NEW YORK ( TheStreet) -- Last week, I graded my bio-pharma stock-picking efforts during 2012. This week, it's time to look around and ahead. Over the past month, I've spent lots of time talking with professional healthcare investors and listening to company executives. Here are my observations from these interactions. Investor sentiment feels less exuberant than might be expected given the impressive year-to-date performance by the major healthcare and biotech indices. Many investors described 2012 as a difficult year of missed opportunities, undersized victories, and unusually high pressure to achieve index-beating returns. Add to this unsettled dynamic a general sense of unease about the global macro environment and uncertainty over implementation of the Affordable Care Act (ACA), and the result is palpable wariness. From my conversations with investors, I came away with optimism about the future of healthcare, mainly because medical innovation seems to be picking up again. I also heard concerns about hidden risks, largely due to an increasingly brutal commercial environment. And yes, fund managers have been talking a lot about SAC Capital Advisors, allegations of insider trading related to the leaking of clinical trial results, and the impact this may have on healthcare investors and investing. There is a general consensus the U.S. Food and Drug Administration has loosened up a bit. A long list of companies scored drug approvals in 2012, including Onyx Pharmaceuticals ( ONXX) (Kyprolis for multiple myeloma), Medivation ( MDVN) (Xtandi for prostate cancer), Gilead Sciences ( GILD) (Stribild for HIV), Pfizer ( PFE) (Xeljanz for rheumatoid arthritis), Roche ( RHHBY) (Perjeta for breast cancer), Vertex Pharmaceuticals ( VRTX) (Kalydeco for cystic fibrosis), and of course Vivus' ( VVUS) Qsymia and Arena Pharmaceuticals' ( ARNA) Belviq (both for weight loss). Looking ahead, FDA drug approval calendar will remain busy through the first quarter of 2013. Even as FDA is giving the green light to more drugs, selling those drugs successfully remains a challenge. Investors aren't in a forgiving mood when companies make marketing mistakes. Witness the punishing drop in Vivus' stock price after the dismal Qsymia launch, or the cautious statements by Ariad Pharmaceuticals about yet-to-be approved ponatinib in chronic myelogenous leukemia (CML) that sent investors running for the exits.