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“The study was terminated due to poor rates of recruitment, continuation, and engagement.” Or as the academic would say: “The trial did not reach sufficient statistical power.”
Unfortunately, the worst case scenario of early termination of a project is not uncommon in clinical research.
Clinical trials as well as non-interventional studies (NIS) fail to reach meaningful results simply because too little patients/ subjects take part in the study in the first place, or too many violate the therapy scheme, leave questionnaires untouched, or suddenly decide to leave the study.
But why is that? You will agree that patients do not “break the rules” out of spite.
In the end, the ultimate motif for participation may become irrelevant if you, as a patient, do not feel taken seriously, included, represented, involved or informed.
Have you ever taken part in a clinical or observational study yourself? Even if not, find yourself in the position of the patient: Why would you like to be part of a clinical research project?
It might be the chance to receive (better) treatment, or because your doctor recommended you to do so, or your personal aspiration to drive medical research for your indication.
In the end, the ultimate motif for participation may become irrelevant if you, as a patient, do not feel taken seriously, included, represented, involved or informed. Then, uncertainty or uneasiness (with regard to your health or data privacy!) quickly leads to discontinuation.
Put the patient in the center of every decision you make!
You want truly engaged patients for your study? Then put them in the center of every decision you make!
Your endpoints represent your patients’ preference; your study design goes hand in hand with the medical condition, medical care and life situation of your patients; and your study material takes your patients by the hand and informs them at every step of the project about what, when, how and why.
For successful patient engagement keep information high and live patient centricity throughout your study.
How? Let’s explore some approaches by having a closer look at 4 reasons why patient centricity is not just a buzz word.
1. The patient information is a comprehensive instruction manual customized for the patient
I will not give you a medical writing lecture or go into banalities like “Keep it short and simple”. Rather, I would like to shift the focus away from the “how” towards the “what”, i.e. the content of the patient information.
It is important to realize that the patient information is not just an obligatory document requested by the ethics committees. In contrast, it is a crucial study document when it comes to patient engagement and should be appreciated as a chance to get in contact with the patients and make them feel fully informed and certain about their decision for (or against) participation.
As such, the patient information also does not need to be written for the ethics committees (even if available templates are provided by them). It must be written for the patient!
It might seem like a triviality but still I would like to stress that the patient information should be customized for the patient.
While writing the patient information, be fully aware of critical details of your study like e.g.
the age of your patient population
restrictions of comprehension that might come with the medical condition of your patients,
the complexity of the therapy scheme or of the visits schedule in your study,
or the potential risks that your patients must be fully aware of.
On the one hand, language and vividness of the text must be adapted accordingly.
On the other hand, make sure that your patients can clearly follow the argumentation on why this study is performed, the design of the treatment scheme (placebo/ comparator/ investigational drug, frequency, etc.), the schedule of the medical visits, the performed examinations and questionnaires in use, and the potential benefit and risks that might come with the participation in the study.
Engagement and continuity only comes with full understanding and confidence in the procedure.
The patient information is not a report or procedure protocol simply listing what is done first, next, last. It is a well-structured, clearly phrased and comprehensibly argued instruction manual.
Do not hesitate to make use of illustrations, figures, and tables to support transparency and understanding for the patient. Even if the template you are using does not stipulate such “gimmicks” – the gimmicks may help your patient to understand the study and to adhere to a given regime.
After reading the document, there should be no questions left on the study process. Engagement and continuity only comes with full understanding and confidence in the procedure.
2. The choice of clinical endpoints matches the patient preference
The choice of endpoints must, of course, comply with regulatory guidelines. However, in addition to the regulatory accordance, the patients’ preferences and input should be incorporated.
When designing a clinical project and deciding for the clinical endpoints to be examined in a study, frequently the choice is based on the symptoms’ strength of the study indication. While this approach provides you with an organized list of potential endpoints sorted by the symptoms’ severity, the preference of the patient might fall behind.
That is, a rather predominant phenotype for the patient might not necessarily represent a regulatory-relevant endpoint.
A rather predominant phenotype for the patient might not necessarily represent a regulatory-relevant endpoint.
In contrast, a possibly easily measurable parameter must not coincidentally be an important measure for the patient. This might be particularly true for paraclinical measures like lab values or imaging results. Although the patient can be informed about and be aware of the importance of such a parameter, other conditions might be of greater impact for the patient.
