Guest Commentary: Quality in Clinical Research --- An Indian Perspective
At a recent ACRP chapter meeting in India, industry leaders participated in a panel discussion on quality in clinical research in India. The panelists included: Larisa Nagra Singh, senior director, Asia Pacific ,ICON; Dr. Sacchidananda, dermatologist, registrar evaluation, Rajiv Gandhi University of Health Sciences, Bangalore; Suresh Ramu, vice president, Quintiles; Mitesh Patel, head, CTL Services, Quintiles India and director, clinical operations, Bangalore; and Dr. Anil Shinde, clinical operations, director, NovoNordisk. The discussion was moderated by Dr. Raman Shetty, director clinical research, Allergan, India. The following is an excerpt from that discussion prepared by Dr. Shetty of Allergan and Pratibha Nadig, M.D.; Medha Joshi, M.D.; and Santosh Hegde (all of the Bilcare Research Academy, Bangalore, India) .
Clinical Trials in India have increased exponentially in number over the last decade. The increased business has brought into sharp focus the need to manage quality while conducting clinical trials.
Several audits and inspections by health authorities have reaffirmed the fact that good quality is possible while performing studies in India. Clinical research is a dynamic and constantly evolving field and quality standards need to keep pace with the evolving standards and new tools being developed. Quality in clinical research needs to be rigorously maintained by all the stakeholders of the clinical trial process. This includes the ethics committees, investigators and sponsors alike. At this stage of high growth, it is critical that all clinical research practitioners in India deliver consistent, efficient and quality clinical research across the board.
A panel discussion was organized to debate issues related to quality while conducting studies in India from the perspective of a site, the sponsor and a CRO. The discussion also focused on the unique challenges faced in India while implementing quality management systems. During the discussions, panellists provided suggestions for benchmarking the standards for quality and laying a road map for each stakeholder to achieve the standards established.
The following is a detailed report of the panel discussion held as a part of the 3rd meeting of ACRP Bilcare Research Academy, Bangalore, on 13th Dec 2008.
Challenges in Improving Quality in Clinical Research: An Indian Perspective
Raman Shetty (RS); Dr. Sacchidananda (SC); Suresh Ramu (SR); Anil Shinde (AS); Larisa Singh (LR); Mitesh Patel (MP)
RS: Is there a problem about the quality of data being generated by India? What are the top 3 challenges faced by you while enforcing global quality standards in your studies in India?
SC: The key challenge is in getting the right people. In my opinion, it helps if the study coordinator is a medically qualified person as he is aware of what is being documented. This greatly reduces errors in the source data. Another challenge lies in making the site coordinators document events accurately. While mistakes do happen, it is all right as long as there is a documented reason for any discrepancy observed.
MP: There is no problem in the quality of data generated from clinical trials conducted in India as such. However, one cannot deny that there are sporadic cases that cause concerns about the quality of clinical research in India. Quality variations do depend on the therapeutic areas, as well. For example, certain conditions like psychiatric illness may pose a challenge for the data quality due to subjectivity involved with the patient assessment and use of multiple scales. The other challenges seem to be the maturity levels of the clinical research professionals and the resource constraints in that professionals have fast-tracked careers without allowing time to consolidate themselves in the respective positions before moving on to higher roles.
LS: The challenge ahead lies in understanding the process of clinical research, interpretation of guidelines, training and experience of the staff members. Clinical research professionals should have a complete picture of the process and understand the criticality of their role. They need to be intelligent monitors who can observe patterns and trends rather than blindly following procedures. Monitors need to be strong and capable of taking clear and objective decisions and also be detectives of high calibre.
AS: There are some lacunae in methods of practices in India. The medical records in some of the hospitals are not adequately stored due to which the existence of patients can become questionable. Also, it is a fact that many of the sites lack good documentation practices. A high turn-over of clinical trial projects in some of the sites is also a factor that is affecting the quality.
SR: The problem of delivering consistent high quality in clinical research is not only in developing countries like India but also in the western countries. It is not the region where the trial is done but the attitude of people that matters. The challenge ahead is to inculcate an attitude of quality among the professionals. Professionals should be trained to understand the socioeconomic and regulatory implications of poor quality data. We need to organize educational programmes to build up awareness in these aspects.
RS: The boom in the CR industry has had a few negative fall outs; among them is high attrition, unreasonable employee expectations, companies being forced to accelerate career progression, etc. This has lead to people with relative inexperience handling positions of high responsibility compared to their western counterparts. Could this impact the quality, and if so, what best practices do you adopt to tackle this?
LS: The impact is certainly there; people now expect faster growth in shorter time. It is sometimes necessary for the company to give higher responsibilities and promote people earlier than the expected period. Such situations require a high degree of management supervision. Companies should discourage this practice. Of late, professionals appear to be eager and expect fast-track career growth but, in the bargain, tend to lose out on the learning process. I would suggest young professionals to enjoy their experience and learn as they progress in their career. Expectation of accelerated growth with a fat package will hamper learning and, in turn, affect performance and quality of work. These issues need to be addressed as a part of their training in clinical research.
