Introduction
Often ideas are generated but little is done on the follow-up to bring them to fruition. The purpose of this paper is to support the final stage of the Bow Tie Method- the management proposal.
This paper takes a general approach to:
- Build assumptions to quantify a clinical trial
- Characterize the average clinical trial for a company with 150 clinical trials
- Quantify the cost and savings for a group of 150 clinical trials. This approximates the project workload of a small to medium-size pharmaceutical or biotech company.
- Identify, quantify and calculate improvements projects
- Compare improvement projects to the status quo showing total costs and annual savings
The intent is to deliver an approach with a template that others can use and customize to their company. By using actual historical records and accounting data the reader can accurately characterize the clinical trials performed by their company. This will present a better picture of each of these improvement projects and highlight the comparison of alternative improvements.
Other important questions that should be asked but are not addressed in this paper are: Is the idea viable? How much does quality, service or cost improve? If it is a big gain for one part of the company does it really benefit the company as a whole? Are we making an improvement in one department only to penalize another department by shifting the burden?
Clinical Study and Group Worksheet- Assumptions and General Costs
The approach here is to quantify an average clinical trial (averaging across phase I, II, III & IV) and rolling-up to a group of 150 clinical trials that approximates the project workload of a small to medium-size pharma / biotech company. The resulting 150 average clinical trial group permits a simple calculation of total costs, comparisons and savings among several improvement projects.
Below is a map of France where a representative clinical trial with 800 subjects requiring a base of 3,000 doses would be conducted. The supplies would arrive from Edinburgh to 40 sites adjacent to airports noted below. The supplies in the worksheet do not require special handling. If special handling were required then distribution costs would be 3 to 4 times the estimated cost in the worksheets.
Clinical Study- Assumptions and General Costs
After the dynamics of a clinical trial are understood, then a systemicatic approach can begin. Assumptions become the base for the average clinical trial to deliver cost and key data for each alternative project. Below are the assumptions with operational conditions for the average clinical trial.
Once the baseline is established, the cost and key data of one average clinical trial multiplied by 150 delivers the group cost and key data. For example, the group of 150 clinical trials at status quo will cost a total of $35.6M to suppply the sites. Next, a company sizing exercise of the quantitative data for several ideas and improvement projects can be calculated and assessed accurately.
Below are calculations and savings for each project followed by comparisons of each scenario to the status quo for the group of 150 trials. The comparisons show the impact and savings specific to each improvement scenario versus the status quo.
Worksheets for a Clinical Study- Scenario A through E
All the scenarios share the same study characteristics: 40 sites, 800 subjects and a base inventory of 3,000 doses with the same sites inside France. Costs assumptions for unit costs and rates are the same for all scenarios. The status quo uses a base of 300 shipments and the other scenarios vary from this depending on the improvement(s).
Scenario A is Status Quo
Scenario A – Status Quo has:
- a shipping excursion(SE) of 12% w/ resupply of ½ all SEs,
- site temperature deviation (SD) of 10% w/ resupply of all SDs,
- a transportation failure of 1% that requires resupply of all failures,
- actual site recruitment is 90% of enrolled sites (This means 10% of all 40 sites that enrolled and received the initial stock will not have any subjects).
- Doses needed for the subjects for the study is a base of 3,000. This base does not include inventory load strategy that may create waste due to unbalanced enrollment, SEs, SDs, transportation failures or site enrollment inactivity.
- Other factors are considered to be void for this exercise.
Scenario B
Scenario B uses a new shipper that holds more supplies and delivers protection from damage and improves security. This scenario will:
- Implement reduction of 36 shipments from the status quo,
- reduce SE from 12% to 6% w/ resupply of ½ all SEs,
- training emphasis will reduce SD from 10% to 5% w/ resupply of all SDs,
- transportation failure is 0% because 2 hr back-up response is provided.
- actual site recruitment is 90% of enrolled sites (This means 10% of all 40 sites that enrolled and received the initial stock will not have any subjects).
- Doses needed for the subjects for the study is 3,000. This does not include inventory load strategy that may create waste due to unbalanced enrollment, SEs, SDs, transportation failures or site enrollment inactivity.
- Other factors are considered to be void for this exercise.
