Sponsor companies and service providers have embraced more strategic management of their clinical supplies while regulatory pressures and the volume of global clinical trial activity have increased. Pressures to achieve shorter study start-up timelines and enroll larger numbers of globally dispersed study subjects have made clinical supply management even more complex. Downstream, investigative sites face numerous challenges including delays in receiving supplies; managing disparate supply deliveries; dealing with multiple vendors; labeling issues; and temperature excursions. 

Current study planning and practice relies heavily on the use of interactive web or voice response technology (or interactive response technology), also referred to as IWR or IRT. These tools are often integral to investigative site management of clinical supplies.

  At minimum, IRT systems help to reduce site burden and expedite reconciliation and return of unused investigational product (IP) at the end of a study.

  Published data indicate that IRT for clinical supply management will increasingly play a major role in managing global trials.

  Improved IRT systems could allow for better support overall for timing of supply and re-supply, mitigating issues such as limited storage space available at the sites and support proper labeling. IRT can also be used to manage patient compliance issues with the use of mobile patient visit and medication reminders.

Despite the large investment and major role that IRT plays in helping sites manage global clinical supply, there is little published data on IRT usage and its impact at the site level. Indeed, to our knowledge, investigative site experiences with, and perceptions of, clinical supplies have received scarce attention. Such a perspective would be invaluable to sponsors and contract research organizations (CROs) in identifying opportunities to improve study conduct collaborative effectiveness and efficiency. 

To address this need, Tufts CSDD recently completed a study among several hundred investigative sites around the world to gauge their capabilities and experiences with clinical supplies. 

Tufts CSDD, in collaboration with seven major pharmaceutical companies and CROs, developed an online survey for global site staff directly involved in managing clinical supplies. The survey was designed specifically for the role of study coordinators, investigators and sub-investigators, pharmacists, technicians, and Qualified Persons (QPs). An online survey was comprised of both multiple choice and open-ended questions. An invitation to complete the survey containing the survey link was distributed to Tufts CSDD contacts and mailing lists by e-mail during May and June 2013. Responses were anonymous and confidential and were reported only in aggregate form. 

The survey examined three broad areas: site capabilities in handling clinical supplies, assessments of sponsor and contract research organization (CRO) abilities to handle clinical supply responsibilities, and key areas of opportunity and challenge. Approximately 4,500 emails were sent out to unique sites globally and 304 surveys were completed yielding a 7% response rate. 

Overall respondents were primarily investigators (46%) or study coordinators (41%) while 13% were pharmacists. Respondents were distributed globally with 39% based in North America, 20% based in Latin America, and 30% based in Eastern and Western Europe. Sites conducted a median of nine trials per year across a wide range of therapeutic areas; the top therapeutic areas included cardiovascular trials (19%); central nervous system (17%); metabolic/endocrine (14%); and oncology clinical trials (8%). 

Respondents conducted trials in a number of settings: one-third (31%) are in government/hospital settings, 36% are in academic medical centers, and 43% are in for-profit independent sites or site networks. Most sites reported using a central pharmacy (62%), while the rest used an in-house pharmacy or an outsourced pharmacy (9%) On average, there were 4.24 full-time equivalents dedicated to managing supplies and 2.91 part-time equivalents. 

Overall, respondents perceive that they are generally well prepared to handle clinical trial drug supplies. There were a few exceptions: more than half of sites (54%) reported that the amount of space available at their center was "very adequate."  In a separate free-text question, nearly three-fourths (74%) of 103 mentioned that they have limited storage space available on site. 

Sites also indicate that they have limited abilities to handle novel therapies such as gene therapies or personalized immunotherapies. The highest proportion of sites said that they are able to handle vaccines (42%), blood and blood products (41%), and therapies with companion diagnostics (32%) (see Figure 1). 

Site assessment of sponsor and CRO performance

In general, the majority of investigative sites rate sponsor/CRO clinical supply responsibilities positively. Clinical supply availability, responsiveness to inquiries, and the quality of training are among the areas receiving top ratings. Respondents also indicate that sponsors and CROs perform well with respect to receipt and acknowledgement of drugs and supplies and documentation clarity (see Figure 2). 

Throughout the survey, a relatively low proportion of sites rated sponsor and CRO performance as "Excellent," indicating widespread opportunities to improve. Investigative site responses—both closed- and open-ended—also reveal a number of areas where there are major opportunities for improvement: 					

Unexpected amount and arrival time of supplies

Seventeen percent of respondents rated IRT "Poor" and "Fair" with respect to design, and 13%  gave a low rating to IRT ease of use. More than one-out-of-four sites rated the number of IVR steps to get a drug dispensed as "Poor" to "Fair." 

Another issue examined across sites was the frequency with which delays prevented dosing of first patient. Sites conducting trials in oncology, infectious disease, respiratory, and hematology were more likely to report delays preventing dosing of first patient than those in other therapeutic areas. 

The most critical challenge in receiving supplies was having supplies arrive unexpectedly at a site. Nearly four out of 10 sites report significant challenges with receiving supplies at unanticipated times (see Figure 3). Other notable issues were having unexpected amount of drug, bulky packaging, and insufficient communication about receiving drugs or supplies. Other difficulties mentioned were logs that needed to be completed manually rather than in an automated fashion, ensuring proper security for drugs and supplies, and the need for proper instructions in handling drug. 

Label design or formatting was also viewed as challenging. Some of the most frequently mentioned labeling challenges reported were difficulty in reading the kit number or label text and not enough room to write on the label. 

			Respondents reported challenges in the area of temperature-monitored supplies specifically with temperature excursions and dealing with defective or complicated equipment. Our analyses revealed further differences by therapeutic area. Sites conducting trials in oncology, infectious disease, respiratory, or hematology therapeutic areas were more likely to report challenges with temperature excursions than those conducting trials in other areas. This difference was statistically significant (p <.01). This finding is not surprising given that sites participating in research with temperature monitored products (e.g., oncology and hematology) are likely to report challenges with temperature excursions. 

Another challenge to site staff is patient compliance. Respondents estimate that nearly one-quarter of patients experienced a compliance issue in 2012. Our analysis by site volume and region suggests that sites conducting a greater volume of trials per year experienced more issues with patient compliance than those conducting fewer trials per year, and those sites in the rest of world report more patient compliance issues than those sites based in North America and Western Europe. These differences were statistically significant (p=0006; p <.0001). Some of the issues contributing to patient compliance were sponsor or site specific, including poor labeling or instructions, including small font size, readability of labels, and use of booklet labels. Other issues included large or complicated packaging, side effects, and the length of a study. The last category of challenges was patient specific, such as lack of reminders or patient forgetting and patient education. 			

