April 27, 2013 | By Márcio Barra
The clinical development plan is a complex document that entails the entire clinical research strategy of a drug, describing the clinical studies that will be carried out for a pharmaceutical entity, created by a pharmaceutical company. The CDP is founded on the information of the Target product Profile (TPP), which states the goals for the drug product, estimates the net value and forms the basis for the go/ no go criteria. The CDP presents how will the pharmaceutical company reach the criteria stated in the TPP (1, 2).
The plan itself is absolutely crucial to the success and unbiased assessment of a potential pharmaceutical entity. Clinical trial projects are typically extensive, complex and expensive endeavors, and the CDP’s elements help by setting up beforehand what will the company plans to do in order to (3, 4):
- Successfully complete the pre-clinical and clinical research project of a drug and establish the efficacy and safety of a drug for use in humans, in a dose range and schedule that provides an acceptable risk /benefit relationship.
- Estimate the budget of the project.
- Attain approval from a regulatory authority and bring the product to the market.
For a successful CDP, the company must define a product profile of pharmaceutical entity before any clinical development, which includes (3-5):
– The identification of the desired indications and the potential label claims of the drug product. This is the focus of the research program.
– A thorough description of the drug product, including the routes of administration.
– Definition of the target population.
– Analysis of the market; where the competition stands and what drugs do they have in the pipeline. If a drug with no defining characteristics is expected to enter in a crowded market, it may not even be worth creating a CDP.
– Finding research development plans that were used for similar products if possible, and check available guidance’s. Reviews and approval documents of similar drugs from both EMA and the FDA can also provide useful information, as well as FDA advisory committee transcripts
– Defining the regulatory strategy of the product. Will the drug follow the normal regulatory pathway, or is it eligible for orphan drug status? And will the company request scientific advice from EMA/ FDA?
These components set the goals and objectives for the clinical development program of a drug substance. The main elements which the CDP then explains and elaborates upon are (3-5):
- Background pharmacology, scientific summary and rationale of the drug – What is known about the drug product, like its PK, PD, mechanism of action and expected side effects. The target population of the drug is also detailed, forming the basis of the clinical studies.
- Clinical studies planning – The planning of the clinical studies is the core of the CDP, as it’s the pathway through which the drug’s properties will be assessed, like its ADME, activity in the target receptor, benefits and risks, and attain Proof of Safety (PoS) and Proof of Mechanism (PoM). The CDP must present the general outline for each clinical trial planned for the drug, from Phase I to Phase III, and Phase IIIb and IV if applicable. Different study phases serve different purposes, and the clinical outcomes for each study must be identified. Besides the outline, the CDP should also present a time frame for the studies – typically presented in a Gantt chart.The success criteria of each study are defined as well, taking into account the acceptance criteria written on the Target Product Profile.
- It is also common, in cases where a company doesn’t have enough funds to carry on with the entire clinical investigation procedure, that the CDP of a drug only details proof – of – concept studies, in order to attract investors and venture capital to fund the rest of the clinical investigation. This might change according to the strategy of the company.
- More specific studies that might be warranted depending on the drug, like Drug – drug interaction studies, organ impairment studies, special population studies, and others are also described.
- Schedule of the deadlines for milestones and decision making –These are the Go/ no-go decision points, where a company might, for example, have to evaluate if the risk/benefit ratio attained in a study is acceptable to warrant further research and obtain market approval, or if the project should just be dropped altogether.
- Development costs – What is the expected budget for the clinical research program of the drug. This estimation allows the company to plan and adapt its resources and strategy accordingly.
- Identification of potential issues and bottlenecks in the development process – The sooner these are identified, the better a company can prepare to deal with them.
- Regulatory and market strategy for the product – When will the company approach the regulatory authorities for advice and approval, and in what markets will the company attempt to launch the product. Different markets might warrant specific studies, as different populations might require a study targeted to their genetic characteristics or food habits for example.
In summary, the CDP is an essential tool to successfully bring a novel drug product to the market. It details how the company will work on the “vision” laid out on the TPP, creating a solid foundation for the coming clinical trial protocols.