Applied Clinical Trials
The current regulatory environment of a particular country plays an important role in the geographic selection. For India, it is very relevant because of problems in clinical trials approval and conduct issues during last few years.
In developing a clinical trial program, the need to include global sites is necessary, as are the subsequent study feasibility tasks. The current regulatory environment of a particular country plays an important role in the geographic selection. For India, it is very relevant because of problems in clinical trials approval and conduct issues during last few years. However, there have been some changes made to that country’s trial review process to make it more streamlined, which is allowing quicker trial approvals.
This article will highlight our experience performing study feasibilities in India. A detailed feasibility study is critical for the planning and conducting of successful large-scale global clinical trials. Increasingly, study sponsors and contract research organizations (CROs) are recognizing the value of performing a comprehensive feasibility assessment in mitigating risks involved with a clinical trial.
A feasibility study helps to promote better trial design and study execution, thus ensuring that trials avoid unnecessary delays by identifying the potential investigator, meeting their planned schedules and patient recruitment targets.
When performed well, sponsors and CROs have found that a feasibility study is invaluable in contributing to the success of a clinical trial and produces many significant benefits when finding that just-right clinical site. Poor site selection can be considered a key reason of clinical trials completed late; and eventually become costly in terms of resource and time allocation.
In global feasibility, India has many benefits. The country has a large population, with high numbers of patients with many diseases such as hypertension, diabetes, cardiovascular disease, as well as many types of cancers and rare diseases. Additionally, many patients are treatment naïve or newly identified. These facts release the main pressure of patient recruitment, where the only effort left is to find the right site.
The main attributes for India also include 2,000 GCP-trained investigators, who have conducted structured research. More and more sites, including medical institutes and hospitals, have strengthened their policies to accept research proposals. There are increasing numbers of trained clinical research professionals contributing to the development of this industry and growing clinical research environment.
Conducting a successful feasibility study
Many times, pharmaceutical sponsors look to use the expertise of CROs in conducting the initial feasibility for their project at global level. In our experience, when sponsors perform feasibility on their own, there can be a high possibility of potential bias with the particular site. There can be a persuasion from the other cross-functioning departments, such as marketing, who are in direct contact with a particular investigator.
CROs can help provide those unbiased and objective feasibility assessments ranging from exploratory country specific data relevant to the therapeutic area through to detailed protocol and site information.
We recommend a dedicated team of persons from different backgrounds and expertise are involved in planning and conducting a detailed feasibility study. The first prerequisite of such a team is the detail understanding of the particular therapeutic area, disease modality, available epidemiological data and information related to ongoing competitive studies in a country or region. It can be beneficial to include experienced managers from project management, clinical monitoring and medical affairs who can underpin both unrivalled feasibility and operational risk assessments.
In general, feasibility starts with the review of protocol in consultation with medical experts; and they would be able to check if the proposed study is rational-scientifically as well as ethically. The core idea of the study design and the related requirement should be propagated to the feasibility team. The operations team, then, would be able to gather those challenges, sort out possible solutions. The regulatory team is responsible for identifying the regulatory aspects. This would help to decide the scope and extent of the feasibility study and design a step wise process and documents to carry out the task.
Tools and Tactics
It is advisable to have a database or a repository of clinical investigators, which can help to shortlist few potential investigators. Here the past performance of the site and track record must be examined, if available. The sites must be differentiated on the need basis, and one must be careful in selecting the site that has representation of a Key Opinion Leader (KOL) in a particular therapeutic area, and also have stringent research policy e.g., major academic institutes. Before short listing a renowned KOL for the study, his or her time and interest must be evaluated. Although investigators can claim to recruit high numbers, the investigator’s capacity to perform the trial with the available resources and staff must be weighted.
An initial phone discussion is the first and simplest way to get in touch with the investigators to ask them the right questions related to study. This conversation can be a good point to check for the investigator’s interest, as well as provide further information.
In most of the cases, investigators are too busy to answer every specific details over the phone, although, a short discussion can be a source of valuable information. This certainly helps having an establish rapport, when there is a paucity of time. This initial discussion with the investigator can provide vital information on the possibility of conducting the study at sites. It can also serve as a quick epidemiological survey, which can give better approximation on subject accruals.
The most important tool for the feasibility is a well-designed Feasibility Questioner Form (FQF). A FQF is an assessment of clinical trial site’s potential for patient recruitment. Sites are sent a brief protocol synopsis of the proposed trial and requested to answer various questions relating to the site’s clinical trial experience, its facilities, previous experience with recruiting for a particular therapeutic area, and its ability to access the required patient population. Based on these feasibilities, sites are chosen to participate in the proposed trial.
An investigator’s team should be provided with the basic information in order to have an overall requirement of the study. FQF itself should be able to provide sufficient information about the study and the requirements to get realistic data about the site’s capability.
Following essential information should be provided:
The feasibility response will help to differentiate a site for an actual site selection visit. The response must be thoroughly assessed in order to comprehend and devise the true picture of the site, to assess the patient population and estimation of enrolment based on the inclusion and exclusion criteria. One should also check the staff availability, ethics committee details and site infrastructure. It can serve as a comprehensive validation tool.
Another rule of thumb in feasibility is to generally select 60%-70% of sites with whom the CRO/sponsor team should have prior working experience. One of the most important aspects is the professional working relationships with such investigators that will help to get faster and clear responses.
There are cases, where it was imperative to identify new sites in a new geographical area, depending on the expertise of investigators. These investigators, when selected and adequate training is provided, can perform very well.
A Success story of Gastroenterology study feasibility
There is a wide variation in the prevalence of the peptic ulcer disease in India. One sponsor wanted to perform the clinical trial for their established generic drug for active Duodenal Ulcer as a monotherapy. The preliminary discussion with Indian gastroenterologists concluded that due to availability of the better drugs and formulations, the majority of clinicians were reluctant to use it as a monotherapy.
Having many negative responses from the senior clinicians, the entire team was challenged to dig deeper into the reasons for it. The feasibility team modified the questionnaire based on the responses received from the investigators and regulatory guidelines, mainly related to the size of the ulcer. It means, based on the pathology of disease, the entire focus was made on the patient population having a specific size of ulcer, which can be considered for the study. The team decided to do the thorough discussion with prospective investigators, based on the new insights. Ultimately, the team was successful by not only getting accurate information from investigators on estimation of patients, but also convincing them about their participation in the study. Most of them have agreed to enroll the required number of patients in stipulated time.
This example can substantiate how important it is to combine practical insights with the scientific information in a clinical trial.
In clinical trials, the recruitment of right patient at right time is the most important factor for success. The selection of investigators to meet this objective can be difficult at times. Performing a thorough feasibility provides benefits throughout the course of the clinical research program. It can be inferred that feasibility is not just a ‘nice to have’ process, but an essential step to climb the ladder of project success. India, as a country with a large population, experienced number of clinical investigators, and their preference about particular class of drug/molecule also varies. This enables sponsors to have a variety of options available for their feasibility in particular area. Hence, including India as part of the global clinical trials to achieve the timelines and better quality outcomes is helpful.
Fig. 1: A general approach of performing the study feasibility.
Mr. Purav Trivedi, RPh, MSc, CCRA, is Clinical Team Leader at Cliantha Research Ltd, India. Dr. Chirag Shah, PhD, PGDPM, is Head and General Manager – Clinical Trials, Cliantha Research Ltd, Ahmedabad, India. His email: CShah@ClianthaTrials.com