Overall, sponsor and CRO clinical supply practices receive a good first report card and this will serve as a baseline to measure against in the future. Sites indicate that in general they were satisfied with the availability of drug at their sites and rated most sponsor practices favorably.  Top improvement areas include complicated IVRS processes; unexpected amount and arrival time of supplies; cumbersome delivery and return packaging; and defective equipment. 

Differences in perceptions were observed across respondent subgroups, including study conduct setting, geographic region, and clinical trial volume. These differences suggest opportunities for targeted areas of improvement. Future Tufts CSDD studies will explore these differences in more detail. In an upcoming study, Tufts CSDD will also be examining the impact of logistical factors, such as the role of cold chain handling, requirements for temperature and time zones, storage and distribution, regulatory, and customs within the management of the global supply chain. 

Clinical supply challenges were particularly evident in specific therapeutic areas: oncology, infectious disease, respiratory, and hematology. Increasingly, trials conducted in these therapeutic areas utilize temperature-controlled drugs and supplies and the costs involved in shipping and transporting clinical supplies are high and may require that current sponsor-site practices be re-assessed or evaluated. As more sites deal with temperature-controlled products and moving those through temperature and time zones as well as handling novel therapies, sites may require additional staff training, facilities, or technology. Given the industry's move toward more focused controls on shipping of various temperatures, sponsors' assessment of sites' practices could result in considerable cost savings for companies. 

Investigative sites are asking for improvements in communication to help them accommodate supply shipments and returns more effectively and efficiently. An opportunity for sponsors to conduct site assessments of their supply practices, including evaluating use of technology and IRT systems, may help in this area. Investigator meetings are another mechanism that could offer sponsors and CROs a means to address communication channels among clinical supply and clinical operations functions. Lastly, routinely and systematically collecting feedback from sites will provide sponsors with valuable insights into relationship effectiveness and improvement areas. 

, PhD, is Senior Research Fellow, Tufts CSDD, email:  

, MBA, is Director of Sponsored Research Programs and Associate Professor, Tufts CSDD; 

 is Global Director, Strategic Marketing, Fisher Clinical Services.

To whom all correspondence should be addressed

1. Swaminath, G. "Juggling Clinical Trial Supplies." 

http://www.dddmag.com/articles/2012/05/juggling-clinical-trial-supplies/

2. English, M and Ma, A.  "From Cradle to Grave: Tracking the Life Cycle of a Drug is a Complex process that Early Planning and IVR Technology can Help Ease." 

3. Kole, T. and Bedford, J. "Mitigating the Challenges of Global Trials: e-Clinical Best Practices for Managing Patients and Clinical Supplies in Emerging Regions." 

http://www.contractpharma.com/issues/2012-11/view_features/mitigating-the-challenges-of-global-trials/

4. Murphy, J. and Whitaker, S. "Streamlining Site and Patient Management." 

http://www.lifescienceleader.com/magazine/past-issues3/item/3841-streamlining-site-and-patient-management?list=n/

Articles

Feature Article

Pressure to shorten study start-up timelines puts clinical supply management in the crosshairs.

Clinical Supply Capabilities, Practices, and Perceptions Among Investigative Sites

Increasing the speed with which promising pharmacological treatments move from pre-clinical research to patient-care utilization has received increasing focus in recent years

  and is a critical goal of the National Center for Advancing Translational Sciences (NCATS), an NIH institute established in 2011.

  Some streamlining efforts focus on issues of great scientific appeal, such as the development of chips mimicking human tissues to be used to screen for toxic drug effects. Other efforts are focused on more mundane, yet important, issues such as ensuring that investigators have needed access to regulatory support and data management tools.

  Achieving more efficient translational research will entail reducing the time and expense required to conduct clinical trials in the United States.

  A report from the Institute of Medicine in 2010 delineated several key challenges to the efficient completion of multi-site clinical trials.

  This paper addresses one of the issues raised, which is the relatively long time that the pre-implementation phase, the phase between sponsor approval of a protocol and initiation of recruitment, can take to complete. 

A long pre-implementation phase is problematic in that it can significantly increase the costs of conducting the trial and reduce the speed with which findings are available, and hence, their potential relevance.

  The pre-implementation phase for multi-site clinical trials is complex and typically entails coordination among multiple institutions and among individuals with varying areas of expertise. There can, thus, be a number of potential reasons for a lengthy pre-implementation period. For example, the time required to obtain all regulatory approvals can significantly prolong the pre-implementation phase.

  There are three primary causes of prolonged pre-implementation periods, only one of which, the occurrence of unforeseeable events, cannot be avoided. A second cause is the human tendency to underestimate the amount of time a project will take to complete, which is a well-documented human bias; indeed, understanding the factors that contribute to the bias, and potential methods for countering them, has received a good deal of study.

  A third cause is problematic coordination among the entities that play a key role in the clinical trial. This paper describes the Pre-implementation Timeline Calculator, which is a tool designed to help investigators plan and coordinate the completion of the pre-implementation phase in a timely manner and presents data suggesting that the Calculator may be helpful in reducing the time and cost needed to complete the pre-implementation phase. 

The Pre-implementation Timeline Calculator was developed in working with the National Drug Abuse Treatment Clinical Trials Network (NIDA CTN). The CTN was established in 1999 in response to an Institute of Medicine report delineating the relative lack of information exchange between substance abuse researchers and substance abuse community treatment providers.

  In the CTN, substance abuse researchers work with treatment providers to design clinically meaningful trials and implement them in "real-world" settings utilizing existing staff as interventionists and clinic patients as participants. The CTN links substance abuse researchers and treatment providers through nodes, with each node consisting of a regional research and training center (RRTC), which is affiliated with a university, and multiple community treatment programs (CTPs) that work with the RRTC. Oversight of the CTN is provided by the Center for the Clinical Trials Network (CCTN). The CCTN contracts with a clinical coordinating center (CCC) to provide regulatory guidance, quality assurance monitoring, central pharmacy and laboratory services, and study supplies. The CCTN also contracts with a centralized data and statistics center (DSC), which provides statistical support and data management for CTN trials. Study oversight is provided by the RRTC of each participating CTP and by the study's executive committee, which is comprised of the lead investigator (LI), members of the LI's team, and representatives from the CCTN, CCC, and the DSC. 

The Pre-implementation Timeline Calculator

To help manage, and successfully complete, pre-implementation in a timely manner, the Pre-implementation Timeline Calculator was developed for pharmacological multi-site clinical trials. The Calculator divides the pre-implementation stage into six general tasks.  

