Part III: 4 Market Access Assumptions Misleading Biotechs

In part three of our four-part series on common assumptions among biotech companies about the HTA process and market access, we examine the third assumption about when planning should begin for global market access.

  1. The data collected and submitted for regulatory approval will be sufficient for HTA and reimbursement.
  2. Just like in the US, market access in other counties happens rapidly after regulatory approval.
  3. Global market access planning begins after phase III clinical trials.
  4. If my clinical results are great, I don't have to worry about cost.

Part III: Global market access planning begins after phase III clinical trials

A founding principle for Context Matters is the connection between clinical trial design with regulatory and reimbursement decisions—the earlier you start thinking about market access the better. Aubagio® offers a great example of the connection of clinical trial design with reimbursement and regulatory decisions.


The pivotal evidence sources used by the EMA and the health technology assessment (HTA) agencies for Aubagio were the TESMO, TENERE, and TOWER trials. These studies compared AUBAGIO to placebo and interferon beta-1a, the standard of care at the time of the clinical trial enrollment. These studies and comparators were acceptable in the EMA regulatory approval. However, for HTA evaluations, NICE also needed an indirect comparison and multiple treatment comparisons to demonstrate efficacy versus newly approved active comparators in their treatment pathway. SMC also considered additional comparators though no clinical evidence was submitted for these comparisons.

This case shows that while there was significant overlap in the evidence sources evaluated, the HTA agencies needed additional information beyond the pivotal clinical trials to determine the effectiveness of the drug compared to their current standards of care. HTA agencies prefer evidence of a direct randomized clinical trial versus the appropriate comparators. As this evidence did not exist, NICE had to settle for an indirect comparison and noted the limitations with indirect comparisons. Aubagio received suboptimal reimbursement. It was recommended with restrictions by NICE and SMC, and received weak ASMR and additional benefit scores which have consequences for pricing in France and Germany.

As shown in the Aubagio case clinical trial design and comparator selection tailored for regulatory approval might not be up to the task of ensuring optimal market access. Based on our analysis of the key drivers of regulatory and reimbursement decisions, we have identified six key questions manufacturers should be asking throughout each stage of a drug's development:

  1. What drugs are on the market and what are the approved indications?
  2. what is the reimbursement landscape for these drugs?
  3. How do the clinical trials' populations reflect the indication of interest for reimbursement?
  4. What are the comparators that reimbursement agencies consider appropriate? 
  5. What is the clinical evidence and outcomes considered by the reimbursement agency?
  6. What was the relative cost-effectiveness of the product and how did this affect the reimbursement decisions?

The first three questions can help manufacturers determine the patient population of interest and the most appropriate comparators within each geography. This leads to the last three questions that focus on the comparators and evidence. 

Historical HTA information can be used to determine the types of clinical evidence sources and outcomes that have been considered in the past. Many of our clients come to Context Matters knowing that they want to include a patient-reported outcome (PRO) but needing to know which PRO to use and how to measure it. Previous HTA advice can help answer these questions. 

These six questions address the key drivers of reimbursement and regulatory approval, forming a blueprint to market access manufacturers can apply in the vast range of decisions from go/no-go through all stages of development.