This is an extract from an exclusive free whitepaper that explores whether clinical trials are truly patient-centric yet. Download the full report here.
There are few validated clinical studies demonstrating a universal experimental design for every type of clinical trial. In fact, with the complexity of clinical research, the cost, and the difficulty in patient recruitment, adherence, and retention, a new approach is mandatory.
Patient recruitment remains the biggest hurdle to completion of a clinical trial. According to a Tuft's study, two-thirds of sites don't meet the enrollment requirements for a given trial.1 A CenterWatch report revealed that dropout rates of 15%-40% are not uncommon.2 Dropouts lead to inferior data, low staff morale, and increased trial costs.
Patients often face daunting challenges in participating in clinical research. In fact, they may not even be aware that there are clinical trials seeking volunteers. A survey conducted by Harris Interactive in spring 2000, found that 8 out of 10 cancer patients were unaware that clinical trials were an option available to them.3
The reality is that potential subjects are afraid to enroll in a clinical trial because of their negative perceptions. There is often a mistrust of industry-sponsored trials among the public. If they are aware of a research opportunity, there are issues that make it difficult or impossible to enroll such as locating a convenient trial site, the amount of travel involved, time from work, and transportation costs may be associated with participation.4 Patients may have to leave the care of their regular doctor which can be emotionally traumatic. Once a patient decides to enroll, she must confront the extensive paperwork associated with the informed consent process. These feelings and experiences make difficult the already difficult decision about whether to join a trial.
New trial design models have patient-centricity built into their design and will be more efficient at organizing, delivering pertinent data and patient communication.
- PCORnet: A model for a new type of trial design was developed by the National Patient-Centered Clinical Research Network, an initiative that was part of the Affordable Care Act. Made up of clinicians, researchers and patients in collaboration with communities, it uses the vast amount of electronic data already present from electronic health records, patient surveys, and shared data from trials, to design and fund high priority research. Patients play prominent leadership roles and are involved from the start of the study and are an integral part of study design to dissemination of results. Community involvement is critical to their mission and data source.
- Crowd sourcing5 is the practice of obtaining needed services, ideas, or content by soliciting contributions from a large group of people, especially from the online community, rather than from traditional employees or suppliers. An offspring of the internet and social networking, it can be used by both researchers and patients. Researchers and lay people can have their protocols presented to the group for comment. Recruitment comes from referral by interested patients. PatientsLikeMe and 23andMe are the leading operators of researcher-organized, crowd sourced health research studies.
- Clinical Trial Management Software Products.6 A typical CTMS defines and manages all of the activities that span the lengthy and rigorous clinical trial process such as clinical program/project management, trial and site planning, complete collection of data sets, study management, study financials, clinical supply management, protocol and study documentation, data analysis, and clinical learning and training. There are a number of CTMS systems that should meet the needs of any type of study design need.
- Adaptive trial design7 is defined as a study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypothesis based on analysis of interim data from subjects in the study. Aspects of the trial that can be changed include study eligibility, randomization procedure, treatment regimens, sample size, primary and secondary endpoints, and analytic methods. The biggest advantage of this design is its flexibility. The biggest disadvantage is the improper application of the concept to reform incomplete data sets of failed models into 'meaningful outcomes'. Excesses of this approach can end up diluting rather than strengthening the concept of patient-centricity if overlooked.
- Consortiums of competitors8 is an integration of research professionals from multiple sectors who have historically been 'competitors'. They share governance, financial outlay, patients, and risk along with resources, knowledge, and expertise. Novartis, Lilly, and Pfizer are developing such a system that allows patients to search for clinical trials and study information on a patient portal.9
- Explanatory trial design10 is used to describe trials that aim to evaluate the efficacy of an intervention in a well defined and controlled setting. Explanatory trial is the best design to explore if and how an intervention works, and the whole experiment is designed in order to control for all known biases and confounders so that the intervention's effect is maximized.
- Pragmatic Trial Design (also known as practical or naturalistic) is an emerging concept designed to evaluate the effectiveness of interventions in real-life routine practice conditions. Studies are designed with input from health systems which produce evidence that can be readily used to improve care. By engaging health systems, providers, and patients as partners, pragmatic research accelerates the integration of effective research, policy, and practice.