The Calculator itself is a Microsoft Excel worksheet and is available for free at the CTN Dissemination website (

http://ctndisseminationlibrary.org/resourcespolicies.htm/

). Cells with dotted borders require direct entry of the actual date associated with the task being referenced. Most cells in the Calculator are pre-filled with formulas and locked; time-to-completion targets may be adjusted as needed by changing the value in the associated cell. Based on the date entered for "sponsor approval of protocol," recommended dates for target site initiation and the investigators' meeting are generated.  

As noted earlier, a long pre-implementation phase is problematic.

  For CTN trials, the target is to initiate recruitment eight months after receiving sponsor approval of the study protocol. While the goal is to complete the overall pre-implementation phase as efficiently as possible, particular attention is given to minimizing the time between completing staff training and initiating participant recruitment, since staffing costs constitute the majority of costs for a clinical trial; thus, it is important to minimize staffing costs at sites that are not open for enrollment. The target of holding the investigators' meeting one month prior to site initiation is based on the time generally needed to complete site preparation and quality assurance (QA) visits following the meeting and prior to site initiation. 

Instructions for using the Calculator. Utilization of the Pre-implementation Timeline Calculator to establish the pre-implementation timeline for the trial entails three steps: 					

The investigator enters dates for sponsor approval of protocol, target for site initiation, and investigators' meeting. 

The investigator and his/her team review each task and determine if there are any tasks that are not relevant for the trial or which were completed prior to the sponsor approving the protocol. For these tasks, a "dummy" date is entered into the Calculator in the "Actual Date Completed" column. For site selection tasks, the dummy date should be the date that the sponsor approved the study protocol. For all other tasks, the date completed should be the "Target Date of Completion" generated when the three dates listed in step 1 were entered. 

The investigator and his/her team determine if the "Estimated Time to Complete" needs to be adjusted for any of the tasks and adjusts the estimated number of weeks to complete as necessary. The appearance of an "X" in the "Timeline Problem" column indicates that site initiation eight months following sponsor approval may not be feasible and a later date for "Target Date for Site Initiation" should be entered. 

Commitment to the timeline should be obtained from all parties playing a key role in the pre-implementation phase (e.g., investigator, data management center, parties responsible for securing study medication and supplies, QA monitoring, etc.). The investigators' meeting should then be scheduled, avoiding both holidays and relevant professional conferences, to ensure the availability of the venue for the meeting. At the end of this process, the pre-implementation timeline for the trial has been established and should be shared with all parties playing a key role in pre-implementation, including the study sites, once they have been selected. The provision of the timeline allows each entity time to complete their piece according to schedule. 

 The following is a description of the six general tasks involved in the pre-implementation stage: 

The goal is to have the sites selected at least one month prior to the expected initiation of regulatory activities. Many clinical trials require that an institutional review board (IRB) submission be completed at the level of the site, and many sites will require that a contract/subaward be established before any work, including preparing IRB submissions, can commence; allowing a month for contract/subaward establishment can help avoid delays in initiating needed regulatory activities. Since the Calculator was created for use in the CTN, a network in which information about candidate sites, including prior performance, typically is readily available, the tool reflects the time needed to obtain a completed study questionnaire from sites and to conduct telephone interviews with promising sites. When the Calculator is used for trials requiring site visits for site selection, the "Estimated Time to Complete" number needs to be increased for the "Interview Sites" task.  

 Obtaining all needed regulatory approvals can require a substantial amount of time. In the case of U.S. pharmacological trials, this will include obtaining an investigational new drug (IND) or an IND waiver from the FDA. For many multi-site clinical trials, it will also necessitate obtaining approvals from multiple IRBs. The goal, therefore, should be to have all regulatory approvals obtained prior to the investigators' meeting so that regulatory-related delays in initiating recruitment can be avoided. 

Clinical trial data management system development often takes significantly more time than expected. The timeline for creating the data management system is based on the time required for past multi-site trials.  

4. Study materials, medications, supplies. 

The target dates for completing the operations manual and having the study medication and supplies on site are entered into the Calculator. A thorough, user-friendly operations manual is a key piece of a successful multi-site trial and generally should be completed as early in the pre-implementation process as possible, since its completion can delineate feasibility issues with the protocol that should be corrected prior to IRB submission. Clear delineation of responsibility for obtaining study medication and supplies, and securing commitment to meeting the timeline, needs to be completed as part of determining the pre-implementation timeline for the trial.  

 As noted, staffing constitutes a significant portion of the cost of conducting clinical trials and, thus, the site staff should be hired so that the time elapsing between hiring and initiation of subject recruitment is the amount of time needed to complete training and site preparation. As tracked in the Calculator, research assistants (RAs) typically are hired earlier than the remaining staff, which reflects the additional training requirements for the RAs. The other study staff can be hired approximately two weeks before the investigators' meeting, which allows enough time to make travel arrangements to attend the meeting. The amount of time required to hire staff can vary dramatically, from very little time for sites moving staff from one trial to the next, to several months for sites that need to establish a new position and complete the hiring process.   

 6. Investigators' meeting and site initiation. 

As noted, the goal is to hold the investigators' meeting approximately one month prior to the target date for initiating subject recruitment. 

Use of the Calculator to condense the pre-implementation phase

From a budgetary perspective, the lengthening of the pre-implementation period can result in staff being hired and the investigators' meeting being held without the trial being ready to start (e.g., the data management system is not complete, needed study materials have not been finalized, etc.). Evaluating whether the Pre-implementation Timeline Calculator reduces pre-implementation phase length would require that clinical trials be randomly assigned to Calculator use or to a control condition, which has not been done. However, preliminary data on the Calculator's potential to reduce the length of the pre-implementation phase is available and has been used for several multi-site clinical trials, including three pharmacological trials; these trials are referred to as Calculator trials. 

The Calculator trials were all CTN studies initiated between 2004 and 2012. Trials with which to compare the Calculator trials were samples of convenience—substance abuse pharmacological trials conducted during approximately the same period as the Calculator trials for which information about the pre-implementation phase length was available. The non-Calculator trials are four pharmacological substance abuse trials initiated between 2003 and 2011, which include both pharmaceutical and NIDA (including CTN)-sponsored trials. The time required for pre-implementation can vary according to several factors, including the complexity of the trial and the amount of staff time devoted. Thus, to provide a more stable estimate of the pre-implementation timelines between the Calculator and non-Calculator trials, average times for each trial type are provided. 