Scenario C
Scenario C uses new shipper that holds more supplies, protects from damage and improves security. This scenario will:
- Implement reduction of 36 shipments from the status quo,
- reduced SE from 12% to 2% w/ resupply of ½ all SEs, training part of existing program
- SD stays at 5% w/ resupply of all SDs,
- transportation failure resupply is 0 because back-up transportation w/ 2 hr response is provided,
- actual site recruitment is 90% of enrolled sites (This means 10% of all 40 sites that enrolled and received the initial stock will not have any subjects).
- Doses needed for the subjects for the study is 3,000. This does not include inventory load strategy that may create waste due to unbalanced enrollment, SEs, SDs, transportation failures or site enrollment inactivity.
- Other factors are considered to be void for this exercise.
Scenario D
Scenario D uses larger new shipper allowing orders to reduce the number of shipments.
This scenario will:
- Implement reduction of 72 shipments from the status quo,
- reduce SE from 12% to 2% w/ resupply of ½ all SEs,
- SD stays at 5% w/ resupply of all SDs,
- transportation failure resupply is 0 because back-up transportation w/ 2 hr response is provided,
- actual site recruitment is 90% of enrolled sites (This means 10% of all 40 sites that enrolled and received the initial stock will not have any subjects).
- Doses needed for the subjects for the study is 3,000. This does not include inventory load strategy that may create waste due to unbalanced enrollment, SEs, SDs, transportation failures or site enrollment inactivity.
- Other factors are considered to be void for this exercise.
Scenario E
Scenario E uses a larger new shipper that holds more doses while protecting from damage and improves security. The larger shipper allows 48 shipments of all the site supply requirements with the minimum number of shipments. The project will purchase secure cabinets or refrigerators / freezers for each of the 40 sites. This scenario will:
- deliver 54 shipments to 40 sites with initial stock and resupply shipments.
- SE at 2% w/ resupply of ½ all SEs,
- SD at 2% w/ resupply of all SDs, due to new cabinaets/ refrigerators, etc.
- transportation failure resupply is 0 because w/ 2hr back-up response is provided,
- actual site recruitment is 90% of enrolled sites. This means 10% of all 40 sites that enrolled (idle) and received the initial stock but not have any subjects.
- Doses needed for the subjects for the study is 3,000. This does not include inventory load strategy that may create waste due to unbalanced enrollment, SEs, SDs, transportation failures or site enrollment inactivity.
- Other factors are considered to be void for this exercise.
Summary Comparison of Scenarios that are Company-sized
Comparisons of Scenario A to Scenario B
Comparisons of Scenario A to Scenario C and D
Comparisons of Scenario A to Scenario E
Discussion of Scenario E
PRO: The system is handling 54 (ideally 40) shipments, significantly reducing documentation and import/export activity and transaction fees. The status quo has 329 shipments. The distribution portion of the pipeline is smaller with a shorter timeframe. This leads to a better quality results if for no reason other than the lower exposure rate. Emergencies at site will need future attention and should be planned as matter of risk mitigation but are well within existing resources. Significant quality benefits and savings.
CON: Site enrollment may exceed inventory sent for initial stock. This may require more supplies approximating quantities in Scenario C . This will initially require a lot of training and coordination with clinical site intitiation teams. Beforehand, there must be an approach agreed with the tax, accounting, to address a perceived conflict of interest for giving or loaning the sites the cabinets / refrigerators. The cost savings and handling benefits far outweigh even higher costs to purchase and administer these cabinets, refrigerators or freezers. Long term strategy could deliver 2nd or 3rd study at same site with no cost of cabinets because they are already installed from the earlier study.
Summary of Results
The Next Step
The final comparisons and discussions are next used to make recommendations to management or a decision-making group to either provide support for a scenario or to not move forward.
As noted in the beginning, the intent of this supplement was to show that modeling for an average clinical trial. This model must condsider many details and assumptions of the clinical trial activity and costs unique to the sponsor’s methods. The approach and template is intended to give the reader a way to move an idea(s) forward through the planning stages and turn it into an actual improvement project in their company.
Note:
1This is a supplement to the article “ What Happened on the Way to the Customer “ Journal of Pharmaceutical & Biopharmaceutical Contract Services, May/June, Vol 13 Issue 3 by Ray Goff.