Clinical Trial Knowledge Missed, Gained, and Shared

In most industries, companies typically gather information and input from their consumers before initiating product development activity. With pharmaceutical development, this is not typically how consumer input guides the process.  

Historically, pharmaceutical and biotechnology companies have created development plans and designed protocols with little to no direct input

Ken Getz

from patients. Development sponsors have instead relied largely on publications and limited input from intermediaries-usually physicians and other health and research professionals-to define patient needs, endpoints and objectives, and clinically meaningful benefits.

In other industries, ongoing product development is also informed and refined by beta testing and soft launches. Here, too, active drug development programs receive input but it is limited by the requirements of the study protocol, principles of controlled clinical trials, and regulatory and ethical requirements. That input is also managed and interpreted by intermediaries-the principal investigator (PI) and study staff.

New research from the Tufts Center for the Study of Drug Development (Tufts CSDD) indicates that this process is inefficient and missing critical opportunities. Despite the depth and volume of data that is gathered during clinical trials, the interpretation and translation of knowledge and insights gained by the PI and study staff is not always reaching the sponsor. 

My colleague-Marie Smed, a consultant at the Technical University of Denmark-and I looked at the range of insights gathered during clinical research studies and observed inefficiencies and wide variability in the sharing of insights between sponsors and investigators into investigational drug product attributes and clinical practice considerations. And these inefficiencies were generally worse when a CRO was involved.

Identifying knowledge areas 

Based on extensive literature review and interviews with industry experts and representatives and healthcare practitioners, Tufts CSDD developed a list of primary areas where knowledge is gained about an investigational drug.  Eleven areas were identified across three broad domains:

Investigational drug attributes and effects

• Study drug side effects

• Study drug dosage levels 

• Concomitant drug interactions

• Study drug delivery form

• Risk/benefit of the study drug

Study drug administration 

• Administration of the study drug

• Clinical skills necessary for successful administration of the study drug

• Workforce required to administer study drug

Patient experience

• Cost-effectiveness of the study drug

• Patient access to the study drug

• Patient and professional reaction to study drug positioning (e.g., name)

Next, 451 global investigators (37% from Western and Eastern Europe; 28% from North America; 24% from South America; and 9% from Asia-Pacific) rated each of the 11 knowledge areas in terms of the level of insight that they obtain and their general ability to share these insights with sponsors and CROs during and after the conduct of the clinical trial.  

The results of this research showed that for half of the knowledge areas, a relatively high level of insight is gained and shared. But in eight of the 11 knowledge areas there was a significant difference between the level of knowledge and insight gained by the investigator and the level of knowledge and insight shared with the sponsor and CRO. PIs gain more knowledge and insight-in some cases substantially more-than they are able to transfer to the sponsor or CRO.  

Three of the knowledge areas-all associated with the patient experience domain-received the lowest ratings with respect to the level of insight obtained by investigators. They are not gaining much relative insight or knowledge into patient access and receptivity to product positioning. These areas are typically not central to clinical research study objectives. However, the insights gained from these knowledge areas inform patient choice and behavior.

Investigators indicated that the investigational drug attributes and effects domain contained the areas where the most knowledge was gained. And this knowledge was the most likely to be shared with research sponsors and CROs. Study drug side effects, dosage levels, concomitant drug interactions, and risk-benefit are among the areas most assessed during clinical trials as required by the study protocol.

Wide gaps existed between the level of insight gained about the administration of the study drug, the clinical skills necessary and workforce requirements to administer the study drug, and the level of insight shared with sponsors and CROs. 

Investigator ratings of knowledge shared with CROs followed a similar pattern to that reported of sponsors, but the level of knowledge shared was consistently lower.

Gaps and opportunities

PIs and study staff are obtaining a lot of knowledge about the study drug.  Some of this knowledge, particularly insights into investigational product attributes and their impact, is transferred well to research sponsors.  Knowledge transferred about study drug administration is less efficient. And knowledge about patient experience with the study drug is neither obtained nor transferred well.

The race to conduct and complete clinical trials may be playing part in limiting knowledge transfer. Study staff and their sponsor and CRO partners are frequently pressed for time as they must meet demanding timelines and as they are compelled to quickly focus on new projects once a given clinical study has ended.  

Clinical team focus on cycle time optimization and efficiency is likely detracting from opportunities to facilitate the transfer of important knowledge gained during study conduct. These operating conditions are even more pronounced when the CRO is involved. Contract service providers are primarily focusing on successfully executing the clinical study.

In addition, knowledge associated with patient experience and the adoption and administration of new medical treatments is typically less essential to the objectives of a given clinical

trial. Instead, emphasis is placed on answering drug-specific questions that primarily address safety and efficacy considerations. 

But in light of heightened focus on patient-centric drug development, perhaps more attention should be paid to these other knowledge areas. The principal investigator and coordinator are gaining-but failing to share-some insights that would better inform clinical practice and the treatment and care of patients. 

Should insights into patient access and experience with the study drug be encouraged and supported as part of the clinical trial process? Efforts to solicit patient, study staff, and healthcare provider input into study planning and design prior to finalizing the study protocol-via meetings, in-person, and crowd-sourced advisory panels-may be valuable ways to encourage and solicit this input.  

Product developers from other industries would no doubt be very surprised at the difficulty that the clinical research enterprise faces in trying to implement new approaches to amplify and respond to the voice of the consumer during the product development phase.  

Our ultimate consumer has a very important voice that must be heard. Soliciting insights from our patients is critical to not only designing more convenient and executable clinical trials, but also to delivering more relevant products and understanding and anticipating patient preferences and adoption. This knowledge and insight gained-and shared-is essential to engaging our patients and forming more lasting partnerships.

Kenneth A. Getz, MBA, is the Director of Sponsored Research at the Tufts CSDD and Chairman of CISCRP, both in Boston, MA, e-mail: kenneth.getz@tufts.edu