- Bayesian Research Design.11 Central to this model of drug development are novel tools, including modeling and simulation. This type of research design combines the data from biologic, pharmacologic and statistical modeling. These three types of data subsets are used for modeling throughout the drug development process to maximize the quality of data obtained.
- Virtual clinical trials. These type of clinical trial relies heavily on technology by recording body data that is sent to the home research site. It provides patients with convenience and ability to connect with the study group. For the research team, it provides constant availability of data and study personnel can visit the home for drug administration and follow-up care. For sponsors, it allows trials in rural areas and with patients who are elderly and infirm.
- Qualitative research12 methods add to our understanding of complex social; cultural environments, the manner in which people behave and communicate, and their understanding of the world and their place within it. Qualitative components of trials serve several purposes including determining the best methods of patient recruitment; developing research hypotheses and instruments; helping to explain findings; and understanding whether interventions can and should be implemented, by assessing their acceptability to patients and healthcare professionals.
- Molecular classification.13 The advent of personalized medicine and precision medicine coupled with advancing technologies is enabling new trial designs that match patients to the right genomic- or immune-targeted drugs. This is particularly useful in cancer clinical research as well as targeted chronic diseases where molecular classifications are more commonly performed.
It boggles the mind when envisioning the almost limitless possibilities for research design. There is no reason why a study cannot utilize more than one complementary approach. The real challenge is using technology to enhance research and not be run by it.
This extract is part of a whitepaper that asks whether patient-centricity is truly at the core of clinical trials. Download the full whitepaper for free here.
1. Tuft’s Center for the Study of Drug Development. Drug Developers Actively Improving Efficiency of Clinical Trials. Tuft’s CSDD Impact Reports, April 26, 2011 http://csdd.tufts.edu/news/complete_story/rd_pr_apr_2011
2. Tointon A. The issue of patient retention in clinical trials. Center Watch On Line, Monday, June 27, 2016. http://www.centerwatch.com/news-online/2016/06/27/issue-patient-retention-clinical-trials/
3. Most cancer patients say they are unaware of clinical trials survey. Cancer Network, December 2000. http://www.cancernetwork.com/articles/most-cancer-patients-say-they-are-unaware-clinical-trials-survey
4. English R, Lebovitz Y, Giffin R. Transforming clinical research in the United States: challenges and opportunities. InWorkshop Summary, 2010. http://www.nap.edu/catalog/12900/transforming-clinical-research- in-the-united-states-challenges-and-opportunities
6. Top clinical trial management software products. Capterra, http://www.capterra.com/clinical- trial-management-software/
7. Food and Drug Administration. Guidance for industry: Adaptive design for clinical trial research for drugs and biologics. Federal Register, 2/26/10. http://www.fda.gov/downloads/ Drugs/.../Guidances/ucm201790.pdf
8. Tufts Center for the Study of Drug Development. Outlook 2014. http://csdd.tufts.edu/files/uploads/Outlook-2014.pdf
9. Neumann UB. Transforming the clinical trial enterprise: Patient-centered clinical trials. Eyeforpharma Symposium, Rutgers Business School, 2014. http://www.business.rutgers.edu/sites/default/files/user_files/lerner/Presentation_Ulrich%20Neumann_Patient%20Centric%20Clinical%20Trials_10.22.2014.pdf
10. NIH Healthcare Systems Research Collaboratory. Introduction to pragmatic clinical trials. https://www.nihcollaboratory.org/Products/Introduction%20to%20Pragmatic%20Clinical%20Trials.pdf
11. Orloff J, Douglas F, Pinheiro J et al. The future of drug development: advancing clinical trial design. Nature Reviews. 2009; 8:949-957.
12. Rapport F, Storey M, Porter A, et al. Qualitative research within trials: developing a standard operating procedure for a clinical trials unit. Trials 2013;14:54.
13. Hoadley KA, Yau C, Wolf DM, et al. Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across tissues of origin. Cell 2014;158:929 - 944.