Especially when side effects appear, the patient might revise his judgment on the relevance of certain measures in comparison to the then naturally much more important symptoms.
Thus, in order to come up with truly patient-relevant endpoints, I recommend considering the conduction of a patient preference study in the run-up of your (interventional) clinical project. This gives you the chance to get to know much better your patient population and its preferences upfront.
Why not ask the patients upfront if these values actually matter to them?
Once you are aware of the challenges and restrictions the patients are facing, you can plan your study accordingly. This applies not only to the choice of endpoints but to the study design in general.
This sounds trivial? Try to find a real evidence – not eminence (!) – based proof in the literature that lymphocyte count or splenomegaly represent relevant impacts on the patient with chronic lymphocytic leukemia. Not so easy, right?
So why not ask the patients upfront if these values actually matter to them? Or let’s rephrase the question: Wouldn’t you be more engaged in a study where you know that fellow patients have participated in the design and/or endpoint creation?
3. The study design is based on the patient’s condition with respect to indication, care and everyday life
In the same way as preferences and needs of the patient should lead your decision on study endpoints and patient information structure, they should also be in focus when it comes to the design of your study’s infrastructure, organization and schedule.
How does the medical condition influence the everyday life situation of the patient? What are the patient’s restrictions? What are his/her preferences and needs with respect to medical visits? Is the patient able to go down to a site or would it rather be suitable to think about transport services, visits at the general practitioner, home visits or a remote visit (site-less) approach?
Indeed, 55% percent of people rate the location of the site as the most decisive factor for/against the participation in a clinical trial1. Thus, a patient centered study-site-design can be of great benefit for study recruitment and continuation.
The basis for such new study designs – digital technologies, wearables, sensors and apps – do exist; also their acceptance and usage increases continuously.
Approaches like the so called “hybrid studies”, where patients have the choice between a classical site-visit and a remote visit via, for example, a digital platform, might incorporate the preferences of a much broader patient population and boost patient engagement.
The basis for such new study designs – digital technologies, wearables, sensors and apps – do exist; also their acceptance and usage increases continuously.
In Germany, for example, today 58 million people use the internet; 34.6 million of those are over 40 years old. Within the last three years, 4.4 million people over 50 years joined in. The number one device in use is the smartphone (66%)2.
Also healthcare apps and fitness trackers are on the up: in Germany, 28% of the internet users utilize such technologies on a daily basis, and of those only 31% are between 15 and 19 years while 30% are aged 60 years or older3.
Study designs that support the individual preferences will recruit and retain patients in the long run.
Thus, the widespread prejudice that digital technologies are only for the young patient population is simply wrong. I would rather argue for a personal preference, independent of age.
Thus, study designs that support the individual preferences and needs of the patient will recruit and retain patients in the long run.
But with all appreciation for the new technologies: please don’t use them with might and main just because they are trendy and hip. Always consider also the clinical routine and the usefulness of the application.
For example, using e-questionnaires on tablets at chemotherapy sites might sound fancy and reasonable in the first place. However, if certain sites don’t follow the protocol and patients are handed the tablets after receiving the treatment (that commonly coincides with a great discomfort), patient engagement might naturally equal zero and/or the patient reported outcome might simply give a wrong picture. A paper questionnaire that can be filled in at home or an e-questionnaire that can be filled in at home via a certified app might be a better solution.
4. Updates on the course of the study keep the patient informed
As a last reason why patient centricity is not just a buzz word, I would like to bring up the study material that is provided to the patient throughout the study. Thereby, it makes no difference whether this information is passed out by the physician at the sites or can be downloaded by the patient from a study platform or is sent to the patient via a mobile app onto his smart phone.
By providing the patient with regular updates on the study progress you show appreciation for his participation.
Also, by informing you can prevent the feeling of potential uncertainty about whether the study is still running, whether the patient’s data is of any use or value, whether the project is still on time et cetera.
Once your study has been completed, let the participants know about the next steps: What happens with their data? What is it used for? Will it be published? Of course there will be also interest in the results of the study. How can you make sure that the participants will get to know the outcomes of your project? Is it really sufficient “appreciation” to direct the patient to the EudraCT or clinicaltrials.gov, or could tailored information materials about the study also increase your visibility and image in the patient community?
The key to a successful study engagement lies in listening and a change in perspective: the ones’ who the study is designed for in the first place.