Figure 1 provides the average times taken for two segments of the pre-implementation phase: the period between having a sponsor-approved protocol and the initiation of recruitment at a study site and the period between the investigators' meeting and the initiation of recruitment at a site. As illustrated, the Calculator trials were about six months shorter than the non-Calculator trials for the first period and three months shorter for the second period. To provide an estimate of how elongation of the second period can contribute to the cost of a clinical trial, the staffing cost associated with the additional three months was calculated for a hypothetical trial conducted at 10 sites with site staffing, as outlined in Table 1. On average, there were 48 days between the investigators' meeting and the initiation of recruitment for the Calculator trials and 145 days for the non-Calculator trials. With a cost of $400 per day, per site for staff costs, the staffing costs for the Calculator trials would be $192,000 for 10 sites for the period between the investigators' meeting and the initiation of recruitment and would be $580,000 for the non-Calculator trials, a difference of $388,000. 

The goal of streamlining translational science, of which streamlining multi-site clinical trials is a component, is critical.

  Achieving this goal will entail the dedication of many investigators, as well as attention to factors that, while mundane, can have a significant impact on the speed with which promising therapeutic treatments reach patient care.

  This report addressed one challenge to the efficient completion of multi-site trials—the relatively long period of time that it can take to complete the pre-implementation phase. It discussed the use of the Pre-implementation Timeline Calculator, which was developed to help investigators to plan for, and complete, the pre-implementation phase in a timely manner. Preliminary data suggest that using this tool may significantly reduce the time and financial resources required for pre-implementation. An important limitation of the present data is the reliance on a sample of convenience for the Calculator and non-Calculator trials. However, investigators who have completed multi-site pharmacological trials have access to the length of the pre-implementation phase for their trials and, thus, can determine whether the use of a tool like the Pre-implementation Timeline Calculator may lead to time and cost savings. In general, given that the Calculator has no discernible disadvantages, its more widespread use in multi-site clinical trials seems warranted.  

, PhD, is Professor of Psychiatry and Behavioral Neuroscience; Director of Addiction Sciences Division, University of Cincinnati College of Medicine, email: 

1. Zerhouni EA. Translational and Clinical Science—Time for a New Vision. 

2. Insel TR. Invited Response to: Preparedness of the CTSA's Structural and Scientific Assets to Support the Mission of the National Center for Advancing Translational Sciences (NCATS). 

3. CTSA Principal Investigators, Shamoon H, Center D, et al. Preparedness of the CTSA's Structural and Scientific assets to support the mission of the National Center for Advancing Translational Sciences (NCATS). 

4. Dilts DM. Early Warning: An Ailing Canary in the Mine. 

5. Wang-Gillam A, Williams K, Novello S, et al. Time to Activate Lung Cancer Clinical Trials and Patient Enrollment: A Representative Comparison Study Between Two Academic Centers Across the Atlantic. 

6. Institute of Medicine (US) Forum on Drug Discovery, Development, and Translation. Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop summary. Washington (DC): National Academies Press; 2010. 

7.  Norris KP. The Accuracy of Project Cost and Duration Estimates in Industrial R&D.

8. Roy MM, Christenfeld NJ, McKenzie CR. Underestimating the Duration of Future Events: Memory Incorrectly Used or Memory Bias? 

9. Jorgensen M, Grimstad S. Software Development Estimation Biases: The Role of Interdependence. 

10. Kutsch E, Maylor H, Weyer B, et al. Performers, Trackers, Lemmings and the Lost: Sustained False Optimism in Forecasting Project Outcomes — Evidence from a Quasi-Experiment.

11. Sanna LJ, Schwarz N. Integrating Temporal Biases: The Interplay of Focal Thoughts and Accessibility Experiences. 

12. Jorgensen M. Identification of More Risks can Lead to Increased Over-Optimism of and Over-Confidence in software development effort estimates.

13. Sanna LJ, Parks CD, Chang EC, et al. The Hourglass is Half Full or Half Empty: Temporal Framing and the Group Planning Fallacy. 

Group Dynamics-Theory Research and Practice

14. Buehler R, Griffin D, Ross M. Exploring the Planning Fallacy—Why People Underestimate Their Task Completion Times 

15.  Halkjelsvik T, Jorgensen M. From Origami to Software Development: A Review of Studies on Judgment-based Predictions of Performance Time. 

16. Lamb SJ, Greenlick MR, McCarty D. Bridging the Gap Between Practice and Research: Forging Partnerships with Community-based Drug and Alcohol Treatment. Washington (DC): National Academy Press; 1998. 

Method designed to reduce the time gap between protocol approval and recruitment is examined.

Efficient Pre-implementation of Multi-site Clinical Trials

Some fresh impetus to modernizing European approaches to clinical trials may emerge from the launch last month of the new, improved Innovative Medicines Initiative (IMI)—the public-private partnership between the European Union and the pharmaceutical industry. IMI2 claims to be more than a second phase of the research-support program launched in 2008. It is not just that it will have more money (although at $4.5 billion, its funding for the next seven years is more than 50% higher). It is based on a new strategic research agenda, itself inspired by the 2013 update of the World Health Organization's report on Priority Medicines for Europe. And it places a new emphasis on the needs of patients and society, and on the potential of personalized medicine. 

In practical terms, IMI2 suggests ways that may help to overcome the problems that arise from different countries' different approaches to the conduct of clinical trials. "The acceptance of a new design in one country may not be supported by another, making the conduct of global trials challenging," it acknowledges. So IMI2 will aim to establish, train, and maintain European networks of a new breed of investigators in all EU countries. The networks  should, the partnership envisions, have "ample expertise and experience in designing and executing clinical trials for diagnosing, preventing, and treating disease as required to support delivery of clinical trials that address the priority health areas underpinning IMI2." In addition to hospitals with disease management expertise, the networks will have to include individual experts in clinical trial design, regulators, the pricing and reimbursement agencies that take part in Europe's emerging health technology assessment framework, and experts in developing and delivering appropriate training.  

These networks will also have to be able to command global recognition for their excellence, and be capable of effective collaboration with other national, European and global initiatives. Central tasks will include establishing best practice, standardized training materials, and feasibility assessment criteria. There will be a need for development of a standardized charter for clinical trial networks, including clear criteria for inclusion of sites, certification, quality control, and plans for sustainability, and these will need agreement from all key players across academia, industry, and regulators. Laboratory trial and research networks will also be required. 

The results expected will include a "significant reduction in study set-up times," as well as lower costs. These improvements will be attained, says IMI2, through increased access to clinical sites trained in good clinical practice, and up-to-date reports on each site in terms of standards of care, diagnostics, patient flow, time process for institutional review, and contracting, as well as the availability of training materials for clinical investigators. 

At a more theoretical level, IMI2 is to explore innovative adaptive designs more systematically. Noting the increased attention to probability inferences, it proposes closer scrutiny of the approach to avoid over-simplification. While "Bayesian statistical methods are being used increasingly in clinical research to minimize the number of patients included in a randomized clinical trial and decrease the chance of maintaining a patient in an unfavorable treatment arm," IMI2 says. Enumerating the potential benefits, the partnership counsels caution.  

