Clinical Trials for Medical Device Innovators Part IV: Cost Drivers for Clinical Trials

clinical-blog-2The fourth, in a blog series about clinical trials for medical device innovators. Read part I: Designing Clinical Trials, part II: Regulatory Considerations for Clinical Studies, and Part III: Managing Clinical Trials, here.

There is no denying that clinical trials are expensive propositions. There is little economy of scale; by and large, big pivotal trials cost proportionally more than small studies. The best thing one can do is design the study well to collect only the most relevant data, size it properly based on solid statistical grounds, select investigative sites judiciously to provide sufficient numbers of subjects, and manage the trial efficiently. These actions will not make a study inexpensive, but emphasis on consistency and paying strict attention to all the details will help minimize the cost. The cost drivers for clinical studies are numerous, vary between studies, and are certainly subject to change over time. Rather than attempt to attach a current monetary value to each cost driver, it may be as valuable to provide a list of these drivers so that you, as the study sponsor, understand what estimates you will need to price the study. The following is a list of items that must be considered when estimating the cost of a clinical trial:

  • Starting up one investigative site:
    • Contract costs
    • IRB review (at each site or single central IRB?)
    • Site screening visit (if necessary)
    • Site initiation visit
    • Initial device inventory
  • Data management:
    • Creation of a database
    • Creation of a data collection system [typically electronic data collection (EDC)]
    • Training site personnel on data entry
  • Data collection:
    • Reimbursements to site for completed data forms (typically at patient screening, procedure, and follow-up; priced per form completed)
    • Reimbursement to site for tests and procedures that are not “standard of care” for the disease entity or procedure compensation to patients for travel and parking if nontrivial
    • Data review and queries
  • Project management:
    • Monitoring visits (interim visits [how many?], final closeout visit)
    • Establish or contract with a Clinical Events Committee (if needed)
    • How many meetings over course of study?
    • Establish or contract with a Data Safety Monitoring Board (if needed)
    • How many meetings over course of study?
    • Contract with core laboratories, for example, imaging (if needed)
    • Final data analysis (statistician) and preparation of the manuscript

Regulatory costs for conducting clinical studies are minimal. You may have the cost of a meeting with FDA if you decide to have a pre-IDE meeting; however, these meetings can be held by teleconference. There is no fee to submit the IDE application itself. The primary regulatory costs come when applying for market approval. If your device requires a 510(k) application, the fee is $4690 (USD 2017). For a premarket approval application (PMA) for a Class III device, the fee is $234,495 (USD 2017). If you qualify as a small business, the 2017 application fees for a 510(k) and PMA are $2345 and $58,624, respectively.

Small businesses with an approved small business designation are eligible to have the fee waived on their first PMA.

Clinical trials are exciting, exhausting, and expensive. As an innovator of a new medical device, you need to decide what role you want to play in the life cycle of your device (concept to commercialization). Do you want to give it up for adoption (sell the IP early), or do you want to try to raise it to adulthood (obtain full regulatory approval to market), or do you want to participate in something in between? That answer will help you decide if you need to conduct a clinical study on your device and if so, the type of study. Do not go into a clinical study lightly! You have an obligation to your subjects/patients to run the best possible study. They deserve to have their contribution count. Regulatory authorities demand accurate, truthful, and complete data. You must demand the same. After all, it is your reputation and that of your device on the line.

For more information, please visit our website at https://medinstitute.com/.

Continue to follow our blog to view the upcoming Part V: Important Points.

Clinical Trials for Medical Device Innovators Part III: Managing Clinical Trials

5 tipsThe third, in a blog series about clinical trials for medical device innovators. Read part I: Designing Clinical Trials and part II: Regulatory Considerations for Clinical Studies, here.

Except for small, clinical feasibility studies, unless you are an experienced clinical trialist, do not try to manage a clinical trial on your own. The larger the trial, the more help you will need. Hiring a contract research organization (CRO) to manage the trial may be your best, or only, option, but be prepared for the expense. Similarly, if FDA submissions are needed, you may be wise to seek the help of seasoned regulatory affairs professionals.

Conducting a clinical trial entails a lot of individual tasks. Your study design will have determined the number of patients you need to enroll. How many investigative sites will you need? This decision involves a trade-off between cost and speed of enrollment. Each site costs on the order of $75,000 (2017 USD) to bring up. You may wish to set a minimum number of patients to be enrolled per site, but that is no guarantee that each site will come through for you. Select sites judiciously, which may require on-site screening visits. Be careful, because the inclusion of a site that enrolls no, or only 1 or 2, patients is expensive and demoralizing. Remember, you will need a contract with each site, and each site will need local IRB (Institutional Review Board) review and approval unless you have contracted with a central IRB to oversee the entire study. Currently each IRB submission also usually costs money. You will need to perform an initial site visit, often with some level of training on the protocol and data entry for the investigators and the personnel who will actually be doing the study and collecting the data. Interim monitoring visits are required to ensure compliance with the protocol and to compare source data with data entered in the database according to a predetermined monitoring plan. Closeout visits are also needed at the end of a trial. As data come in, it is rarely perfect. Someone will be needed to review incoming data and prepare queries to the sites as necessary; we cannot stress how important this activity is to ensure the integrity and quality of the data.

Larger, more complex, multicenter clinical trials may also require (or benefit from) one or more of the following management tools.

Clinical Events Committee (CEC)

A group of unbiased physicians knowledgeable in the field of interest, typically charged with adjudicating whether or not individual serious adverse events (SAEs) are related to the use of the device or to the procedure under study.

Data Safety Monitoring Board (DSMB)

A group of unbiased physicians not involved in the trial but knowledgeable in the area. They are charged with developing rules for halting the trial based on anticipated aggregate rates of SAEs.

Core Laboratory

A central laboratory set up to provide unbiased analysis of specific results (e.g., imaging, measurements, or analysis of all clinical specimens); such a laboratory provides consistency in the analyses. Smaller studies, particularly early feasibility trials, will need this level of oversight only rarely.

ANALYZING THE RESULTS

Once again, smaller trials or observational studies that are simply reporting means and standard deviations and perhaps simple t-tests for comparisons may not require an independent biostatistician. In contrast, more complicated studies requiring complicated statistical analyses, studies with multiple endpoints, and studies requiring computational modeling, are all likely to need a biostatistician with particular expertise in the analysis of complex study designs.

For more information, please visit our website at https://medinstitute.com/.

Continue to follow our blog to view the upcoming Part IV: Cost Drivers for Clinical Trials.