Assuring patient compliance to the study protocol-spending smart on monitoring

Today I want to go beyond having compelling ideas, a team and a great market opportunity and talk about what you need to successfully execute a clinical trial on your way to FDA approval.

Sometimes there is nothing more powerful than the passion and vision of an entrepreneur.

But passion and vision are just not enough. You need execution. You need to be able to accept the pain.

Execution for an early stage biomed startup means successful execution of clinical trials, from pilot through double-blind Phase I to Phase II and Phase IIB validating the efficacy and safety of your product.

Are you overly optimistic about the time it will take to get results from your study?

In our experience, even experienced entrepreneurs do not factor in the amount of time it really takes to collect data in the clinical trial and monitor and assure patient compliance.

Patient compliance to your protocol is by far the most important success factor for interventional trials. It is the basis for everything and the key to your time and money.

There are 2 schools of thought on the topic of assuring protocol compliance.

The first school of thought likes outsourcing everything to a CRO.

This is often an expensive proposition which does not assure optimising time to market for a very good reason: the CRO business model is not success-based.

The CRO business model is based on charging for professional services, not for delivering the statistical report in 6 weeks instead of 6 months. Your CRO does not price his services for a fast, successful delivery of data to statistical report or for guaranteeing recruitment.

The second school of thought is DIY – write your own protocol, develop your own eCRF and monitor your sites with contractors.

This is can be also be an expensive proposition which does not assure optimizing time to market because the sponsor will be cutting costs on monitoring and may get neck-deep into manual data extracts and data preparation in order to get the reports they need, working overtime to stay on top of the sites. Most EDC systems with their cookie-cutter data extracts are incapable of providing laser-accurate patient monitoring in an automated way. The default is to outsource the data extract, preparation and reporting to a bio-statistician – perhaps a CRO – which does not bring us any closer to shortening time to market.

So – let’s break this down.

There are 4 factors that can accelerate the time to statistical report in your clinical trial:

  1. Assuring patient compliance to the study protocol
  2. Assuring data quality
  3. Wasted time in clinical operations
  4. Increased clinician job satisfactions

1. Assuring patient compliance to the study protocol – when monitoring fails or succeeds

Patient compliance to your protocol is by far the most important success factor for interventional trials. It is the basis for everything and the key to your time and money.

Clinical trials are research studies that explore whether a medical strategy, treatment, or device is safe and effective for humans. These studies also may show which medical approaches work best for certain illnesses or groups of people. When a product is cleared by a regulatory agency such as FDA for marketing, the supporting evidence obtained from clinical trials becomes the basis for clinical practice guidelines, including a dosage of medication or proper intended use of a medical device.

Clinical trials are essentially scientific experiments that are monitored in order to assure the safety of subjects, compliance with the study protocol and collection of accurate data. There is a myriad of stakeholders involved in conducting a successful clinical trial process from life science companies, clinical investigators, investigative sites, study monitors, human subjects, nurses etc.
However, there are significant problems with monitoring that are related to slow detection of deviations, slow (or incorrect) response after detection of deviations, and general lack of reuse of knowledge and tools.

In this respect, the monitoring of patient compliance with the study protocol is particularly crucial because low compliance means more patients need to be recruited in order to achieve the required statistical power for the study. In paper-based clinical trials, response to deviations may take 2-4 months and in trials using electronic data collection, monitoring operations may respond to deviations in 5-8 weeks or more. Slow detection and response during the study push out the resolution of issues to the end of the trial resulting in an end-of-study “data cleaning” process which can take 6 months, delaying the statistical analysis, subsequent regulatory submission, and release of innovative treatment to market.

Further, slow detection and response to deviations increase costs. When a patient who is non-compliant is terminated out of a study, the time and money spent on the subject are lost and additional time and money is required to recruit a replacement.

2. Improving data quality
For data managers and monitors, nothing can slow clinical study speed (and increase study costs) like errant, unreliable, and/or ineligible data. Even something as trivial as penmanship can throw a monkey wrench into a study’s gears.

In the traditional method of paper data capture, a paper case report form (CRF) is used for collecting data and delivering it for review to a study monitor. There are myriads of problems that can happen along the way when using this method, everything from filling the CRF into the wrong location, skipping data fields, making errors in patient info, and so on and so forth.

Cloud EDC removes these errors almost entirely by using responsive online data validation. Since this is often a key factor in site CRC productivity – it is important to strike a middle ground between too many edit checks (which result in an inflation of queries) versus too little.

Before the software is implemented, the sponsor and vendor work together to create electronic case report forms (eCRFs) that are study-specific. While the eCRFs are being programmed, online data validation/edit checks assure valid date formats, data types and appropriate ranges before the form is saved.

This makes the job of data managers and monitors easier – when they know that the data in their hands is reliable and accurate. This also saves a tremendous amount of study time when less errors require monitors to go back and find the source of the error, because the data is sound in the first place.

3. Wasted time in clinical operations
If the most common search is for a phone number and takes you a few minutes to find a number, then in a clinical trial consider the time required to track down and monitor the hundreds of variables in a typical study database. Consider the time following discrepancy notes, doing SDV and reconciling data points reported by patients with data points in the EDC.

By using cloud EDC for clinical trials saves time when clinicians, data managers, monitors, and project managers have access to data at all times, and at any place.

The paper-based system of research data forces clinicians to keep data on-site, and then the data needs to be verified and entered into an electronic database. This takes twice the time, and as we mentioned before, puts your CRFs at risk.

When data is directly captured and entered into a laptop, tablet, etc. using EDC however, it is available for monitoring in real-time. This not only saves time in delivering the data for monitor review, but allows for remote access to data. Say, the project manager is at home having dinner. They get a notification on their smartphone that FDA regulations have changed. They can remotely access the EDC system and make compliance changes to the software before the study commences again the following day.

Time saved, costs saved, a day of hard work saved.

4. People who hate their job – your CRC is your best friend

For a sponsor, the most valuable resource is the CRC on site. If they are happy, well-compensated and well-managed and have good tools, they will do a good job.
Everyone works better when they know that they are doing their job well. Using cloud EDC with remote monitoring reduces work loads and increases satisfaction.

Project managers do not want their clinicians to become frustrated with errors, needing to repeat efforts and suffer the misery of redundant performance.

Because EDC is cloud based, study monitors can work remotely, saving on travel time and costs. According to a recent study, remote workers reported that 81% were happy with their job, versus 74% that worked on-site.

Clinical studies can go on for years, and during completion, if a clinician feels that they were satisfied while working with a team, they will be more willing to contribute their talents to a future study, saving executives and project managers time on searching for qualified talent.

EDC is win-win for managers and clinicians when everyone is satisfied with a job well done.

The 8th critical factor

VC investors consider some number (like 7 is a common choice) critical success factors for obtaining venture funding –

1. Compelling idea
2. Market opportunity,
3. Great team
4. Killer technology
5. Competitive advantage,
6. Credible financials
7. Validation

But there is an 8th critical factor for successful execution of clinical trials for a venture-funded biotech, biomed startup and that is time.

You can always raise more money, but you cannot raise more time.

You can shrink time and accelerate deliveries is by adopting automation of data collection and monitoring of patient compliance and site performance. This enables sponsors to be assure compliance and eliminate non-value people and paper processes (like 100% SDV) at the same time.

The latest in cloud technologies enables biotech, biomed executives to reduce their run-rate in a clinical trial, to reduce their burn-rate while processing the data and deliver the statistical report faster.