Drug Truths

A site devoted to teaching about drug discovery and development.

Why Taking “Shots On Goal” Matters to R&D

with 3 comments

Pfizer’s new CEO, Ian Read, recently discussed his plans for reinvigorating the company’s R&D performance.   He spoke of getting “an entrepreneurial sense into the organization with empowered, committed scientists that are focused on what I would call making unstoppable products, shots IN goal not shots ON goal…”

“Unstoppable products,” “shots in goal,” “shots on goal” – what does this all mean and how will it impact R&D productivity?

“Shots on goal” is a term obviously derived from sports.  In theory, you have a better chance to score goals in hockey by taking 20 shots as opposed to taking only 10.  Of course, they need to be GOOD shots and not just wild attempts taken blindly.  Each shot is taken not just to get it on goal, but rather to get it in goal. Thus, it would be a bit strange to hear a hockey coach differentiate between “shots in goal” and “shots on goal.”  Every hockey player takes each shot fully intending to score.

The “shots on goal” philosophy in drug discovery emerged from the realization that, no matter how good your research tools are, animal models such as genetically modified mice are very limited and are not necessarily good predictors of beneficial activity in humans.  It is virtually impossible to predict whether a new discovery drug candidate will be a success or failure.  There are a number of reasons for this.  Does the new compound have an inherent unforeseen toxicological effect?  Is the new mechanism being studied having fewer beneficial effects in patients than expected?  Oftentimes, the true effects of drugs are only learned when they are tested in people.   The unraveling of the human genome was a great boon to discovery scientists; it yielded a wealth of hypotheses as to how to go about treating, or even curing, a variety of diseases.   The problem, however, was that while many of these new targets looked very promising in the lab, it was unclear as to which would translate into effective therapeutic treatments for patients.   In vitro tests and animal testing often provided tantalizing results, but no guarantees.

The “shots on goal” philosophy was applied in the Pfizer oncology labs in the late ‘90s and early ‘00s as a result of the explosion of new targets that were emerging.  At that time, there was a plethora of new ideas to explore in pursuit of discovering new treatments for cancer – some ideas were based on how to prevent tumor cells from metastasizing, others were focused on preventing tumors from growing blood vessels so they would starve themselves and die, some were specific to blocking the processes that caused tumors to grow wildly and still other approaches were even designed to help one’s own immune system fight off this awful disease.   All of these were exciting, viable ideas.   However, it was impossible to believe that any one of these would be a “magic bullet” to cure cancer.  Furthermore, it was impossible to determine which approaches would be superior to others.  The decision was made to find good compounds based on each idea and then take these compounds into clinical trials to see which, if any, successfully treated cancer.   To be successful in the fight against cancer, a number of strategies—or “shots on goal”—were needed.

The ones taking these shots were in the Pfizer cancer discovery group, which grew to over 200 people making it one of the largest divisions in the company.  Over a ten-year period, it produced a number of clinical candidates that explored over 20 of these novel ideas to treat cancer.  While many of these compounds failed to improve the survival of cancer patients, a number of them proved to be very effective.  Two of these compounds have already reached the market, Sutent and Tarceva.   Others, including axitinib and crizotinib, are in the final stages of testing and are generating a lot of excitement in the clinical community.  In fact, it can be argued that Pfizer has the best oncology pipeline in the industry.  Yet, at the start of every one of these programs, one could have rationalized why they might not be successful—or why that “shot” shouldn’t have been taken.

One might think that the “shots on goal” method is a scattershot approach, which, at best, yields a lucky result and at worse, bloats the industry and inflates drug prices.  Actually, it is a valuable R&D philosophy that has its foundation in the belief that you can’t pick winners without clinical data and a product doesn’t become “unstoppable” until its full efficacy and safety profile are understood.  However, for this philosophy to be successful, you must be certain that the “shots” are compounds that have cleared stringent hurdles designed to maximize their potential for success in the key clinical trials in patients.  Just as a hockey coach puts his team in a position to win by encouraging his players to bombard the goal with good shots, a research manager increases his team’s chances for success by exploring multiple promising drug candidates in the clinic.

The “shots on goal” philosophy is one designed for success, meant to maximize the overall productivity of an R&D organization.  Every “shot ON goal” is made with the full intent of it being a “shot IN goal.”  Former Pfizer CEO Hank McKinnell used to say that he didn’t need to go to Las Vegas to gamble – he was already gambling enough on R&D.  The business of successfully discovering and developing new medicines is an incredibly risky endeavor, one that requires a lot of attempts before a winner is found. Limiting your shots by assuming that you can predict winners may ultimately prove to be a flawed strategy.

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Written by johnlamattina

May 26, 2011 at 3:47 pm

Posted in Uncategorized

3 Responses

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  1. I enjoyed your post. This sentence resonated with me: “Yet, at the start of every one of these programs, one could have rationalized why they might not be successful—or why that “shot” shouldn’t have been taken.”
    In my opinion, generating theories for why a cancer drug won’t/can’t work is straightforward. Taking the risk and doing the work to find out whether the drug works is the challenge.

    Laura S

    May 26, 2011 at 4:22 pm

  2. Just wondering: was there ever a fear that “shots on goal” would be perverted/gamed into “hitting numbers”? That is, taking shots that had little chance of success, in order to look productive? (I don’t mean this in a snarky way; I’m curious as to whether, operationally, the notion of “shots on goal” can go awry in the way most every other metric can get twisted up in a large organization.)

    Gil Roth

    August 5, 2011 at 12:56 pm

    • Gil,
      You ask a great question. In fact, our commercial colleagues wondered the same thing: “If R&D was going to reward candidate productivity, how would you ensure that QUALITY candidates entered development and not just compounds to get a score”? We dealt with this by generating Candidate Quality Guidelines, stringent hurdles that drug candidates had to clear before entering the pipeline. I have heard from former colleagues that since left Pfizer that these guidelines were industry best. In fact, our candidate survival success increased as a result of this, at least in terms of more compounds reaching Phase 2.
      – John

      johnlamattina

      August 5, 2011 at 1:10 pm


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