All preclinical study estimates are not created equal. What common costs in preclinical research you should expect, and what should you watch out for, in your next preclinical study?
Preclinical studies can be expensive. Medical product innovators need to know much more goes into the making of a high quality, value-based preclinical study that is critical, but not always obvious. A high quality product providing data from a preclinical study and the associated final report are of high value in the medical product lifecycle.
Here are some of the most common cost types you should consider when planning your preclinical study to give your product the best chance of getting to market as swiftly and efficiently as possible focusing on what matters most – clearance from regulatory bodies like the FDA.
1. Protocol writing
Preclinical studies (non-GLP and GLP) require a detailed protocol that is reviewed and approved by IACUC, the Institutional Animal Care and Use Committee. Study directors and principal investigators (PIs) spend a considerable amount of time writing these protocols which dictate the conduct of the study and eventual data-based results and reports. While preclinical study protocols share some commonality, they are customized for every product and every study. Preclinical protocol writers bear responsibility for the difficult task of translating a small study synopsis into a detailed protocol. Despite the presence of predicates, protocols or estimates from other CROs or consultants, protocols are typically written in accordance with the standard operating procedures from the CRO you engage to execute the study. Those standard operating procedures may vary considerably
2. Animal / model acquisition
A good preclinical CRO will purchase models from a purpose-bred USDA approved vendor designated as “Class A” or “Class B.” A healthy model from a trusted vendor is key to the success of a preclinical study. Therefore, it is the best investment you can make. Acquisition costs for your models include quarantine of the animal, vaccinations, USDA health records, transportation and initial health inspections. Costs vary based on the number of models and the number of shipments needed. For example, if you decide to do a study with three models now and three models six months later, you will incur two separate transportation costs.
3. Procedural costs
The procedural costs take into consideration the length of the procedure and the requisite staff, facilities, equipment and supplies needed to perform the procedures based on the scope of work.
Breaking these down further, costs increase as the more “bells and whistles” are added to the procedure. For example: an open chest bypass surgery requires an exhaustive amount of supplies and specialized staff including: anesthesia, bypass supplies, perfusionists, surgeons, and other skilled staff compared to a quick interventional study that may only require a sheath, catheter and fluoroscope.
Planning these studies is no different than a patient undergoing a surgical procedure at a hospital because the same exact supplies in the same exact setting are being used for the execution of these procedures in a sterile fashion.
Highly skilled is another important component of the procedure cost. Whether you are bringing your own surgeon or the preclinical CRO is providing the surgeon you must pay for their expertise. Is there a study director and PI involved in the procedure? Are there veterinary technicians or veterinarians involved? Those considerations or requirements determine procedure cost.
Depending on your procedure you may require a wide array of equipment including, but not limited to: cath lab, ultrasound and endoscopes. Again, the equipment requirements are as they would be in a human surgical procedure. The CRO shoulders the burden that ensures these pieces of equipment are in compliance with the federal code of regulations as well as the maintenance and calibration records to ensure GLP compliance.
Oftentimes there are several procedures for a single preclinical study. For example: there is an initial procedure, commonly an implantation. There may be a follow up procedure like a simple imaging study. The number of added procedures increases the overall cost. You must also consider whether or not these must be done in a sedated or anesthetized model because they increase the number of supplies and personnel involved. Keep in mind procedures must be conducted in consideration of animal welfare regulations. There is no compromising on the supplies, equipment and personnel needed to ensure animal welfare.
These are daily charges per model per day paid during the survival period. Per diems include: standard observations, husbandry and standard medications, food and water. The longer your study, the higher the per diems. If, for whatever reason, your study stalls or you have the animals waiting between procedures, you must pay the per diems for those days.
4. Observations / tests / follow ups
The procedural portion of a preclinical study does not end with an implantation. Post-implantation care is required. Depending on the objectives of the study, there is a significant amount of data collected during the survival period. Keep in mind the type of data collected during the survival period may be influenced by the expectations of a regulatory body. Some of the common costs during survival period are as follows:
- SOAP examinations are special exams known as “subjective, objective assessment plan.” They are conducted by a qualified veterinarian or veterinary technician. A quality CRO will always recommend these and include them in a GLP preclinical study. These observations may include neurological exams, body assessments and gait assessments. The frequency and length of these exams influences cost.