RS: Data management is a relatively more controlled environment with well defined processes covering each task. The amount of patient data to the global pool being contributed by Indian Data management (DM) teams is higher than that of Indian clinical teams. What quality metrics do you use to handle these massive numbers of transactions and a very large pool of personnel (some with very limited skill sets) involved? Are there any practices currently being used by DM teams that could be adopted by clinical teams?
SR: If one can look into the statistics, India is involved in managing 15 to 20% of the global data management activity. Out of this, 1.5% data is of Indian origin. We estimate that about 3,500 professionals are working in this area in India. Quality of the work done from India therefore assumes high importance. I would like to categorize quality under two headings: 1) absolute quality that qualify the process quality measures at the end of the process, and 2) relative quality that is said to meet the quality requirements if it meets the expectations of the customer. Accountability, accuracy and integrity are essential data quality parameters. We observe the quality trend, i.e., the error rates over a period of time, that will help us in implementing corrective measures. ISO and six sigma concepts have helped in the quality control measures globally. Measures of control also need an emphasis on the assessment of working professionals for their attitude towards and competency in adhering to the quality parameters.
RS: Hospitals in India are typically designed for dealing with large patient volumes and clinicians are encouraged to treat the highest number of patients in the shortest possible time. How does a PI manage his research commitments in such an environment without compromising on quality?
SC: This is possible by engaging, as I said earlier, professionals who are well qualified and understand the process well. We need to build a separate team in the department that focuses only on clinical trials. In addition, the investigator and his team must develop the art of multitasking. Most importantly, good training will ensure good documentation helping the site meet quality standards.
RS: Studies in India typically start later than centers in the West and quickly exceed their original recruitment targets in a very short time. This often strains the available resources and could potentially impact the quality. What strategies do you use to tackle this?
AS: The most important factor to get the studies done at a faster rate is the proper site selection. Moreover, our experience says that the presence of a CRA at the time of first patient recruitment is critical to make the site team understand the process thoroughly as per the sponsor's requirement. Frequent meetings and regular intense training is equally important. Assistance should be provided to the trial staff as and when required. For less experienced sites, it is always better if a project manager accompanies the CRA during site visits.
RS: You have worked overseas for an extensive length of time and also in India. In your view, is there a difference in the way Indians perceive quality as compared to our Western counterparts?
MP: I do not think there is a difference in perception of quality per se. Though not necessarily correct, our western counterparts certainly have a perception of lower quality in India and the good news is that this perception is changing. In the West, professionals are more mature in doing the trials. In India, professionals are very committed to doing a good job and that compensates for the lack of years of experience in this field. Sometimes, in the process of being innovative, our professionals tend not to follow rules strictly and that could potentially threaten quality. As such, the CRAs and other research professionals may be under peer pressure for moving on in their careers a bit prematurely and that could also have an impact on the quality of the deliverables. Also, some investigators take up the clinical trial management as just another assignment. In such cases, the CRAs should be more diligent in ensuring that the investigator is able to allocate enough time to doing the trial and provide adequate oversight to the study personnel for smooth execution of the trial. Lastly, we need to set up quality checks at each stage of the trial and conduct periodic audits based on the pre-identified triggers.
RS: Are there any pre-conceived notions on quality among our global counterparts when planning a study in India? How do you manage this and what steps do you take to address their anxieties?
AS: There are definitely some pre-conceived notions about quality among our international colleagues. But this is quite easily addressed by arranging visits to sites, making them understand how the system functions in India and communicating continuously.
RS: Companies are aggressively moving to a paperless platform and clinical trial management systems for their studies. Has this impacted quality negatively or positively? And to a larger question, when organizations transition to new technologies or standards, what steps do you take to ensure that there is consistency in the quality of operations during this transition?
SR: Deploying technology solutions allows the data to be viewed from different angles and certainly can help improve the overall data quality standards and patient safety. It is usually assumed that these technology solutions simplify the ability integrate the data across disparate sources, and hence that the data quality will automatically improve. However, in fact, the implementation requires the adoption of standards across different data sources and across trials to reap the real benefit of data integration. It also takes time for the people to adopt new technologies. Very often at clinical trial sites, it is seen that data is entered on paper and then transferred to an electronic system later resulting in delays and possibly data quality issues. We need to move to getting the data right the first time around.
LS: I would just like to add that solid training is again essential for EDC studies and it is very important to do this at the site level, too, since the systems are very precise and SOPs need to be stringently followed.
RS: FDA inspections have been very few in India over the past 10 years but this is expected to increase exponentially over the next few years. As one of the handful of PIs in India to have been inspected by the U.S. FDA, what tips would you like to share with other PIs and clinical research professionals in India who would not have had this experience?
SC: My suggestions would be to be realistic and transparent. We need to give an accurate picture to the auditors and do not attempt to cover up. Competitive enrollment can often be detrimental to the quality at the site as the site is then more focused on the recruitment than the quality. Further, the site needs to maintain very accurate source data. Think before you commit anything to paper and ensure that no coercion is used on any patient to make them participate in the trial.
RS: Final words on qualify for a young CR professional entering into the industry?
SR: Quality starts and ends with each one of us.
AS: Be a friend and also a policeman; focus on training.
LS: Discipline and quality go together, keep learning and growing.
MP: Be passionate about what you do, be politely assertive; you are the guardians and gatekeepers of quality in clinical research.
SC: My colleagues have said everything, and I don't have anything further to add.