There is much in favor of these methods, IMI2 recognizes: "Accumulating results can be assessed at any time, including continually during the study, with the possibility of modifying the design of the trial; for example, by slowing (or stopping) or expanding accrual, unbalancing randomization to favor better performing therapies, dropping or adding treatment arms, and changing the trial population to focus on patient subsets that are responding better to the experimental therapies." But, IMI2 goes on, "While paved with good intent, many designs focus primarily on obtaining efficacy"—which presents challenges when balancing the need to collect sufficient data regarding potential adverse events. Trial design and analysis can become complex and bias can be introduced through changes of the patient population over time or changes in molecular strain characteristics. "More efforts are therefore required to refine the concept of adaptive trial design," IMI2 concludes.  

At the same time, even with these advances in clinical development, efforts aimed at minimizing regulatory authorities' uncertainties about safety and efficacy of new medicines and vaccines may still leave significant uncertainty over real-world effectiveness and risk, remarks IMI2. This can impede both the speed and level of patient access, the partnership warns. The lesson IMI2 draws from this is that with healthcare decision makers increasingly assessing a medicine in terms of expected future value in real-world clinical practice, with increased emphasis on value, or the relationship between outcomes and cost, "there is a need for better ways to measure outcomes (benefit and risk) that are clinically meaningful but standardized across countries and clinical setting." No easy task, IMI2 recognizes, dismissive of glib responses reliant merely on emerging e-health solutions.  

It does not dispute the opportunity offered by the advent of digital media and the use of smartphones and tablets to develop new methods for collecting real-world benefit and risk data on the basis of more patient reported outcomes. But this presents its own challenges that still need answers—in particular in managing the collection, validation, and analysis of data, ensuring the cost-effectiveness of data collection, and complying with requirements of privacy laws and data security. A framework to address data privacy and personal integrity issues inherent in the use of health records and personal genomic data will be needed, IMI2 stresses. 

Alongside the growing demand for demonstration of value, drug development itself is progressing further toward precision medicine approaches, IMI2 points out. This, it adds, is driving the need for development of new patient-focussed clinical outcome measures and new clinical trial paradigms that can support the evaluation of benefit and risk in small stratified patient populations. Equally necessary will be infrastructures for collection and sharing of trial data, together with methods for meta-analysis of trial data to investigate outcomes across multiple stratified trials in different locations.  

The increased attention to patients that is implicit in IMI2's focus on personalized medicine is reflected in more explicit fashion throughout the strategic agenda. "Patient input will be essential to the development of new outcome measures and integrated treatment paradigms that move away from a medicine-only approach to one of a personalized care package," IMI2 says. Each chapter of the research agenda ends with a summary—more or less credible—of the intended or supposed benefits to patients.  

Core objectives include establishing "a framework with clearly defined rules, ethical standards, and data privacy measures to support the interaction of key stakeholders (especially patient groups) involved in the clinical development of new medicines and vaccines." IMI2 will aim to "develop innovative clinical endpoints which more closely reflect value to the patient," such as patient-reported outcome measures.  It will seek greater "involvement in the healthcare ecosystem" of patient and citizen needs, and mechanisms to ensure patients and citizens are "suitably educated regarding the health options available to them, as well as a more open dialogue between patient and healthcare providers." 

The program will also devote greater attention to patient adherence to prescribed dosing regimens—not just in patients with relatively minor illnesses, but also to those suffering from life- threatening conditions; it describes some of the figures of non-compliance as "staggering." This problem is set to become more prevalent as healthcare is increasingly pushed outside the hospital setting and the age of the population increases, IMI2 predicts. What it has in mind for effective adherence programs is an integrated approach with services, including clinical support and education to patients, the development of new drug delivery systems, and the development of robust, portable monitoring devices. 

The strategic research agenda also speaks of encouragement for patient and disease advocate groups to become engaged in education on the science of clinical trials and translational research, and to become involved in sample collection, data sharing, collaborative study design, and analysis. Increased participation of citizens and patients early in the R&D process also offers the opportunity to better understand the needs of each individual, the behaviors that drive poor lifestyle choices and non-adherence to prescription regimes, and, therefore, offer the opportunity to create not just medicines, but integrated treatment programs tailored towards maximizing outcomes, says IMI2. Above all, to achieve the concept of precision medicine with its tailored treatment programs, "it will be essential to better understand individual patient behaviors, societal, lifestyle, and environmental factors that influence the engagement of patients with their treatment pathways, an area which to date has received little attention." 

People getting sick in Europe may look forward to better treatments—but patients are also going to be doing a lot of hard work as this program rolls out. 

is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.

View from Brussells

New phase of innovation initiative emphasizes focus on research networks, adaptive trials, and personalized medicine, among other key areas.

A Shot in the Arm for European Clinical Trials?

The current global economical and regulatory environment has led the biopharmaceutical industry to transform the clinical supply from oversight of a domestic, linear process into management of a complex network of global demand and supply lines, addressing additional challenges. New adaptive study designs, new target diseases, and global studies require on-demand packaging and labeling methods in order to keep operating costs under control. 

These challenges create significant opportunities for clinical supply chain to drive efficiency, lower costs, and reduce lead times for drug launches. There is an urgent need to set up and deploy integrated management solutions from investigative center opening to study closeout in order to streamline the entire clinical supply chain.  

Electronic good supply practices (eGSP) ensure that the supply chain, supported by integrated e-platforms, is safe and meets its intended use while guaranteeing full traceability and accountability. This article aims at simplifying some critical steps of parallel logistics processes to optimize operational challenges faced by clinical trial stakeholders and to achieve significant savings through process rationalization and data integration. 

Clinical research logistics have not evolved to keep pace with the outsourcing of activities to contract manufacturing organizations (CMOs), contract research organizations (CROs), central laboratories, centralized ECG, and bio-imaging providers. Even though the logistics processes for clinical trial materials do not vary significantly from study to study, the supply chain remains fragmented among various subcontractors and suppliers. This results in increased complexity, redundancy, higher costs,

  and even confusion at investigator sites. 

Despite the success of interactive voice/web response services (IXRS) facilitating the logistical issues surrounding the conduct of clinical trials, no efforts have been made to integrate the supply chain of investigational medicinal products (IMPs), sampling kits, and ancillary supplies. The eGSP approach is the turnkey to streamline the clinical trial supply chain and to provide all stakeholders with the required tools to manage a specific part of the supply chain or to give the complete overview and status of all aspects of the study. 

