate data that would address the agency’s concerns. Thus, the product was approved on the first IND and NDA submissions.

I have also had frustrating experiences of clients who viewed regulatory agencies as adversaries that must be kept at arm’s length and whose strategy was to conduct the minimally acceptable protocols regardless of the specific concerns that might be raised. Multiple submissions were necessary and the time and effort to gain regulatory approval was onerous. In one case, a potential client hinted at a possible bribe by offering to pay for multiple permitting tests if we would submit only the one with the most favorable results. We respectfully declined and walked out of their office.

While these represent the two extremes, it is important to think both in the short term and long term. There is a lot of pressure brought to bear on the costs and length of time to bring a regulated product to market. This is particularly true of start-up companies whose survival depends on regulatory approval before the seed money runs out. Even more reason to make the agency your ally up front to ensure that there are no regulatory setbacks down the line.

A regulatory strategy must be supported by comprehensive and unbiased scientific data where the potential downside risks are not minimized

In developing a regulatory strategy and the scientific studies to support it, the experimental design must be comprehensive, including studies that may or may not support your product’s claims of efficacy and safety. A good strategy is to try and challenge your product’s efficacy and safety through rigorous testing that includes possible side effects and unintended consequences. This is not a Pollyanna approach. The earlier you identify potential problems with your product, the easier and more cost effective it will be to correct the problems or abandon the product. This approach also breeds trust with regulatory agencies if you are transparent with your experimental design. I’ve seen too many examples of selective studies (with the encouragement of well-intentioned regulatory consultants) designed to present products in the best possible light that fail in the long run, when inevitably, questions are raised that weren’t addressed in the first place.

If your experimental design is comprehensive, inevitably you will experience some positive and negative data. There will be a strong tendency toward conformational bias that could negatively affect your interpretive reports submitted to the regulatory agency. Part of your strategy should be to challenge the data interpretation of your scientific team to develop a broader perspective of the viability of your product. While it is advisable and common practice to present your data in as positive a light as possible, it is important not to minimize the potential for adverse effects or unintended consequences which will be questioned by the regulatory agency and eventually the public.

Develop a transparent communications strategy with the public

In the long run, your product’s success will not be determined by the regulatory agency but the public. As mentioned earlier, you should view the agency as your partner who could provide an early warning of potential problems before your product reaches the market. Given the degree of skepticism that the public has concerning science-based products, your regulatory strategy should be extended to direct communication with potential users. While some of the skepticism is founded on ignorance and fear, there have been mistakes that have been made in introducing new products to the market that warrant public concern.

While developing a good brand has always been an important goal, gaining the trust of the public has never been more difficult. Your communications strategy starts with a values statement that is not just a slogan but a way of life that guides your organizations’ decisions about developing highly effective and safe products. In communicating with the public, you highlight both the advantages of your product and potential risks in a way that the public can understand. While statistics is an important methodology to evaluate risk when dealing with the scientific community, most of the public are ignorant of statistical analysis and have been fooled in the past by false claims. One of my dad’s favorite expressions was “figures don’t lie, but liars figure”. The expression was first stated in 1889 while addressing the Convention of Commissioners of Bureau of Statistics of Labor. Carroll D. Wright was a prominent statistician employed by the U.S. government who said;

“The old saying is that “figures will not lie,” but a new saying is “liars will figure.” It is our duty, as practical statisticians, to prevent the liar from figuring; in other words, to prevent him from perverting the truth, in the interest of some theory he wishes to establish”.

During the entire development process, it is wise to have a transparent communications strategy to keep the public informed. Positive data can be used to promote the potential new product. Negative data and its potential impact should be acknowledged, explained, and actions that are being taken to mitigate or eliminate the negative impacts. The overarching question that should be asked when dealing with ambiguous data is “what can we say that will result in increasing the public’s trust in our decision making.

In our next STILE Point we will turn to developing a stakeholder strategy.