April 26, 2013 | By Márcio Barra
When planning a clinical trial, the question that the sponsor wishes to address is the starting point, and where the rest of the trial planning hangs. While the objective of the trial is often obvious to the investigator designing the trial, the question itself can be phrased poorly. Thus, writing a scientific, clear research question is a most valuable action when starting and establishing the study (1).
After coming up with a sound research question, the study design has to be elected. This choice is deeply connected with the desired information that the sponsor wishes to obtain regarding the drug product.
The appropriate selection of a study design is important, in order to provide scientifically-sound and unbiased information that answers the research question.
The best study design is the one that can answer the research question for that study, and different kinds of design are best suited for different questions.
A parallel design is the most commonly employed, followed by cross-over and the factorial design. The study design itself is linked to the intended statistical analysis. The study’s objective, nature of the study drug and the disease under investigation affect the choice of the adequate design, alongside patient selection criteria, randomization, blinding procedures (if any), choice of control and of course, current clinical practice and knowledge. More specific topics like the impact of drug-drug or drug-food interactions, impact of patient compliance and pharmacoeconomic outcomes can also be considered, depending on the development phase (2). Once these topics have been settled, the study design is translated into the research protocol (3),and the protocol writers can get into the minutia of the trial, like the dosage form, dose and the intended indication of the drug. The impact of the correct dose selecting for a trial cannot be overstated. Low dosages of the study drug may not produce a clinically significant effect, and the drug may be incorrectly deemed inefficient. High dosages on the other hand may cause deleterious effects (4, 5).
Choosing where to implement and conduct the study is a delicate matter. Based on the objectives of the company and market strategy for the drug, the company must pick where it makes sense to conduct its clinical trials (3).
Europe and the US are both valid choices, but more and more companies are choosing to conduct their large scale, pivotal trials in emerging economies countries, due to the ease in recruiting a large amount of patients – a big draw to pharma companies (6).
Aside from that, other points that a sponsor has to consider are issues related to drug access, cost, regulatory requirements and hurdles from different regions, applicability of data (results from a trial conducted in Japanese population might not translate well to a Caucasian population for example), contracting processes and the independent review boards / ethic committees for clinical trials. It’s important to stress the impact of fast approval times. Pharma companies place a lot of importance in countries that have a timely trial approval rate(7).
The last two noteworthy factors are the market potential of the country – is the country a significant player in the international economy and has he got a market that can afford the medication after approval? – and the quality of the execution of the trial versus the cost. Pharma companies want countries that recruit well and produce valid results at an affordable price.
After choosing the geographic location, the sponsor must identify and negotiate with competent clinical research sites in each location(3). The choice of which clinical trial site to conduct the clinical trial is very important, and pharma companies are very selective to whom they give their drug to be tested. The American Society of Clinical Oncology outlined seven attributes (8, 9) that make a clinical trial site exemplary, and thus a go-to choice for sponsors. These are:
1. Diversification of the clinical trial mix
A trial site should have the appropriate facilities and resources to offer a broad range of ongoing clinical trials for its patients, making the clinical trial site a very attractive proposition for sponsors. A diverse and successful trial portfolio, which took into consideration the available population and resources will bring companies from different research areas.
2. High recruitment rate
As previously stated, the patient recruit rate is the biggest factors that sponsors look into when choosing the clinical trial site, alongside approval times (7).Exemplary clinical trials sites should have at least 10% of the patients treated at the site participating in clinical trials. A high recruitment rate means that the trial activates new clinical trials in a timely manner.
3. Participation in the clinical trial development process
A trial site that promotes an active collaboration between its workers, an affiliated academic center and the sponsor of the trial is a huge plus for developing and implementing clinical trials.
4. Maintenance of high educational standards
The clinical investigation site must abide by high educational standards to all its employees working on clinical research. Continuous medical education, attending meetings conducted by trial sponsors, keeping up to date with scientific publications and attending meetings and symposia are all ways of meeting high educational standards. The presence of expert investigators and opinion leaders, who can carry a trial forward and help promote the knowledge produced in a trial can attract many sponsors (7).
5. Quality assurance
Quality assurance in a clinical trial site helps verify if the clinical research program of the site is performing at an ideal capacity and adhering to GCP guidelines and other regulatory standards. Quality control is the bread and butter of the pharmaceutical industry, and the industry likes to see that in their partners.
6.Multidisciplinary involvement in the clinical trial process
A clinical trial site that engages professionals of many disciplines will increase the strength of its research program. This increased breadth of knowledge and involvement will enable the site to offer more diverse and complex trials, thus attracting sponsors.
7.Clinical trial awareness programs
An awareness program aims to increase the knowledge about clinical trials in the site community. Promoting awareness engages the site stakeholders, increases the staff’s knowledge about clinical research and ultimately leads to the successful completion of clinical trials.
Focusing on these attributes will help a site develop well beyond the minimum Good Clinical Practice requirements, ultimately leading to a stronger research program. If the trial site is good, then sponsors will seek it to conduct their trials, simple as that.
In conclusion, the study design of a clinical trial is a complex project, where the research question is the starting point to a whole series of discussions regarding the study design. Various aspects influence the final study protocol, and after said document is complete, companies have to choose where to conduct the trial. Clinical trial sites that showed quality in their work in the past are the obvious choices for a company. Great care must be taken in these two steps so that the drug clinical research program goes as smoothly as possible.