Beyond the business process and complexity issues, a lack of software integration and functionality/gaps also causes difficulties. Packaging operations are managed through an independent control system. The IXRS systems generating orders for clinical trial kits are not usually integrated with the planning processes, which are distinct from the systems used to manage internal and third-party production and distribution operations. 

New technologies are emerging to help pharmaceutical companies distribute medicines. E-platforms help share data securely and economically with suppliers around the world, analyze the data very rapidly, and respond to sudden changes in supply and demand, while advanced tracking technologies enable them to monitor products from the factory gate to the patient.

While several solutions are available, such as clinical trial management systems (CTMS), clinical data management systems (CDMS), enterprise resource planning (ERP), laboratory information management systems (LIMS), manufacturing execution systems, business intelligence, IXRS, and SAS business analytics software applications used in clinical development, most of these are isolated applications that do not share data, resulting in delay and poor data accuracy and data availability. 

Forecasting and inventory visibility challenges can also be attributed to the fact that the CRO—to which most of the trials are outsourced—usually does not share the same platform of applications and depends more on the IXRS to provide dynamic forecasts. Thirty-five percent of businesses recently surveyed by Gartner Inc. identified the inability to synchronize end-to-end business processes as an issue, which will increase demand for supply chain management application convergence.

  In the clinical research supply chain, we struggle with functional and application silos of each stakeholder, that make orchestrating and synchronizing business processes across the stakeholders nearly impossible. 

The key success factor to streamline the collection and exchange of data is the development of secure e-platforms for capturing, gathering, consulting, sharing, and tracking all study data. The real added value, therefore, comes from the development of the e-platform best suited to support each trial. eGSP incorporates the good practices of integrating electronically all information systems related to the supply chain in clinical trials. 

A range of internal stakeholders, including clinical operations, regulatory affairs, clinical quality, manufacturing and supply, and the qualified person (QP) are all involved in various aspects of ensuring adequate supply. Involvement of the right people who know the business is critical in the setup of an eGSP approach. Those from clinical operations, clinical supply chain, regulatory, and workers in the plants should be involved in the early stage of  trial development to review process maps and gather feedback on how the new system would operate. Typical stakeholders who should be involved in eGSP implementation are: 							

Project manager of each involved party (sponsor, CRO, CMO, central lab, core lab): coordinating study setup phases and seeking optimization of stakeholders' involvement

Production specialist: considers all aspects bound to production

Packaging specialist: focusing on packaging issues

Regulatory expert: ensuring all regulatory requirements are met

Warehouse manager: guaranteeing operational feasibility of deployment steps involving the warehouse

Distribution specialist: safeguarding distribution from a logistical perspective

Investigative site expert (e.g., head of CRAs): mastering all practical aspects bound to site staff involvement

Such stakeholders must have a clear operational view on their own business as well as a proven experience in the collaboration with other involved departments/vendors/CROs. 

The design of the clinical study protocol is a mandatory first step in the application submission and approval process of a clinical trial. It is the starting point and reference document throughout the entire duration of the study and details the background of the study, the objectives, the clinical design, Inclusion/exclusion criteria, treatment of subjects, reporting, data collection, and many other topics. Surprisingly, none of the topics from the protocol describe logistics, although one can consider the development of the study as a huge logistical process. While logistics operations might be out of sight, logistics is under significant pressure to deliver near-perfect performance under more complex, risky, and difficult business conditions. Many reconsiderations based on previous experiences demonstrate the importance of defining the logistics design sooner, if not already during the development of the clinical study protocol. This path becomes increasingly critical with the adoption of new study designs such as adaptive trials. 

When considering the percentage of logistics in the total cost of a project and knowing the current financial pressure on the pharmaceutical industry to reduce costs, it is urgent that all parties involved in the practical implementation of a study join their efforts in achieving the most cost efficient and seamless clinical supply chain. The eGSP is the best approach in this strategy, but how can it be ensured that this e-platform is set up in such a way that it allows for each specific clinical trial to collect and centralize the appropriate information at the right moment and in the most appropriate way? There is need to outline the supply chain processes of all materials (i.e., IMPs, sampling kits, biological specimens, ECG, bio-images, ancillary supplies) and to determine the roles and responsibilities of all parties involved in the "clinical supply protocol." The clinical study protocol brings together the clinical expertise and the logistics expertise and will allow the design of the optimal supply process for a study, ensuring operational and financial efficiency. 

For every item in the clinical study protocol, the supply chain implications are identified and fully described. This process should not be unilateral or separate, but should ideally be done in parallel with the clinical study protocol. Supply chain aspects could also influence some aspects from the protocol. 

The structure of the clinical supply protocol should be clear and practical: 							

Product stability, including packaging, storage, transport requirements

Product-related regulatory requirements (may influence the choice of participating countries)

Data format requirements (will determine barcode type, RFID)

Specimen types (can influence the choice of collection devices, storage, transport, and lab processes)

Reporting format (has an impact on the choice of reporting tools, definition of KPI's) and required ancillary supplies (can impact several site-related activities)

Data to be used by different parties throughout the logistics processes should be outlined in the clinical supply protocol. Typical supply chain aspects consist of production, warehousing, distribution/transport, and returns. For all these activities, specific quantifiable information (volumes, timelines, etc.) should be collected. Specific software tools used by the different subcontractors should be listed and their interface requirements with the e-platform identified. Finally, the roles and responsibilities of all stakeholders involved in the protocol supply chain should clearly be assigned and validated by each party. 

Based on such information summarized in a well-elaborated clinical supply protocol, the set-up of the project in the integrated e-platform will be an easy and smooth process. The framework of the clinical supply protocol provides a single, integrated landscape to manage the complete clinical supply chain by addressing all challenges faced by the different logistics stakeholders. 

Study conduct: From site opening to site close-out 

In an eGSP approach, upon availability of the clinical supply protocol, operational processes must be delineated step-by-step in order to ensure appropriate interaction between the following stakeholders involved: 							

The vendor(s) for data collection and patient randomization services (eCRF and IxRS)

The supply chain stakeholders (CMO, central lab, core lab)

The investigating center (investigator, study nurse, pharmacist)

There are three essential processes that are supported by integrated e-platforms to allow these stakeholders to best interact with an innovative eGSP approach: 					

The clinical supplies process supported by an e-platform is very comprehensive. According to their access rights, the e-platform will involve the related stakeholder to ensure clinical supplies, but also sampling kits and ancillary supplies are available on-site. The supply process starts with the involvement of the project manager (from the CRO or sponsor) to give a "green light" through the e-platform in order to release shipping orders.  