- Clinical pathology like blood or urine tests drive cost as well. A good preclinical study, especially GLP, includes baseline pre-op, post-op, follow up and terminal blood work. The number of tests conducted and where will influence the costs – for example, a CBC test is much cheaper than a biomarker analysis.
- Follow up – Whether it is a sensor reading, cage-side ultrasound or other test, follow up tests add time and personnel which influences cost.
Supplies include everything from medication to sutures. There are some standard medications “baked in” like standard pain medication or antibiotics. However, just like clinical cases, there may be specific medication needs. Your study may require Aspirin and Plavix for the duration of the study, a special anticoagulation drug, or there is an adverse event that requires additional medication(s). Sometimes there are many supplies needed for the initial procedure as well. Many supplies are considered standard, others are considered speciality like stents, catheters, special guide wires, etc.
Another important consideration for supplies are predicate devices. Are you expecting the vendor to obtain the predicate device? Predicates aren’t always easy to acquire, require special vendor agreements and therefore can get expensive very quickly.
A high quality comprehensive report requires expertise and time. While some investigators may simply want data for the publications coming out of their lab, often a full report from an independent lab is better for regulatory submission. When required, a reputable preclinical CRO will deliver a comprehensive preclinical final report. This is where it becomes abundantly clear that you get what you pay for. Do you want a comprehensive report that does not generate any questions from a regulatory body? Do you want just a transfer of data and tables that will require additional processing before it would be ready for publication or submission?
Our final reports for GLP studies include the incorporation of veterinary reports, necropsy reports, histopathology reports, pathology reports and any other contributing scientist reports. Clearly, a one-thousand page report will cost more than a 200 page report. Its value, however, lies in the need and appreciation regulatory reviewers place in a comprehensive, easily reviewable preclinical report completed by an independent and experienced team. Our relationships with regulatory bodies including the FDA helps guide how we put our reports together.
7. Third party vendors
The culmination of a preclinical study is often histopathology or toxicology. Is the CRO you engaged doing that work themselves or are they outsourcing to third party vendors? A good CRO will always recommend the highest quality third party vendor and will not compromise on quality from that vendor.
8. GLP charges
For a GLP study, most CROs add a GLP surcharge. This charge exists for very good reasons. It helps to cover the vast amount of regulatory and compliance work that mostly takes place behind the scenes. Visibly, this includes quality control personnel who audit all study data in real time, from the implant procedure to the explant procedure and everything in between. But the surcharge also includes data verification, archiving and equipment maintenance and calibration, creating and maintaining SOPs, as well as creating and maintaining training records. Quality assurance team members spend countless hours auditing data. The GLP fee ensures this is conducted.
Look out for hidden costs
We are often presented with preclinical study estimates from competitive CROs that appear to be far less expensive on the bottom line than what we provided. Don’t be misled by a preclinical study estimate. When we dive into the details, we often find it is not an apples to apples comparison. For example: overages in the operating room. If you budgeted for a 3 hour procedure and it runs 5 hours, are you seeing those costs or not? If you have added personnel, does the estimate include associated charges for supplies? An estimate should be all encompassing. The cost estimate should be very close to the total final cost when all invoices for services, supplies, etc., are ultimately reconciled and billed.
It is not a realistic expectation to have a preclinical study estimate fit a predefined, finite dollar amount. Be sure to do your homework by getting estimates from multiple CROs so that you can budget for the right amount of money for preclinical work.
We can’t stress enough what our decades of experience in preclinical work has shown us: the most expensive preclinical study is the one you have to repeat. Too many times we see sponsors who come to us after having chosen not to do a pilot study or compromised on the end points or amount of data collected during a GLP study elsewhere; eventually having to repeat it. This not only doubles the expenditure on preclinical work, it will consume a large amount of time, which can be as important as the monetary costs – not to mention the potential damage to investor and manager confidence in your decision making.
If you are evaluating your medical product’s readiness for preclinical, or if your GLP study conducted by another CRO has raised questions, we are here for you. Let’s talk. Contact us via the form below.