Every year, WCG Clinical asks a number of thought leaders about what they think is coming in their areas of expertise for the coming year. In a two-part piece that will be featured this week and next week, 10 subject matter experts from WCG and our partners share the important shifts, trends, regulations and priorities that will inform clinical trial development in 2020 and beyond.
The insights and predictions are grouped into six topics. They are: Scientific Advancements, Study Design and Study Conduct, Technology & Data, Public Policy & Regulatory Oversight, and Patient Advocacy. Below are the first five experts:
From my perspective, one of the most interesting things is that after all this time, we are still surprised by how hard it is to start and launch a new clinical trial. In addition to study complexity, it is often the first time the study team is assembled to work together. It is not surprising that the challenges of planning a complex project with people who have likely never worked together ends up being a series of unfortunate events.
One challenge that is a perennial favorite is adequate site selection. It shouldn’t be so difficult; it is quite straightforward on paper and yet, in reality, it is still astonishingly hard. On average, 11% of sites never enroll a patient. Original timelines end up doubling in order to meet the desired enrollment goals. When searching for a solution I think we should look to where we are succeeding in site selection. It is a mix of art and science; and a mix of technology and back-to-basics.
In no particular order, these are the attributes I have found, when done correctly, lead to more optimal outcomes and teams feel successful by achieving their intended milestones. Focusing on these attributes will be a priority for my site selection teams in 2020.
The role of independent sites in the conduct of clinical research continues to increase as a result of their ability to more predictably recruit patients from within their practices and/or through the databases they maintain, along with their ability to start up clinical trials faster and more efficiently than many academic medical centers (AMCs) and hospitals.
Independent sites can do this based on their size, agile processes they have in place and their reliance on focused patient engagement. From a sponsor and CRO perspective, there is a strong desire to work with those sites that can meet their enrollment commitments and have accelerated startup processes in order to meet the sponsor’s study timeline and budget.
In 2020 we can expect sponsors and CROs to continue to leverage the wealth of site performance data they have access to when evaluating and selecting which sites to include in their clinical trials. The ultimate goal in a given clinical trial is to identify the most appropriate sites that are focused on meeting or exceeding their enrollment commitments while meeting quality and ethical standards. This will allow sponsors to reduce the total number of sites that are required for a given trial. This means prospective sites will need to more accurately demonstrate their ability to not only meet enrollment commitments, but to also reduce startup timelines.
AMCs and hospitals who participate in clinical trials will need to streamline their internal processes for startup and enhance their effectiveness in patient recruitment. It is not uncommon for these larger institutions to take more than 90 days to complete startup activities, while independent sites can routinely do this in less than half that time. We can expect the AMCs and hospitals to more effectively leverage third-party organizations that can more adroitly execute critical activities like budget development, contract negotiations and patient recruitment. The reliance on third-party organizations that can partner with AMCs and hospitals to reduce startup timelines through their agile processes and enhance enrollment effectiveness through their proprietary processes and best practices will continue to increase. This is necessary as the competition for qualified U.S. sites continues to increase. This means institutions will need to be more open to modifying their current practices by partnering with providers who can not only augment their capabilities, but also make them more attractive to sponsors/CROs during the site selection process.
We can expect to see best practices embedded at the larger institutions in order to help them reduce startup timelines given the volume of patients that reside within their institutions and are under the care of their physicians.
In the next year, I expect that we will continue to see creativity, innovation and variety in the design of clinical trials — especially clinical trials supporting novel therapeutic agents and mechanisms.
Over the past few years, it has been increasingly obvious that the phase 1/phase 2/phase 3 development paradigm is becoming irrelevant to the way drugs are being developed now, especially in oncology; not surprising, since the basis of this framework was initially conceived more than 50 years ago by a statistician at the National Cancer Institute who proposed separating initial “drug-oriented” trials and later “patient-oriented” trials. New agents have been approved by regulatory agencies based on phase 1 clinical trials of more than a thousand patients, and early-stage studies with planned expansion cohorts to combine the assessment of initial safety and efficacy signals are now common.
“Master” protocols, including platform studies (looking at multiple agents which rotate through a protocol until either an efficacy or futility threshold is reached), umbrella trials (testing multiple agents for a single disease in sub-populations defined by genetic or histologic markers) and basket trials (“disease-agnostic” studies in which the population is defined by a genetic or histologic marker, regardless of the location of cancer or type of disease), are becoming increasingly common and increasingly complex.
Sponsors are avoiding the delay and administrative burden of study startup processes and looking for ways to move seamlessly from one development question to the next, without closing and reopening clinical sites and stopping and starting study recruitment. We are also seeing design innovation in the form of decentralized and “virtual” trial designs or design components, intended to reduce the barriers to study participation for patients (logistic, geographic, financial) and to increase the opportunity to participate in studies and the diversity of study populations.
These changes are positive and important, but they also bring challenges to the administrative and regulatory structures for the review, oversight and conduct of clinical trials, which are still based on the way studies were conceived and run decades ago. We’ll have to be innovative in these areas as well, to keep up with the necessary advances that are being driven by therapeutic innovation.
I predict substantial growth in the adoption of quality by design, risk-based quality management and centralized monitoring approaches detailed in the ICH-E6(R2) and ICH-E8(R1) addendums. During 2020, clinical studies that utilized risk-based approaches will be completed and inspected by regulatory authorities. Early adopters will be able to share lessons learned and reassure others that risk-based, data-driven approaches are both effective and accepted by regulators.
Two key factors will limit the rate of adoption: access to the data needed to support analytics and the availability of staff trained to interpret and act on the data. These challenges can be addressed through the adoption of industry-based performance and quality metric standards that improve the quality and consistency of the data available to data analytic programs. Additionally, risk management and root-cause analysis training programs — developed specifically for clinical research staff — can be deployed to reduce the workforce skills gap.
I believe that 2020 will be the year that the industry begins to realize the benefits of risk-based quality management and centralized monitoring — namely, using data to identify when human intervention is required to investigate whether patient safety and/or data integrity issues are occurring and take rapid action before they impact the integrity of the research.
In 2020 I see the research ethics field’s struggles with data security and data privacy escalating.
While there has been a longstanding recognition of privacy issues around medical records — and regulations like HIPAA to protect that information — there is an ever-growing amount of personal data that is being converted for research use. From social media to Google searches, browsing Netflix and shopping on Amazon, we each contribute a vast amount of data about ourselves to various entities. Everyone with a smartphone, smartwatch or wearable fitness device also contributes data about ourselves to the companies that make those devices. There is a wealth of research being done using these devices for medical purposes, such as the diagnosis of medical conditions and mobile apps to improve mental health. However, there is also research that is less obvious to the public and fewer controls to protect the privacy of that data. When some of this research is revealed to the public, such as the Facebook emotional contagion study or the research done by Cambridge Analytica, members of the public often express outrage and surprise that their data is being used in this manner, even when they agreed to such use at the time they signed up for the service.
Outside of research there have been numerous data breaches in which personal financial information was stolen. If there is a data security event tied to the research use of data, it could have a significant impact on the public’s perception of research uses of their data.
While research uses may be consistent with the terms of service or end-user license agreements that individuals agree to when activating a device or setting up a social media account, most members of the public are unlikely to have given any thought to potential research use. It may not happen in 2020, but the chances of a research-related data breach are only going to increase. I’ll be watching to see if there are any significant new developments in this area.