Another harbinger of change for me at the Summit was its coincidence with my transition into Twitter. I went intending to tweet each session, but soon became absorbed in the tightly packed agenda, which ran with few stops during the main day-and-a-half of the event. It was all I could do to keep up with taking notes, so I cheated: waiting until I got home to do my tweeting. The account that follows is thus organized around some of the tweets — my own “takeaways” from the many presentations, roundtables, and open discussions in this lively congregation of R&D leaders from pharma and biopharma companies of all sizes.
TWEET Novartis Pharma Head David Epstein at R&D Leadership Summit: immortal jellyfish may be key to Pharma's future in anti-aging Rx
Epstein gave the keynote address on the first morning of the Summit, mostly an upbeat but realistic forecast of the industry’s future that he cautioned against believing too strongly. He concentrated on four areas of special promise for pharma R&D: disease pathways and “critical nodes” as therapeutic targets; cancer treatment; gene replacement; and reversal of aging. His central theme was the surprising ways R&D breakthroughs happen, starting with new insights into biology often triggered by the most unexpected discoveries. Aging yielded his most striking example: a tiny jellyfish that scientists now know ends its adult life by sinking to the bottom of the sea and turning into an amorphous mass of DNA, then once again into a polyp, which grows back into a fully functioning adult, thereby skipping death entirely. If life has any lessons to teach us about the aging process and how to revert it, the immortal jellyfish may hold them.
But Epstein outlined the chief capabilities that industry will need to turn such scientific breakthroughs into commercial ones: powering clinical trials with preselected patients; combining diagnostics and therapeutics; next-generation gene sequencing; and constant adjustment to an accelerating expansion of new technologies. Regulators will change in kind, he said. “Forget the label — market approvals and clinical trials will be based more on which genes are activated than on classic disease indications.”
Perhaps you can’t patent a jellyfish. But if you “invent” new knowledge about it, and use that knowledge and more to produce a novel therapy, the knowledge can become valuable property to be parlayed into business investment and growth. The simple equation has logical virtue, but the public and various interested parties don’t automatically accept it. Echoing a common theme among many Summit speakers, Epstein argued that the industry must address those parties with urgency, using persuasion and education to win their support for IP protection in the life sciences.
When all payers pay for response to Tx, not use of Rx, how will Pharma fare? Companies - or payers - ready to play that game?
Nothing sharpens the mind faster in this industry than a reimbursement challenge. Until relatively recently, such challenges were typically one-on-one affairs: a single product or product use at stake. Now much of the United States will be converting, albeit slowly, to a pay-for-results system based on whether and how much patients respond beneficially to a given treatment regimen. Scary, huh? Steady on — because the movement will happen state-by-state and operate through private insurers and managed care, it will likely be glacially slow, say, on a timescale similar to drug development.
Maybe that’s why the pay-for-response challenge propelled numerous areas of discussion at the Summit, from the dearth of new primary care medicines to the changing designs of clinical trials. On the one hand, the FDA received much blame for impeding primary care development by requiring more and more safety-related outcomes studies, some of which, like “suicidality,” often seem inappropriate and impractical for developers. On the other hand, the R&D leaders appeared not resigned, but enthusiastic about taking a more holistic approach to patient health (see below).
My biggest worry, however, is that focusing on individual patient benefits will fragment development into ever smaller niche areas. Already, the lion’s share of the industry’s pipelines consist of mouse-size products designed to carry elephantine price tags. Applying the concept of gene-activation over disease indication may prove the only way out of the conundrum for R&D, regulators, and payers. Rather than defining a drug (or drug-device) by the disease it treats, we would characterize it by action/benefit in whatever patients fit the genetic or biomarker profile.
"Do you feel better?" That is the basic question Pharma must ask patients to know true Rx/Tx outcomes.
