From my perspective, the study makes it even more difficult to figure out which of the many research findings that (briefly) come to my attention every day to write about, and which to ignore. Is this study more interesting, or that one? Well, uh . . . can either of them be replicated?

Authors Glenn Begley and Lee Ellis stressed that they were not out to pillory individual scientists. Indeed, the sheer magnitude of the problem indicates that this is a systemic issue that needs a systemic fix – because journals and funders are valuing perfect stories over accurate data.

In the meantime, though, one of the implications of the study is that far from being riddled with conflicts of interest, preclinical results reported by industry, may be more reliable than those coming out of academia.

This has nothing to do with who’s the better person. Or the better scientist. It has to do with timing. For an academic scientist, a paper in a high-impact journal is a happy ending, the culmination of a lot of effort. For an industry scientist, that paper is also a success – but it is the successful beginning of what could turn into a billion-dollar development effort.

This is not a new view among industry scientists. Several years ago, at a meeting, a friend from a large biotech company and I sat and listened to a speaker hold forth on recent findings that the rate of positive results was higher in papers that come out of industry.

The speaker’s point was that if industry’s rate of positive findings was higher, that was indicative of data massaging. My friend wasn’t buying, though. Instead, she rolled her eyes and snapped, “Well, maybe we run better studies!”

Before industry starts patting itself on the back too hard, let me point out that I am talking specifically about preclinical data. In industry, the problem of selective reporting gets shifted to later in the process – where you can find plenty of stories of whole arms of clinical trials suddenly disappearing from clinical trial reporting and the like.

And so, my point is not that it’s academia’s turn to wear the dunce cap. Companies want to develop good medicines, but they also want to – and need to – be economically viable. Academics want to do good research, but they also want to – and need to – be professionally viable by publishing in good journals and getting grants. Everybody has multiple goals, and the better our system of research manages to align those goals, the better the science that our drugs are based on will be – no matter where that science is coming from.

On Business

“Biotech is all about picking the exception. Granting access to capital to everyone doesn’t strike me as the right idea.”

‑ Bob More, general partner with Frazier Healthcare Ventures, taking an optimistic view on capital constraints. Private biotechs continued to struggle in 2011, raising about as much money as in 2010.

"I think we're going to see a regression to quality."

‑ Jim Healy, general partner at Sofinnova Ventures, on how the venture contraction will mean that only the highest quality companies get funded. Several venture groups pulled out of biotech investing during 2011.

“The take-home message is that it’s easy to build a $25 million company with $100 million cash.”

‑ Tillman Gerngross, CEO of Adimab LLC, on the trend of sliding valuations post-initial public offering. Although a handful of biotechs went public in 2011, the window did not open as wide as some had hoped.

"You can't save your way to success in this business."

‑ Marina Biotech Inc.'s CEO Michael French on the tough financial choices small biotechs must make, such as accepting harsh terms to keep a company moving forward.

“Monday, I was in Chicago, presenting at ASCO. Tuesday, I’m in California, pitching at Goldman (Sachs). And Wednesday, I’m in New York, presenting at Jefferies. How many red-eye medallion miles does it take to get one deal?”

‑ A jet-lagged biopharma CEO, taking a break at the Jefferies 2011 Global Healthcare Conference, and illustrating just how hard biotechs had to work to close financings and partnerships in 2011

On Science

“What happens when the next 10 patients you see require eight different drug combinations based on the mutations in their tumors?”

‑ Outgoing ASCO president George Sledge, on the exponential increases in complexity required to tackle “chaotic” tumors with high mutational load. Personalization of medicine continued to be a theme at ASCO and AACR in 2011.

"You do have to be somewhat of a Talmudic scholar to prescribe this drug."

‑ Lawrence Friedman, member of the FDA Antiviral Drugs Advisory Committee, referring to the regimen for Merck & Co. Inc.'s hepatitis C candidate boceprevir. His comments illustrate the difficulties of putting more personalized treatment regimens into practice.

"The fact that it's inefficient doesn't mean it hasn't made great contributions."

‑ John Mendelsohn, president of the M.D. Anderson Cancer Center, on the National Cancer Institute-sponsored collaborative clinical trials program

“It disturbs me that people are willing to accept this: treating the symptoms and allowing the disease to progress.”

‑ Jerry Colca, president and chief scientific officer at Metabolic Solutions Development Co., on new diabetes drugs

“For every target, almost every company has an inhibitor against it. Medically, as well as economically, we truly need something to get beyond that."

‑ Chiang Li, CEO of Boston Biomedical Inc.

General Wisdom

"A lot of innovation is incremental, not breakthrough."

‑ Glen Giovannetti, global biotechnology leader at Ernst & Young

“I realize it’s absurd to talk about 10Xs or even 5Xs these days.”

