Nancy Meyerson-Hess is an internationally renown expert for clinical operations and an Associated Partner of admedicum® Business for Patients. She has cooperated directly with patients related to clinical trial design, recruitment and retention on numerous occasions.

• After review with clinical trial providers and investigators, two major aspects seem to drive the resistance to enroll and/or drop out of the trial: a high number of visits to treatment centers far away from home and overwhelming obligations for documentation several times a day. The travel time and inconvenience to the patients and care givers has a negative influence upon motivation to participate in the clinical trial and/or to remain in the trial over an extended time of six months.
• The company decides to work with a questionnaire to patients who were interested in participating but decided against it, and to patients who dropped out of the trial. The objective of the questionnaire is to confirm the previous findings and to understand which changes are needed to make those patients enroll and stay in the trial respectively.
• The company requests the involved clinical research organizations and investigators to ask these patients to fill out the questionnaires or to provide information. Most of the patients respond positively to the request and are open to provide their input.
• With the outcome of the questionnaires, the company sits down with some of the physicians for review and sets priorities for adapting the clinical trial protocol.
• The revised version is presented to a small group of coordinating investigators and vendors and a patient from each involved site. 
• The final revised clinical trial protocol reflects the input from patients, investigators and vendors, in as far as possible. The company also introduces new information targeting patients through newsletters, publications and indirectly via investigator information days. All of these changes need to be submitted and approved by the respective ethics committees or review boards as appropriate.
• Following implementation, recruitment picks up and retention improves, however the clinical trial still takes longer and costs more than expected.

Once the issue was identified, the company took reasonable measures to understand the patient perspective. The questionnaire was the result of homework with vendors and investigators. Additionally, the company did a good job reaching out to patients they had to convince, rather than those on the trial that are most simple to reach.

Patient involvement early in the design of the first clinical protocol would have significantly reduced the challenges met. Early engagement is an opportunity for direct exchange, to identify and bridge gaps in understanding and to come up with practical, innovative approaches to drug development.

The company did not have a formal process in place for patient involvement. Establishing such processes is time-saving and forward thinking.

There is evidence, including insights from FDA and EMA, on the positive impact of patient engagement on recruitment and retention in trials. Both aspects are often negatively influenced by the logistics of the trial and frequent visits to the investigator site, which disrupt a normal routine or work. Patient involvement in the design of clinical trial is therefore highly recommended. Here is some evidence that can help your internal review of the benefits:

• How to Guide on Patient Engagement in Clinical Trial Design by PFMD

• The DIA Patient Engagement Study reported reduced screen failure rates, faster patient recruitment rates, improved subject retention rates, reduced numbers of protocol amendments, and a greater number of patient relevant endpoints as positive aspects of patient involvement.

• The FDA Executive Summary Patient Engagement Advisory Committee leads you to further publications and materials that give guidance regarding patient involvement related to clinical trials.

• The Tufts Center for Drug Development Impact Report reported that 57% of all protocols, across all phases, have at least one substantial global amendment. The most frequent changes stem from amendments associated with modifications and revisions to study volunteer demographics and eligibility criteria. Based on the additional time and costs, it seems more cost efficient to reduce amendments by involving patients early on in the trial design and protocol discussions. 

• EUPATI's article on collaboration in an oncology trial shows another good case study for insightful involvement of patients in an oncology trial by Sanofi in France.

The US based Clinical Trials Transformation Initiative (CTTI) developed some useful tools:

• CTTI Recruitment Tool Decisiontree provides a checklist that helps you to define “when” to involve other stakeholders.

• CTTI Recruitment Tool Stakeholder helps you to prepare a strategy regarding which stakeholders to approach and for what reasons. 

Please keep in mind that stakeholder involvement means really giving patients a chance to understand and express themselves, rather than guessing what a minimally burdensome trial design is. The patient knows best!

Involving patients in clinical trial planning yields a number of opportunities that go beyond successful recruitment and retention alone. Examples are the critical review of primary and secondary clinical trial endpoints, patient reported outcomes and the patient view on benefit-risk assessment. However, all of this requires resources, time and budgets. Therefore getting senior management buy-in early on is a key to success.

Remember that although there is an obligation to publish your clinical trial, this does not provide individual trial participants with information regarding “their” participation in the clinical trial. Please don’t forget the patient experts you worked with, once the collaboration comes to an end. Prepare final information regarding what suggestions will be implemented, which ones will not, and provide reasons why.. It is good to have agreement on feedback to involved patient experts before trial commencement. And again, patient experts and investigators can probably tell you best what they would like to know from this excersize. 

If you want to go deep we recommend the following multi-stakeholder best practice sources:

• The EUPATI guidance and toolbox for involvement of Patients in R&D can be downloaded at www.eupati.eu. Although designed primarily for patients, the EUPATI materials also provide a basis for collaboration for industry. 
• Page 4 of the EUPATI Guidance for patient involvement in ethical review of clinical trials may also be of interest  as guidance for involvement of patients in the definition of the ethical conditions for clinical trials
• Last but not least the DIA Patient Engagement Considerations Guide is a source for many important aspects when considering patient collaboration in R&D (see pages 28 to 32 in particular).