HTAs: Using Endpoints in Clinical Trials

At the DIA EuroMeeting in March, a look at Health Technology Assessment (HTA) alongside regulatory authority initiatives was presented in a session titled, "Increasing Collaboration Between Payers and Regulators: Can the Convergence Drive a More Efficient and Sustainable Model?"

The discussion, which featured speakers Hans-Georg Eichler, Senior Medical Officer from the EMA; Niklas Hedberg, Head of Department, the Dental and Pharmaceutical Benefits Agency, Sweden (the Swedish HTA); and Sean Tunis, Director of the non-profit Center for Medical Technology Policy in the United States. As noted by Session Chair, Mel Walker, Senior Director Value Expert Engagement & Collaborations, GSK, the goal of the session was to address "as HTA moves closer to launch and assessments being required within six months of approval" there is a clear need to offer more advice in early development of a potential approved drug.

In the EU, the HTA determines whether a drug will be paid for by the government. The United States uses a multi-payer healthcare system, with individual formularies determining the levels to which drugs are reimbursed. However, a clear direction toward the outcomes of health procedures, as well as prescription drugs on the effect of individual health to determine clinical benefit over another is becoming an increasingly important point in healthcare, government, and payer reimbursement discussions.

EMA's status

At issue is how the two distinct and not-equivalent duties of drug regulation and drug outcomes can exist in a similar process. To that end, Eichler presented the EMA's current status of parallel scientific advice meetings, of which seven have been performed. Eichler noted that all seven were with large pharma; all with new mechanisms of action, in the areas of monoclonals, chemicals, and tumor vaccines. What is different between a traditional scientific advice meeting between regulatory and pharma and a parallel regulatory/HTA/pharma meeting?

For the EMA in Eichler's experience, the face-to-face meetings are allotted four hours to the traditional one and a half; and the HTAs offer oral feedback, not a written summary as for the scientific advice meetings.

The discussion of these meetings is how clinical trial endpoint data can also incorporate payer-desired information. For example, can re-hospitalizations be included in the same trial endpoints? That data could be important for regulatory, but is of definite importance for the payers. Or, does the impact on caregivers add value to an outcome of a drug, and then what is the data for that? Eichler noted clear implications for increased use of ePRO. Needed scientific advice on novel methodologies; a new patient-reported outcome; and a new statistical analysis or new biomarker, are all underpinnings of drug development in the future. In the future, he noted, pharma will need to consider the tri-lateral future: EU regulators, scientific procedures, and the HTAs.

Pilot program

Hedberg presented the Swedish perspective on a pilot program between the TLV and the MPA (its regulatory authority) for which they conducted 12 combined advice meetings, five of which were in 2011. From his view, the feedback on the pilot is the best time to seek a joint scientific advice meeting, before entering Phase III; that clinical and regulatory are a vital part of every scientific advice meeting and joint meeting; and that the crucial question is to find the endpoints that are both reflecting patient needs and can be studied.

Tunis' Green Park Collaborative was formed to potentially develop FDA guidance on clinical trials design from the HTA perspective. "The alignment between regulatory and clinical trials is very important to the viability of drug development," said Tunis. "The whole process needs to get much more defined on regulatory and reimbursement decisions."

Tunis told the audience that in the United States, physicians do not believe that the outcomes reported in clinical trials are not outcomes that would be used in routine clinical practice and are not clinically important. Any patient-related or PRO information that is collected during a trial does not make it onto a drug label—so is not necessarily of importance to the regulators—and is of great importance to the payers.

At the end of this session, the message was that a standardization of trial design across therapeutic areas would be more than helpful; that there should be a way to capture the patient voice in a systematic and reasonable way; and that the goal is to have sustainable drug development. Development that can be approved by regulators and help drive cost decisions among the appropriate payers.

—Lisa Henderson