A number of people, including our chief editor Rob Wright, retweeted this one. It is one of those simple and direct statements that carries a large charge of implications. A speaker or audience member actually said it, intending to summarize previous discussion, but even alone it comes across as intuitively correct, if highly problematic. R&D traditionally keeps its distance from patients, as do the people who directly care for them. Sound psychological and scientific reasons for the distancing exist. Yet, if the industry’s customers will only reward demonstrable patient benefits, researchers and business people must have a more intimate view of how their products really affect patient experience in treatment, and in the context of their symptoms, co-morbidities, and total response. Angels as well as devils await in the details; patients may well benefit, but demonstrating the benefits in well-designed, efficient clinical trials will raise big hurdles for developers.
Most drug discovery data is not reproducible, costing Pharma R&D $Bs in retesting or failure later.
Academic researchers caught most of the flak for this startling fact: more often than not, biomedical discovery data arrives at a company’s doorstep in slipshod condition, with major flaws such as poorly selected data points, faulty data collection and recordkeeping, and unwarranted analysis. Unlike many other disciplines, biomedical discovery research typically follows no standard framework. Often, the experimental design is exceedingly arcane, and no other lab can reproduce the procedure or results. And by the time a company determines validating the data is impossible, it may have spent a great deal of money doing so. Two relatively new documents throw light on the subject and offer direction toward common data standards that could ameliorate the problem: “Handbook: Quality Practices in Basic Biomedical Research (QPBR), WHO, 2006; and “Best Quality Practices For Biomedical Research In Drug Development,” American Society For Quality (ASQ), 2012.
Complexity inverse to performance in clin. trials. Protocol amendments oft-disruptive & unrealistic.
I heard this idea in many forms. As discussed, trials grow more and more complex as outside demands for information increase. But there is also an internal dimension. Legacy processes resist change — change at a scale needed to speed trials. Outdated or superfluous procedures, endpoints, and other elements are boiler-plated from previous trials into new protocols. But there is also procedural and endpoint “creep” as the protocol writing proceeds, typically to establish scientific context, maximize statistical data, apply long-standing operational policy, and manage risk. Protocols might be a significant area where R&D can achieve greater efficiency and power in clinical trials. Also, my editorial ears snapped to attention when someone said something like this tweet: “Good clear writing: what trials protocols need most. Write so everyone down the line can understand.”
Big Pharma consensus: CROs grown up into partners, but no 1- stop shopping; outsourcing more than 50% R&D risky.
In truth, a convincingly universal opinion at the Summit was that the most senior CROs, as well as many smaller ones in special areas, have matured into reliable, well-equipped “partners” in drug development, having made large improvements in recruitment, data management, and specimen handling. A large company may outsource the most for late-stage trials, in therapeutic areas new to the company or to increase global reach; a small, specialized company will likely need more CRO help in the earlier stages. But small companies beware: “watch the contract” with CROs for change-order and other incidental fees. Some small companies insist on, and get, fixed-price contracts covering all incidentals.
What happened? Most recent clin-trials reforms backfired. Keep your eye on PI, site, and data quality.
The issue of previous reforms in clinical trials came up late in the Summit, with a presentation by frequent moderator Ken Getz of Tufts CSDD. The most recent wave of reforms — such as expansion of eTrials, globalization, running more trials in emerging markets, and greatly boosting the number of sites while shrinking their average size, and outsourcing site management — were intended to lower cost, spread risk globally, speed trials, and improve patient/PI retention. Yet the reforms apparently caused the opposite effects — or perhaps unluckily coincided with them.
“In any case, a reboot is needed,” said Getz. Not that all the reforms were wrong, but companies must also pay close attention to the quality of their investigators, as well as the resources and skills at all its sites and the data that comes out of them. My interpretation: outsourced is not out-of-mind.
Hey, that sounds like the beginning of a good tweet. But even the best tweet never seems to say enough, and the same may be said of this report. Anyone with me at the Summit will see great gaping holes in this coverage, which only serves to prove there’s no substitute for being there. In fact, the air of privacy at this meeting is refreshing and productive. But I also saw evidence of an industry still growing up, though now far from the former days when walls isolated companies and their R&D from the outside world.