An empowered patient who feels involved, informed and at the center of your clinical project, will automatically be more engaged and, thus, increase the quality of your data and study results.
In my opinion, the key to a successful study engagement lies in listening (and patient centricity is just a synonym for it) and a change in perspective: the ones’ who the study is designed for in the first place.
Picture: @Jérôme Rommé /Fotolia.com
The electronic case report from (eCRF) played a pioneering role in the digitalization and introduction of ever new technologies into clinical research, and enjoys great popularity. Advantages like the availability of your data at all times, the rapid transfer of data also from external devices, automated alerting processes, predefined plausibility checks, and the possibility to use the EDC system as an information sharing platform, speak in favor of the eCRF within clinical and non-interventional studies.
Here, we would like to give you a short overview of how an eCRF develops in the course of a study.
1. The data management plan
At the very beginning of any data management involvement in the study, a data management plan is created in order to define the scope, standard operating procedures (SOPs), the respective templates and the responsibilities for data management procedures within a study.
2. The structure and data validation plan
The development of an eCRF itself starts with the final study protocol. As soon as the aim of the study and its contents are determined, the structure of the eCRF can be defined, i.e. the names and characteristics of all CRF items and corresponding database tables. For that purpose, a structure plan is created which is reviewed and approved – by all involved parties – before set-up and validation of the eCRF structure within the development environment of the EDC system.
Once the structure of the eCRF is finalized, the criteria for online and offline plausibility checks are defined. Additionally, conditions for E-mail alerts are specified (e.g. adverse event alerts, alerts if a patient is screened / randomized). Therefore, the finalized structure plan is amended with the data validation plan. Upon review and approval of the data validation plan by all involved parties, the implementation and validation of the online edit checks and E-mail alerts can be performed within the development environment of the EDC system.
To facilitate ongoing study and patient management, study-specific status reports are programmed and validated on demand (e.g. patient status by country, query report, adverse event listing).
4. Workflow definition
Apart from the structure and check criteria within the EDC system, it is important to define the project-specific EDC roles, their individual rights and workflows (e. g. who is allowed to enter / read / modify data, to raise / answer queries, to sign the eCRF).
For that purpose, the workflow definition document is created and, upon review and approval by all involved parties, the workflow is implemented and validated within the development environment of the EDC system.
5. User acceptance testing
Before Go-Live, the EDC system is tested for functionality and usability by test users who are, preferably, not familiar with the respective eCRF. The user acceptance test is an overall test to check if the eCRF fits its purpose. Therefore, all system components related to practice are tested (e.g. data entry, monitoring, query process).
Findings and comments have to be documented by each testing person within the user acceptance test report. These findings are reviewed and the intended solutions are documented within the user acceptance test report. Afterwards the corrections and changes are implemented in the EDC system and validated, if applicable.
6. Release of the EDC system / Go-Live
As a last step before Go-Live, once the EDC system is approved by all involved parties, the EDC system is transferred from the development environment to the productive environment.
7. User and access management
In order to get access to the productive environment of the EDC system, all users of the EDC system must be trained in handling the EDC system in their corresponding role. The training requirements are described in the data management plan.
Usually, also user manuals are created within the project-specific EDC system, in accordance with the different existing user roles (e.g. investigator, monitor). After review and approval by all involved parties, the manuals are handed out to the users of the EDC system. They may also be introduced to the users on the welcome page within the EDC system for download.
8. External electronic data – if applicable
Sometimes, external laboratory data or data from an electronic patient-reported outcome (ePRO) have to be incorporated within the eCRF. If study data are transmitted in electronic form from external data providers, project-specific details of external data transfer and import are described in the data management plan. The data transfer specifications (DTS) describe the content, structure and frequency of the external electronic study data transfers.
The DTS are created in collaboration with the external data provider before the first planned data transfer occurs. In order to check compliance with the DTS and technical feasibility, a test data transfer should be performed before the first planned data transfer. External data have to be imported into the study database either directly within the EDC system, or integrated within the exported database. If external data has to be imported directly within the EDC system, an interface has to be programmed and validated within the development environment of the EDC system.
In case of any questions on this subject, please do not hesitate to contact us! Our experienced data managers are happy to support you with the development of an eCRF tailored to your needs and the requirements of your study.
Your GKM Data Management Team
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