There is an exciting paradigm shift happening in industry sponsored clinical trials, particularly for the patients contributing to research. Prior to joining Koneksa I worked for one of the highest enrolling clinical ophthalmology sites in the country, where over 25 studies were conducted at a time. I’ve experienced first-hand the significant burden placed on participants in clinical trials, with study visits lasting well over six hours. From the inefficiency of paper-based trials, I am in disbelief of how seamlessly the Koneksa Compare functions and how simple it is to administer questionnaires and promote protocol adherence with reminders. Working at Koneksa has shown me just how functional trials can operate.
I will share my experiences as a coordinator where, on many occasions, I (and patients) were met with difficulty.
This includes waiting room shuffling due to a standard order of assessments such as fasting blood draws. At a large site, a research participant could be waiting two hours to complete the detailed protocol tests. The lag times are worsened by the strict order for completing assessments. Coordinators must complete certain tasks at specified times and record the entire process on packets of source documents. I recall many phase two protocols requiring morning blood draws with laboratory tests, urine analysis and visual acuity testing - all before nine o’clock in the morning. Although compensated for their time, participating in trials is challenging for most working-class people and cumbersome for older persons to energize through tiring tests, long questionnaires, and stacks of amendments of informed consent forms to sign.
As a clinical trials coordinator, facilitating a pleasant patient experience was challenging due to the volume of study patients as well as multitude of assessments to conduct. Some trials were double-blinded, and others were open-label but each member of the research staff played different roles. For instance, one physician was the Principal Investigator for one study but the unmasked sub-investigator for another. Only signatures of certain Investigators were allowed on certain unmasked source documents. To add to the confusion, once study participants completed one study they entered a general washout period and were screened for other similar diagnosis studies. Patients had difficulty complying to the more complex protocols which required paper pain/medication diaries in addition to daily intravenous injections for uveitis. There were different methods to assess visual acuity and different definitions of eye terms for each electronic case report form. These non-standardized methods translated into clinic days where 10 patients were facilitated through 10 diagnostic tests, yet all capturing essentially the same metric. As a coordinator, I would attempt to maximize the patients’ time by having them fill out the ICFs and quality of life questionnaires while waiting to see the physician. The patients often grew tiresome of the long forms and diary questions but all I could offer was my sincere apologies and water.
My experience working with ophthalmology studies included managing patients through invasive tests such as optical coherence tomography and imaging of the eye with fluorescein angiography to visualize blood flow in the retina and choroid. The injection of the dye was an additional “poke” which the patients had to endure after their first blood draw to satisfy imaging requirements of the sponsor. The laundry list of visit examinations to complete was exhaustive and seemed unnecessary at times, especially for geographic atrophy, a dry end-stage macular degeneration. Protocols from the major pharmaceutical companies included at least four different types of imaging of the eye in addition to triplicate ECGs. When the Principal Investigator met with the patient, I noticed they only looked at one relevant picture of the eye and disregarded all other test results.
The way the questionnaires were administered seemed inefficient as well. One quality of life questionnaire was fourteen pages long and required writing with an attached carbon copy. This feature caused problems because the surfaces where the patients took the questionnaire would carry through the second copy, and often times with odd lines and scribbles. It was often hard to detect the exact time when the questionnaire was taken. Once the coordinator collected the questionnaires, each page copy had to be torn apart and placed into two separate study binders. I found it odd that the EDC (electronic data capture) did not ask for the responses to the questionnaires but asked whether the patient had taken it or not. This led to using three different applications for the data entry of one questionnaire.
My fellow coordinators and I would dread certain study visits where three questionnaires were administered because the resulting paperwork would be exponentially longer.
To encourage patient compliance and adherence to attend all study visits, coordinators would call patients two times a week to confirm their attendance. If this was not done in the acceptable window of time mandated by the study, the site would incur protocol deviations. Some evenings after the last patient left, I would file five protocol deviation reports to the independent ethics committee. The precision, accuracy, and tenacity of clinical trials is often placed on the study coordinator who is responsible for liaising the trial and communicating all messages to sponsors, sites, and IRBs. Together with the medical monitor, ensuring protocol adherence is paramount to establish drug efficacy but is often beyond the realistic capacity for patients to undergo.
Patients frequently expressed anger and confusion as to why so many assessments were recorded at one visit. Although the coordinator would read, explain and have the patients sign each page of the ICF, it seemed forgotten as soon as the reality of the study procedures set in. Setting expectations for the patients was essential because certain visits would be longer and busier, while others would be shorter. Despite setting expectations, patients expressed how their opinions, feelings, functional ability, and input did not matter, which resulted in some patients’ early termination from the studies. The study lacked an outlet to consider the patient’s experiences or measures.
In this strenuous clinical trials atmosphere, the vital experience of patients must be considered and appropriately captured. Patient safety in terms of empirical clinical data should be supplemented with electronic patient-reported outcomes. It is crucial to get direct symptomatic input from the patients regarding their health status during the development of drugs. In cases where clinical outcomes such as breathlessness, neuropathic pain, and sleep disturbances are experienced outside of the clinic, obtaining symptomatic data regarding the unobservable events is best taken from the patient directly. By launching a validated ePRO during certain phases of the study or selecting current pain level after taking study drug are fundamental to capturing the full progression of the relationship of the study drug to the disease.
The largest pharmaceutical companies have already integrated different means of collecting patient-reported outcomes such as questionnaires about mental health status or side effects of a disease on a patients’ quality of life. The ubiquity of internet access and smartphone capabilities has launched a valuable interconnectedness between real-time data collection from ePROs/eCOAs such as a weekly smartphone administration of WHO QOL questionnaire or a visual analogue scale to assess post-dose pain severity. The possibility to collect patient-reported data is limitless and becoming extremely relevant in endpoint selection. EPROs would greatly increase efficiency for coordinators and lead to a better experience for all involved entities.
It is all too easy to focus solely on primary objectives to establish safety, tolerability, and efficacy of an investigational new drug but the ability to detect change (endpoints) in terms of electronic patient-reported outcomes such as 30% pain score reduction strengthens the holistic approach of clinical trials for the patients and investigators. Remaining cognizant of what degree of environmental factors affect the patient may lead to applications of ePROs which analyze continuity of care through annual health-related quality of life questionnaires and thus, fortify follow-up in an innovative way.
From the FDA’s guidance for Industry Patient Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims,1 clinical trials can be designed from PROs with strong theoretical framework and construct validity to effectively capture health inclinations from the patients directly. This is instrumental in current times as biotechnology and wearable’s are dominating the market. Koneksa Health follows this guidance document and integrates highly validated ePROs/eCOAs in clinical trials. Our software is equipped to create electronic versions of questionnaires to communicate this perspective at any desired time interval. The unity of patient-centered health research through ePROs/eCOAs will steer the focus of clinical trials back in the patient’s hands.
1. US Department of Health and Human Services (USDHHS) Guidance for industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. 2009 December; www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/UCM193282.pdf
By Janhvi Patel, Clinical Operations Associate at Koneksa Health