Effective planning and conducting clinical trials in rare diseasesDate:02 February 2017
Six to eight percent of the European population suffer from a rare disease which is roughly equivalent to 27-36 million citizens. In addition to the approximately 7000 known rare diseases about five new such syndromes per week are described in the literature. Till 2018 the global market for the treatment of rare diseases is growing at an annual rate of 7.4% to a total of 127 billion$. Despite these impressive figures, the medications in development must still master the hurdles to approval. This requires special skills in effective planning and conducting of clinical trials.
As the term “rare disease” already indicates, the number of eligible patients is very low - often only a few per country. Therefore, the costs per patient are very high, while the total cost of the study is generally lower as in conventional projects. Due to the small number of cases every patient early dropped out or any delay in the approval process causes significantly higher costs than in larger projects. In addition to the financial constraints, there might result a damage in reputation regarding affected patient organizations and their supervising physicians. This could be more distinct as for conventional projects.
Planning phase is gaining importance
To realize cost advantages against conventional projects, it is advisable to invest more effort in the planning phase. A predictive planning helps to use the resources, both man power and material, efficiently and to terminate the study simultaneously across participating countries / centers.
In parallel to the creation of the protocol design, it should be worked on strategy and risk planning. However, a straightforward cost planning is not useful without consideration of possible risks.These include the necessary and timely contact with authorities, planning of reimbursement discussions, patient care (for example home-care), early conversations with study participants and patient organizations as well as market access considerations ("evidence-based marketing") and measures to "patient retention".
Potential risks must be recorded, financial implications should be mapped and appropriate measures taken on occurrence.
The possibility to expand or stop a project at an early stage geographically, temporally or in terms of cases should be considered and hence captured financially. Also be aware that in many, often emerging markets, after the end of the clinical projects until market authorization the participating patients expect the medication provided free of charge. This may impose considerable additional costs.
The strategic plan needs to be implemented in the operational procedure. Thus, also the suppliers (CRO) profit from personnel with a comprehensive understanding of the process. In contrast to projects that include many patients, rare disease clinical trials require customized processes and additional services. Changes in staff are more difficult to compensate compared to conventional projects. Project management and clinical monitoring demand other priorities and more extensive responsibilities.
In the project business quality and the handling of potential risks can be planned properly. Often, this is not yet considered sufficiently. The reasons for disregarding this important instrument of control are complex. One reason is the frequent demand of early first patient inclusion and misplaced priorities at milestone-related payments. Repeatedly a lot of money is invested, to completely rule out a tiny residual risk - money that would be better invested otherwise ("zero-risk bias"). It is advisable to include the selected CROs in the planning activities at an early stage and to whip up on the common objective to control risks and to master processes at any time.
Due to the funding of research projects on rare diseases, the interest in this area has suddenly increased. Not only for biotech companies but also undoubtedly for the benefit of the affected patients.
The special requirements for the clinical development of "orphan drugs" can only partially be met with traditional thinking.
Therefore, besides the adjustment of in-house personnel structures the choice of suitable suppliers - of CRO -may not only help reduce costs, but in extreme cases, may mean the difference between success and failure of "orphan drug" development.