Written by Paul A Corris
Introducing the Innovative Drug Development Initiative
The Pharma Task Force, established in 2015, has enjoyed an energetic childhood under the direction of Sylvia Nikkho, Peter Fernandes and Paul Corris, having established three linked and mutually supportive projects. It has matured rapidly into one of the four strategic ‘backbone’ activities of PVRI. As such, its new name will be the ‘Innovative Drug Development Initiative’ (IDDI), which describes its purpose more precisely; the IDDI’s mission is to create and provide a dialogue platform, where there is free and open discussion between academia, patient representatives, regulators and pharma industry on innovative development strategies.
The three inter-linked IDDI workstreams comprise novel:
- Clinical Trial Endpoints, led by Olivier Sitbon and Sylvia Nikkho,
- Clinical Trial Design led by Jim White and Peter Fernandes, and
- Biomarkers led by Anna Hemnes and Lawrence Zisman.
The overarching and strategic work is led by Paul Corris (member of the PVRI Executive Board), Peter Fernandes and Sylvia Nikkho within the IDDI Leadership Team.
The recent European Respiratory Society meeting, held in Paris in September 2018, offered an opportunity for IDDI members to meet face to face in a session convened by Sylvia Nikkho, with those unable to attend in person joining via telephone. The meeting opened with a welcome from Gérald Simonneau and Olivier Sitbon in their home town.
The meeting was well attended by 21 representatives from academia, patient organisations, regulatory agencies and pharma industry development functions. Presentations and discussion took place relating the work of all three streams.
The section on novel endpoints, chaired by Sylvia and Olivier, discussed the potential role of utilising a risk score as an end point in trials and a presentation was given by Raymond Benza’s group on new developments with the REVEAL score. There is the ongoing machine learning ‘Pulmonary Hypertension Outcome Risks Assessments (PHORA)' project being applied to the data to refine risk using a Bayesian statistical approach. This project is supported by drug regulatory bodies and has co-opted members of PVRI’s IDDI into its ‘International Group of Members’. Presentations followed on choice of risk scores from Hap Farber and use of composite end points from Christian Meier. Vibrant discussion ensued relating to choice of risk score in end points for both phase 2 and 3 trials, to be continued as a working group meeting with presentation at the PVRI Annual Meeting in Barcelona 2019.
The section on novel clinical trials, chaired by Jim White and Peter Fernandes discussed two topics:
- the length of a clinical study to gain meaningful results
- whether it would be possible to share placebo patients between different sponsors
The potential for interrogation of current large clinical trial data registries held by the pharma industry and by the regulatory bodies as an example of real world data was outlined by Peter. Further working group discussions are planned about the role of innovative trial design, including use of better stratification of patients at trial enrolment and enrichment strategies and about adaptive approaches to trial design and withdrawal studies.
Finally, the section on novel biomarkers, chaired by Lawrence Zisman and Anna Hemnes, explored this rapidly developing area. The challenges of both clinical trial design and novel surrogate endpoints in phase 2 studies of anti-proliferative approaches were discussed following a presentation from Janethe de Oliviera Pena.
The importance of ensuring that all three projects progressed at similar rates was emphasised, given their interdependence, and it was resolved that a single manuscript comprising three sections and a summary would be produced, responsibility for its delivery resting with the stream leaders.
The goal of the IDDI is to compile a position paper followed by a publication in Pulmonary Circulation, with all three workstreams presenting their work to the public.
The IDDI remains a vibrant exercise addressing much needed questions that must be solved before the future of trials comprising novel drugs will become possible, and importantly, has established a good rapport with regulatory bodies.