‑ Roger Longman, CEO of Real Endpoints LLC

“A combination of good science, good collaborations, good timing and some good luck.”

‑ Mace Rothenberg, Pfizer Inc.’s senior vice president of clinical development and medical affairs in the Oncology Business Unit, on the secrets to the success of lung cancer drug Xalkori (crizotinib)

"You can only set yourself on fire once."

‑ Oleg Nodelman, partner at Biotechnology Value Fund, referring to how pharma stocks tend to jump when they severely cut R&D budgets

"Clearly, there are easier and less insane ways to make a living."

‑ Jim Greenwood, BIO president and CEO, at the BIO 2011 keynote luncheon

The past year brought the biotech sector a mixed bag of news. Some of it was positive – for instance, the FDA picked up its drug approval pace in 2011 and, in some cases, even surprised the most hardened biotech investors by granting approval of some drugs a month or two before their PDUFA dates – while other headlines hailed discouraging trends such as the failure of Prospect Ventures to close its latest round, confirming predictions of a venture capital contraction.

As we get ready to head into 2012 (and possibly an apocalyptic count-down, if those Mayans are to be believed), let’s take a look back at some of the highs and lows of the biotech industry in 2011.

‘Me-First’ Instead of ‘Me-Too’

Biotech execs always talk about tackling unmet medical needs. So it was exciting to see in 2011 the flurry of breakthrough drugs hitting the market. An informal BioWorld poll tagged Seattle Genetics Inc.’s lymphoma drug Adcetris (brentuximab vedotin), the first approved antibody-drug conjugate, as the biggest drug approval of the year, tied with HCV game-changers Incivek (telaprevir) from Vertex Pharmaceuticals Inc. and Victrelis (boceprevir) from Merck & Co. Inc. But other notable approvals included Human Genome Sciences Inc.’s Benlysta (belimumab), the first lupus drug approved in 50-plus years, and Yervoy (ipilimumab) from Bristol-Myers Squibb Co. and Zelboraf (vemurafenib) from Roche AG and Daiichi Sankyo Co. Ltd. as the first two drugs approved for melanoma that actually improved overall survival in clinical testing. And, late in the year, Incyte Corp. scored a win with Jakafi (ruxolitinib), the first approved JAK inhibitor and the first drug for myelofibrosis.

Let’s all hope that trend of “firsts” continues in 2012.

A ‘Nobel’ Death

In a bit of irony (in an Alanis Morissette kind of way), the Nobel committee awarded one-half of the 2011 Nobel prize in physiology or medicine to Ralph Steinman, unaware that the Rockefeller University professor had died of pancreatic cancer three days earlier. Posthumous Nobels are unusual but, after brief debate, the committee wisely decided to allow Steinman to remain a Nobelist. And I’m glad. He certainly earned the title for his discovery of the dendritic cell and its role in adaptive immunity. Plus, according to BioWorld’s science editor, Anette Breindl, who heard Steinman speak in 2007, he was a pretty nice guy.

Best Bang for the Buck?

The biggest M&A deal in 2011 was easily Sanofi SA’s $20-billion-plus-contingent value rights buyout of Genzyme Corp., which followed nine months of often less-than-friendly negotiations. But it wasn’t the best deal for biotech investors. Genzyme shareholders already have lost out on the $1 CVR connected to manufacturing capacity for enzyme replacement therapies Cerezyme and Fabrazyme. Whether they will be able to earn the remaining $13 linked to multiple sclerosis drug Lemtrada (alemtuzumab) is up for debate, and, for the most part, analysts are not optimistic.

If I were to choose, I’d say that Daiichi Sankyo Co. Ltd.’s bid for Plexxikon Inc. and Shire plc’s buyout of Advanced BioHealing Inc. were far more successful M&A deals. Daiichi’s hefty $935 million payment for Plexxikon – a move validated when Zelboraf gained approval in August – came despite only getting U.S. co-promotion rights to the melanoma drug under Plexxikon’s existing partnership with Roche AG. The Shire/ABH deal, meanwhile, showcased the kind of investor returns rarely seen these days. The big pharma firm shelled out $750 million for ABH, a whopping 15x return for ABH’s largest shareholder.

‘Weighed’ Down by Safety

Despite health experts clamoring for new ways to treat the so-called obesity epidemic, drugs aimed at helping people lose weight have not had an easy time of it at the FDA. Industry observers had expected 2011 to usher in not one, but three obesity therapies; instead, all three were rejected by the FDA. Orexigen Inc.’s Contrave got stalled on cardiovascular concerns, while Vivus Inc.’s Qnexa raised worries of birth defects related to one of its generic components and Arena Pharmaceuticals Inc.’s Lorquess bumped up against carcinogenicity concerns. Contrave is set to start a large cardiovascular outcomes study, which would delay its approval until 2014. But Qnexa and Lorquess could have a shot at getting approved in 2012. That’s assuming that no additional safety issues crop up. Given the track record in the obesity space, that’s definitely no guarantee.

