OBJECTIVES: In the US, HTA bodies not responsible for reimbursement decision-making are making coverage and pricing recommendations. As a result, biopharmaceutical manufacturers must anticipate reimbursement decision-making a decade into the future and not just among national insurers or managed care companies, but based upon reviews by third parties. To discern how these third-party organizations’ reviews compare to national HTAs, ICER’s report on insulin degludec was compared to evaluations by national HTA bodies. METHODS: ICER, IQWiG, NICE, and Swedish Health/Welfare reports/guidelines examining insulin degludec for Types I and II DM were compared by (1) comparators; (2) clinical outcomes examined; (3) data sources; (4) final recommendations. RESULTS: (1) Comparators: Decision-makers exhibited variability in selecting comparators: ICER examined insulin glargine or detemir; NICE also allowed sitagliptin; IQWiG deemed human insulin or human insulin plus metformin as comparators. (2) Clinical outcomes: Change in HbA1c and nocturnal hypoglycemia were the outcomes of interest for all reviews. (3) Data sources: Based on published data-alone, ICER provided a recommendation of added benefit for Type II DM. However, other HTAs declined to provide any recommendation based on both published or unpublished data due to inappropriate and/or missing data. (4) Final recommendations: None recommend insulin degludec for patients with Type I DM; while ICER and NICE found added benefit or non-inferiority in patients with Type II DM. CONCLUSIONS: This study found that substantial differences exist between approaches used by ICER and traditional HTA bodies. Traditional HTAs have been subject to heavy criticism and do not necessarily represent a “gold standard.” ICER decisions are based on a systematic review of the peer-reviewed literature, which differs from the traditional method of a systematic review in addition to manufacturers submitting both published and un-published materials. Timely publication of trial data is becoming increasingly important to successful evaluations by traditional HTAs and emerging independent evaluators alike.