n the past, numerous objections were raised to working with patients in designing and implementing clinical trials: not relevant, not scientifically valid, not allowed, not efficient, not cost effective, and so forth. One by one, these objections have proven to be myths. In fact, all accumulating (real world) evidence points to the opposite: When done well, working with patients in clinical trials is relevant, scientifically valid, allowed, efficient, and cost effective.

Patients bring a unique and needed expertise that complements and enhances (not replaces) expertise offered by science and medicine. Experience-based patient expertise offers value to several dimensions of clinical research:

• Studies co-designed with patients recruit better and faster because they are more relevant, more understandable, and easier/better to participate in.
• Studies which inform and support participating patients throughout, have fewer drop-outs; missing data (i.e., study drop-outs) remains the biggest scientific challenge to any clinical data set.
• Investments in working with patients (in staff, time, and money) while designing protocols yields exponential returns (e.g., the NPV and ENPV increases can exceed 500-fold the investment, as this study found).
• Similar to requiring ethics approval of the protocol and all participants’ informed consent, patient involvement is becoming a requirement for study funding and publication (e.g., British Medical Journal submissions, Patient Centered Outcomes Institute funding, and UK National Institute of Health Research funding).
• Last but not least, health authorities increasingly recognize that patients are needed as experts (e.g., see recent FDA and EMA statements).

Any clinical research sponsor ignoring these new realities will pay the price of lower likelihood of health authority approval, limited payer/HTA approval, subsequently creating limited access and thus lower appeal to potential investors.

Calmer Waters or Storms Ahead?

Working with patients is quickly becoming the new norm. The tipping point of the patient engagement journey in clinical research in fact may already be passed, a bit like having rounded a cape and discovering a new ocean. Can we hope this means calmer waters lie ahead for patient engagement in clinical trials?

Unlikely. A few storms are already gathering on the horizon:

• Even if clinical research sponsors perfect patient engagement, this will remain rather meaningless if other stakeholders (including health authorities, HTAs/payers, Health Care Providers, etc.) question the results of patient-co-produced research. Good collaborative initiatives to align stakeholder expectations and standards are starting, have already been started and remain in progress, but a lot more work remains to be done (also in harmonizing these efforts).
  • FasterCures Patient Engagement Frameworks and Principles
  • Patient-Centered Outcomes Research Institute (PCORI) Guidance on Design and Conduct of Trials in Real World Settings
  • Clinical Trials Transformation Initiative (CTTI) Patient Engagement Collaborative (PEC)
  • Patient Focused Medicines Development (PFMD)
  • Innovative Medicines Initiative–Patients Active in Research and Dialogues for an Improved Generation of Medicines (IMI-PARADIGM)
  • Council for International Organizations of Medical Sciences (CIOMS) Working Group XI – Patient Involvement
• The science of patient engagement/involvement is still relatively new and will evolve only by applying it, meaning that some current approaches may not lead to the desired outcomes. Patients are ready for this risk–who else is?
• Although medicine development is essentially global, expectations and possibilities to work with patients vary hugely between and even within countries, as they do across and even within different diseases and conditions. This lack of commonality can lead to unnecessary complexity, duplication, and inefficiency similar to what was experienced in R&D and technical dossiers before the ICH.
• A minority of today’s patients participate in clinical trials. We must make it easy for patients to find and understand studies that may be relevant to them; several promising initiatives, many actively supported if not driven by patient groups and patient advocates, are in progress to address this, under the aegis of these and other organizations.
  • Cancer Research UK
  • National Kidney Foundation
  • LUNGevity
  • Cystic Fibrosis Foundation
  • Alzheimer’s Association
  • Research Match
  • National Comprehensive Cancer Network
• Because a minority of today’s patients are willing and able to work with sponsors in clinical development design, sponsors are finding themselves in competition for this scarce resource. Initiatives like EUPATI, the NCRO Consumer Forum, and others address this important need.
• Remuneration for patient participation that goes beyond compensation for relevant direct costs (such as travel) is increasingly mentioned as a way to increase patient study participation, and also as an area that needs mutually recognized standards.
• As we aim for medicine to be more precise (even personalized), driven by scientific advances, personal needs and expectations, should clinical research outcomes also become more personalized? Are individual rather than standardized endpoints our future? How ready is our statistical and analytical toolkit for that scenario?
• How will science theory and clinical practice deal with the reality of multi-morbidity and multi-medication? Today we know that, especially in the aging, multi-morbidity and multi-medication are the clinical reality, while they remain routinely excluded from clinical studies as potential confounding factors. Hence, those studies lead to conclusions that do not apply to the real life population. This tension between scientific rigor and clinical reality continues to grow.
• As (“messy”) real world data become the largest source of data on any given compound, what happens to the value and durability of smaller (and “cleaner”) Randomized Clinical Trial data sets that lead to regulatory and payer approval?
• What will be the future value and shelf-life of these approvals? What is the benefit-risk profile of the investments needed to gain these approvals in the first place?

There will undoubtedly be more and different storms on our journey, but the good news is that we are no longer traveling alone. Above all, each and every one of these gathering storms is more than a challenge–it is a REASON for patient engagement.

The title of our article is inspired upon The Patient Will See You Now by Eric Topol, Basic Books, 2015