View from 37,000 feet – weathering change in the Pharmaceutical Industry

Flying over the North Atlantic returning from a recent trip to India, I reflected on the evolution of the pharmaceutical industry in the United States over the past quarter century while anticipating years yet to come. Having encountered disappointing findings in a series of site audits directly linked to a lack of practical experience and knowledge of Good Clinical Practice (GCP), I was understandably concerned about the direction the pharmaceutical industry is taking. Outsourcing research to India, China, South America, Eastern Europe and other emerging areas has been growing at an ever-increasing rate as sponsors attempt to shorten development timelines and reduce costs. The challenge sponsors face is that such outsourcing adds a significant element of risk because the concepts embodied in international GCP are not yet well engrained in many emerging areas. This has been evident in my many trips to emerging areas as well as from my recent audits in India. While medical care in the trial was of high quality, the investigators and their staff had failed to follow GCP. As a result, five to six sites were disqualified and the sponsor lost over 100 subjects whose data could no longer be of use except for safety evaluation.

When one looks at the burgeoning pharmaceutical industry in India it is difficult not to draw direct parallels with the path we have been following in the US. Indian companies, especially CROs, are staffed by bright, well educated and dedicated people that lack the practical experience that comes with time. In my experience, upper management typically is highly skilled and experienced either through international or national pharma companies whereas the employees who perform most of the actual work are relatively new to the industry and possess little or no on-the-job experience. The element of having “been there – done that” is missing. India is not unique in this regard. Similar patterns have emerged as I have been traveling the world evaluating the quality of ongoing research programs.

During my 30 years in international drug development I have watched consolidation in the industry, driven by the bottom line, systematically gut companies of their ‘industrial memory’. What is left is a situation analogous to the pattern evident in the emerging world. In constantly striving to create more lean and mean organizations there has been a fundamental shift in drug development that no longer values experience. Timelines, often unrealistic and unachievable, are dictated by senior managers looking to pinch pennies rather than being reflective of the realities of the research process. As I work with companies to perform ‘gap analyses’, the shortcomings of management’s approach are clear. Management demands that more be accomplished in shorter time frames with fewer resources. Clinical research departments, being pushed beyond the limits of their staffing, capabilities, and knowledge base, are forced to contract out more of the research process that was formally done in-house by knowledgeable staff that has voluntarily or involuntarily departed. Predictably, CROs who step into the vacuum created by sponsor cost cutting often are staffed by individuals who were forced to leave sponsors as a result of cost cutting. Unfortunately, such experienced CRO personnel are no longer focused on a single sponsors study for any length of time, but are tasked with many other studies and duties.

The experience base has transitioned to the burgeoning service industries now supporting the pharmaceutical, biotech and device industries. Outsourcing research to CROs’ external consultants has become a fact of life. However, the pattern repeats itself. While the senior management of CROs may be experienced, after the CROs have been awarded a contract, they frequently assign the actual work to inexperienced junior personnel.

Outsourcing is not a new concept and can be effective. My great concern is regarding the oversight of those functions that have been outsourced. I often try to make management understand that you cannot ‘delegate and forget’ with the assumption that the CRO will deliver a good product in the end. Many sponsors that adopt such a philosophy have been severely burned as witnessed by the relatively high frequency of sponsors changing CROs.

Recently, I was asked by a venture group to evaluate a company they were financing to figure out why, despite a high cash burn rate, the company was behind schedule in most areas. Of particular concern was the lack of progress in clinical research. My analysis showed a similar pattern to that noted above. The company had bright, talented and motivated staff with limited experience that was expected to perform miracles with limited or no resources. Senior management had delegated responsibilities for the clinical program to a major CRO, and due to the lack of experienced personnel, the company failed to provide proper oversight. The CRO, without proper guidance and oversight from the company, had squandered enormous amounts of time and money without producing the desired results.

In another recent case, management of a company had pulled their contract from a major CRO due to poor performance. Management decided to go it alone without augmenting its staff with experienced personnel. The company aggressively selected vendors to support its research needs without properly vetting the vendors to ensure that such vendors had the capability, capacity and expertise to perform the required tasks. While management paid lip service to the QA process, they actually signed contracts prior to qualification audits being performed. The results were predictable. Well into the startup phase of the study, the company belatedly discovered that its vendors were failing to adequately perform and meet timelines. Upon closer inspection the vendors’ personnel assigned to the study were found to lack the expertise and experience to perform the required functions. Now the company faces program delays, remedial actions and additional expenditures.

It doesn’t have to be this way. Sponsors that have been through the CRO battles are adopting a new strategy. Instead of delegating all responsibilities to a large, full service CRO, they are opting to contract with smaller boutique CRO (“bCRO”) operations that have dedicated expertise in the specific areas required. Although it may increase the burden on a sponsor’s internal resources in the short term, experience has shown that the combination of experienced personnel within the bCRO and the integration of the bCRO operations with the sponsor’s research team pays huge dividends for both sides. Unlike large CROs, the bCROs maintain very experienced personnel on the job throughout the course of the study. Such personnel not only are more effective in executing the study, but they also provide a rich resource to train the sponsor’s staff. Moreover, the bCROs typically place greater value in each contract they receive resulting in a more focused effort on the sponsor’s behalf. In the end it is a win-win situation for both sides.

At Triligent we strive to achieve the goal of integrating with our sponsor’s teams at all levels. We have found that there are a number of key factors that lead to the success of any project, but perhaps most important is planning. The experience our staff has attained over many years in industry is provided to our clients in order to design programs that not only are timely and cost effective, but also achievable. We encourage companies to build in quality throughout their programs: Perform the due diligence audits up front; Qualify your vendors, investigators, labs, etc., before the study starts and continue the process yearly during the life of the program; Perform a GAP analysis to evaluate internal functions and capabilities early in the process and use the analysis to correct any areas of weakness before they become critical; When contracting with CROs or other vendors, choose wisely based upon qualification audits; Don’t delegate and forget – actively manage and control your contractors throughout the process.

When the clinical program starts, be aggressive and perform QA audits of your investigator sites very early in the process when the first few patients have been enrolled. In this way you can quickly identify and correct any issues that arise and thereafter disseminate the findings to all of your other sites to minimize the likelihood of problems being repeated and snowballing into a catastrophe. The experience I had in India that resulted in sites/patients being disqualified could have been avoided by conducting audits early rather than at the end of the study. Always keep QA in the loop. Properly utilized, QA can be a crucial ally for the clinical group and is key to the success of any program.

With careful planning and a renewed focus on quality, the future as viewed from 37,000 feet will be brighter and more productive.

Triligent is a boutique CRO that provides complete packages to aid sponsors manage their studies, including: Gap analyses of sponsors’ internal systems and staffing; Development of processes and standard operating procedures; Training of staff; Performance of qualification audits of vendors, CROs, investigator sites, etc.; and periodic auditing programs throughout the course of studies to be sure that client’s internal processes and staff, as well as outside vendors, are maintaining compliance with procedures, protocols, and applicable local, Federal and international rules, regulations and guidelines.