The Rough Side of Town

While 2011 had its much-lauded drug approvals (as noted above), the year was not without its disappointments. Two promising areas of research suffered blows – Roche pulled out of the RNAi space, dumping a high-dollar collaboration with RNAi powerhouse Alnylam Inc., while Geron Inc. abandoned its position as embryonic stem cell pioneer to focus on a less-risky cancer drug. But the biggest disappointment of the year – as chosen by 41 percent of respondents to a BioWorld poll – was the slow sales of Dendreon Corp.’s prostate cancer vaccine Provenge (sipuleucel-T). Sales fell way below estimates, and, over the course of the year, Dendreon’s shares have lost about 80 percent of their value. The Seattle-based company has since retrenched and is hoping European approval, now pending, will help accelerate revenue growth. We’ll be watching in 2012.

And the Strange Bedfellows Award Goes to . . .

Probably one of the most bizarre deals ever in biotech was 2011’s short-lived merger agreement between Allos Therapeutics Inc. and AMAG Pharmaceuticals Inc. Having in common only commercially underperforming products – Allos’ Folotyn (pralatrexate) for peripheral T-cell lymphoma and AMAG's iron deficiency drug Feraheme (ferumoxytol) – execs from both firms tried hard to convince investors and analysts of the logic in combining the companies by pointing out a handful of “cost synergies.” But the merger was met with opposition from the get-go and even prompted hedge fund MSMB Capital Management to make an unsolicited bid for AMAG. Unsurprisingly, the deal was voted down by AMAG shareholders. Seriously, what were they thinking?

Well, that’s my list of headline-grabbing biotech news in 2011. But it’s hard to remember a whole year, and I’m sure I’ve forgotten something. What do you think were the biggest events in biotech in 2011?

The first randomized clinical trial was conducted in 1946. British epidemiologist Sir Austin Bradford Hill used randomization to test a pertussis vaccine and a tuberculosis treatment.

But according to an article in the British Medical Journal, the concept of randomization was used even earlier, in agriculture experiments in the 1920s. And even before randomization, controlled clinical trials were taking place as early as 1747, when James Lind conducted an experiment in which groups of sailors with scurvy were given various supplements, including citrus fruits.

Yet at the recent Foley & Lardner Life Sciences conference in San Diego, Pfizer’s Inc.’s senior vice president for patient engagement, Greg Simon, pointed to an even older clinical study. “Book of Daniel,” Simon said, quoting:

“Prove thy servants, I beseech thee, ten days; and let them give us pulse to eat and water to drink. Then let our countenances be looked upon before thee, and the countenance of the children that eat of the portion of the king’s meat: and as thou seest, deal with thy servants.” So he consented to them in this manner and proved them ten days. And at the end of ten days their countenances appeared fairer and fatter in flesh than all the children which did eat the portion of the king’s meat.

Simon’s point was that our clinical trial system might be due for a bit of modernization.

But here’s another interesting fact: after Daniel proved that veggies and water were healthier than meat and wine, King Nebuchadnezzar changed the prescribed diet for the Jewish youths who were brought to live with him. But when James Lind proved sailors with scurvy could be treated with citrus fruits and restored to health within a week, it took 50 years for the British Navy to make lemon juice a compulsory staple on ships, and soon after it was replaced by a cheaper substitute: lime juice.

So while clinical trials may be old, concepts like health economics and generic substitution are not exactly novel – they’ve been a part of the system about as long as the system has been in existence.

The reason? As the authors put it, “cosmopolitan cities now include many individuals whose genetic heritage is drawn from multiple continental origins.” In other words, there’s no such thing as racial purity.

In their paper, which was published in PLoS ONE and which you can find here (http://ow.ly/4YxK6) the team genotyped nearly 1,000 participants of Biobank, a program that collects DNA and plasma samples to aid in genomic and personalized medicine research from patients “representing the diverse communities surrounding the Mount Sinai Medical Center.”

Biobank participants are asked to self-identify as Caucasian, African-American, or Hispanic. But calling yourself something doesn’t make it so: the researchers found that depending on the criteria they used, they could justify racial categories that ranged from subdividing Hispanic samples into three separate groups, to tossing them into one group with the African American samples.

The authors concluded that their data “forcefully underscore the diminishing relevance of the descriptors currently used for the two principle minority groups in the US.” Scientists are sometimes criticized for spending good money to prove what grandma could have told you, and I do remember grandma telling me that you can’t judge a book by its cover. But she never mentioned that you can’t judge a book’s heart disease risk by its title.