Once green light is given for an investigator site, a shipping order (built in a suitable format and according to a predefined structure) is sent to the CMO for automated integration into its system. A shipment date is associated with each shipping order and the site is immediately notified when the shipment will be performed. Just-in-time packaging and labeling is then carried out as well as the connote (air waybill) preparation. Shipment information (content and connote number) is confirmed in the e-platform that will promptly notify involved parties (sponsor/CRO and site). Shipment confirmation will also trigger a notification to the parties as well as the proof-of-delivery confirmation. The person on site responsible for receiving the shipment will be prompted to confirm shipment content and integrity (received in good state or damaged, correct quantities, etc.) by accessing the e-platform and completing the necessary online form. This will allow the CMO and project manager to be notified accordingly. Should some actions be required following the confirmation performed by site (e.g., goods received damaged), the e-platform will trigger appropriate notifications to the CMO and project manager, allowing a timely follow-up with the sites.  

eGSP-driven approach focuses on overcoming operational challenges through data integration.

Optimizing Trial Supplies Via Integrated e-Platforms

Consumer groups, research organizations, and members of Congress are pressing for more inclusive clinical research. Critics of current policy claim that a lack of information on how drugs and medical products affect certain patient populations increases the risk of inappropriate use and improper dosing. A prime example is FDA's recent decision to lower the dose for women of the sleep medication zolpidem due to slower metabolism of the drug by women.  

Clinical trial homogeneity continues to attract attention on Capitol Hill. One new legislative proposal would require FDA to ensure that clinical trials supporting products granted expedited approval are sufficient to determine safety and effectiveness for both men and women. And a long list of Democratic women in the House have requested that NIH make demographic data public through the 

The Affordable Care Act of 2012 included several provisions designed to reduce racial disparities in healthcare, including one creating the Office of Minority Health (OMH) at FDA. OMH is charged with promoting "meaningful participation" of minorities in clinical trials, a topic that was examined at an April public hearing on the challenges of collecting and analyzing research information on demographic subgroups. The comments aired at the hearing will shape an FDA action plan to improve the collection and analysis of data on the sex, race, ethnicity, and age of clinical trial participants, which the agency hopes to finalize this year.  

A sign of the times is that FDA is "actively encouraging" drug companies to include men in breast cancer trials. In an FDA consumer health information posting, Tatiana Prowell of the Office of Hematology & Oncology Products (OHOP) in the Center for Drug Evaluation and Research (CDER), notes that men historically have been excluded from these studies, but that information is needed because men respond differently to treatment. 

Similarly, OHOP data from multiple clinical trials submitted to FDA in applications for prostate cancer treatments indicates frequent under-representation of racial minorities. In an article published online June 25, 2014 by the journal 

, OHOP director Richard Pazdur and colleagues report limited minority participation in 17 prostate cancer trials conducted over the last 20 years and involving almost 40,000 patients.   

Developers of medical devices also face more specific requirements for including women in clinical studies from FDA's Center for Devices and Radiological Health (CDRH), which seeks to finalize draft guidance issued in December 2011 on evaluating sex differences in device clinical studies. CDRH medical officer David Strauss noted in a June 23, 2014 posting on 

 that women represented only 22% of patients in clinical trials for cardiac resynchronization therapy (CRT) devices, but that women benefit more than men from these pacemakers designed to prevent heart failure (see article by Strauss and colleagues, published online June 23, 2014 in 

The Journal of the American Medical Association: Internal Medicine

Sponsors, moreover, may feel pressure to examine whether preclinical toxicity testing sufficiently balances female and male animals and cellular cultures.  NIH recently adopted such a policy to ensure that the clinical research it funds fully assesses sex differences in patients.  NIH has required inclusion of women in clinical trials for more than 20 years, but not in preclinical tests, and researchers tend to rely more on male lab animals, NIH acknowledged in its May announcement. Now NIH grant reviews will consider the balance of preclinical testing in evaluating proposals to avoid obscuring important sex differences in later studies involving human subjects.  

Hormone differences, body composition, and metabolism can alter response to medicines, according to a report in 

 (June 12, 2014). Women get greater relief from opioid painkillers but may become addicted more easily than men; women respond better to certain antidepressants than men; and less stomach acid may cause women to feel the effects of antianxiety medication faster.  

For such reasons, research sponsors say they are working hard to broaden enrollment in clinical studies, but fear that stricter requirements for patient subgroup inclusion will make it harder and more expensive to launch and complete clinical trials. NIH's landmark A4 Alzheimer's study, for example, aims to uncover clues for preventing or halting the disease by assessing long-term response to treatment in 1,000 asymptomatic adults aged 65 to 85. But enrollment has been slow, as many elderly individuals appear leery of learning if they have the amyloid plaque build-up indicative of future disease, according to a report in 

 (June 20, 2014). Moreover, the study requires 20% of enrollees to come from under-represented demographic groups, such as blacks and Latinos, who appear even more reluctant to sign up. Many sites have voiced concerns about recruiting that "one-fifth." 

News

Consumer groups, research organizations, and Congress are pressing for more inclusive clinical research.

Clamor Grows to Expand Trial Participation of Women & Minorities

Innovation in oncology continues to dominate the drug development pipeline, with accelerated approvals, increased funding and awareness, and an overall pipeline of almost 2,000 active products under study accounting for one-third of all pharmaceutical R&D. However, while many oncology indications are experiencing success in life extension with overall five-year survival rates at more than 66%, others such as lung cancer are struggling to achieve the same results, with a mere 16.8% of patients achieving five-year survival. While these rates may be low, innovation in lung cancer is at an all-time high; extending survival of lung cancer patients has become a large industry investment. 

However, an interesting finding is that the U.S. has remained cost neutral over the last five years in R&D cost per-patient spend, in addition to remaining visit neutral in the area of lung cancer research (see chart). Ex-U.S. has experienced the opposite—with a correlation between increased patient visits and increased per-patient spend. What is fueling this increase in activity? Is this purely a result of globalization of research over the past five years? Or perhaps the U.S. has become more efficient in execution, thus controlling spend, but with little new outcomes.  

Breathe Easier: Cancer R&D Innovation Puts Strong Focus on the Lung

Over the past two decades, the decision process for siting overseas clinical trials has become more complex for U.S. pharmaceutical companies. Once a straightforward analysis rooted in time and money, longer-term strategic issues are now pushing to the fore, combining to make these high-investment, high-risk calls even more multifaceted. 

These challenges become particularly focused for small pharmaceutical and biotechnology companies with time and resource constraints. There is also a need for smaller companies to lay the groundwork for rapid adoption of their approved product, particularly with diseases unique to certain populations or regions. In those situations, a "hearts and minds" effort with local hospitals and doctors can build a comfort level for rapid use of the drug. Orphan drugs targeting smaller populations can live or die commercially by missteps in the human aspect of the trials conducted in the target geographic populations...poisoning the well, as it were. 

Treatments, cultures, and attitudes manifest themselves in different ways in different countries on different continents. One example in our own experience revolved around early brain trauma following subarachnoid hemorrhage. Japan offers a unique opportunity for study in this area, as its medical system is geared towards treating all serious headaches as potential indicators of a severe underlying brain injury. Accordingly, diagnostic and treatment habits and practices are directed at rapid intervention in hopes of preventing a more serious outcome. Where U.S. clinicians may routinely wait 24-48 hours to see if headaches persist, the Japanese medical community tends to act earlier, presenting a unique opportunity for clinical research. Conversely, a drug that is efficacious for early symptoms may not be if given in a later phase of progression. While that complicates the decision-making process for an individual clinical trial strategy, the opportunity to test for early intervention efficacy is a powerful incentive to test in Japan.  

At Prolong, the primary focus of our clinical research is on sickle cell disease (SCD), a genetic disease that presents in multiple comorbidities. Ranging from such diverse indications as dactylitis, vaso-occlusive crisis, stroke, leg ulcers, and several cardiac/pulmonary abnormalities, sickle cell disease is both an orphan indication in the U.S. (with about 100,000 patients) and a continent-wide problem, with 12 million sufferers in Africa. The Middle East and South America are seeing rising SCD populations as well. 

Clinical trials are, of course, the basis for a drug's approval and comprise the main body of evidence for safety and efficacy. Of critical consideration is that product licensure is based on assessing the totality of the scientific evidence. This longstanding concept has formed the basis for many food, drug, and device approvals/rejections around the world.  

The totality of scientific evidence is not limited to where clinical trials were conducted or by the unique habits and practices of a given geographic location. Accordingly, a clinical development plan to secure the totality of evidence can be parsed among locations depending on the strategic objective(s). Early acute intervention versus staged chronic treatment requires very different clinical trial designs, protocols, and monitoring strategies. It may also require different global locations to successfully acquire independent data sets that, together, will form the totality of scientific evidence.    

In short, international siting for trials offer opportunities for enhanced patient populations or treatment environments more appropriate to a trial's requirements. At the same time, once these benefits are identified, various concerns must be weighed to ensure that the trials, if conducted in future key markets, take that into consideration when interacting with local clinicians and patients. 

A Closing Thought

Longer-term strategic issues are making already high-investment, high-risk decisions to place studies overseas even more complex.

Strategic Approach Needed for International Clinical Trials

For study volunteers, clinical trial medicine kits represent one of the most tangible aspects of their participation experience. A study volunteer's earliest impressions of a clinical trial are influenced by the medicine kit packaging and its instructions. And the ease with which study volunteers learn how to follow instructions and take their clinical trial medicine throughout the study, as required by the protocol, plays an instrumental role in ensuring that volunteers have a safe and positive participation experience. 

Despite the importance of clinical trial medicine kits, surprisingly, very few if any clinical supply professionals have ever solicited feedback among study volunteers. There are many reasons why this is the case. Historically, most clinical supply decisions have been regarded as tactical and secondary to other scientific and operating decisions.  As a result, decisions associated with the design, production, and delivery of medicine kits have often had to be made under very tight timelines with little flexibility for accommodating outside input. In the past, many sponsors and contract research organizations (CROs) have been reluctant to interact with study volunteers for fear that they may cross the purported line prohibiting them from ever communicating with patients. And as we have seen in many areas of clinical research, historically, some professionals have chosen to downplay the patient's needs and perspective believing that they knew best.   

To address this unique opportunity to solicit feedback from study volunteers, the International Society of Pharmaceutical Engineering (ISPE) —a trade association serving technical, manufacturing, and clinical supply professionals—in collaboration with the Center for Information and Study on Clinical Research Participation (CISCRP) conducted a major research program among a large community of study volunteers. This column summarizes the high-level results of the research and provides not only baseline data for comparisons with future research efforts, but also offers insights into ways that medicine kit design and implementation can be better leveraged to improve study volunteer experience. 

A detailed report of the findings of this study is available on the ISPE web site  (

An online survey—approved by an ethical review board—was conducted between May and September 2013.  Globally, study volunteers were targeted using a number of outreach approaches (e.g., solicitation via investigative sites; social media communities; large online communities engaged with CenterWatch and with Acurian, a patient recruitment provider). Those who had received clinical trial medicine kits at home in a Phase II or III clinical trial within the past three years were invited to respond.  

In all, 1,425 study volunteers completed the online survey. Although global responses were solicited, nearly all completed surveys came from study volunteers based in the United States, rendering the results representative of a U.S. population only.   

This respondent base had excellent gender, age, and therapeutic area representation. Respondents received their study medication in a variety of formats: 42% in bottles; 30% in blister packs; 15% in syringes; and 8% each in inhalants or topical creams. The majority of respondents (76%) received only one clinical trial medicine in their most recent trial; 24% received more than one. 

Overall, study volunteers gave extremely positive ratings of their clinical trial medicine kits: 77% said that their medicine kit was "Very Easy" to use and 13% "Somewhat Easy." Bottles, topical creams, and inhalants received a relatively small proportion (4%-5%) of study volunteers reporting difficulty using them. A much higher proportion of study volunteers had difficulty using blister packs (12%) and syringes (8%).    

An equally high proportion (91%) of study volunteers reported that it was "Very" and "Somewhat" easy for them to store their medicine kits at home regardless of medicine format. Six-out-of-ten study volunteers said that the design and layout of their clinical trial medicine kit helped them take their study medication on schedule. Approximately one-third said the design and layout was not helpful in this regard. Blister packs received the highest rating for its design and layout in helping study volunteers adhere to a schedule.   

Unique feedback from patient survey could help inform future clinical supply design and implementation.

Applied Clinical Trials-08-01-2014

Clinical Supply Capabilities, Practices, and Perceptions Among Investigative Sites

Efficient Pre-implementation of Multi-site Clinical Trials

A Shot in the Arm for European Clinical Trials?

Optimizing Trial Supplies Via Integrated e-Platforms

Clamor Grows to Expand Trial Participation of Women & Minorities

Breathe Easier: Cancer R&D Innovation Puts Strong Focus on the Lung

Strategic Approach Needed for International Clinical Trials

Study Volunteer Insights into Clinical Trial Medicine Kits

Fair Market Conundrum: Solutions for Sponsors & Sites

EFGCP Warns About Risks of Overprotecting Data

Applied Clinical Trials Digital Edition August/September 2014