Financial impact of the hospital pharmacy’s participation in clinical trials

Abstract

Objectives

To estimate the cost of the hospital pharmacy’s participation in clinical trials (CTs) and to compare it to the amount received in compensation from sponsors.

To analyse the financial impact of CTs that end without recruiting any patients and without any financial compensation from promoters.

Methods

This retrospective observational study analysed data from 5 years (2014–2018) at a tertiary university hospital.

We established an allocation formula taking into account direct costs related to the pharmacy department’s CT area’s activity (reception, safekeeping, preparation, devolution, and destruction of medication, as well as patient monitoring) and indirect costs (facilities, resources, support staff). We calculated the costs to the department and the compensation received both overall and based on the type of promoter, clinical department involved in the trial, and the number of patients included.

Results

We included 134 trials. Costs added up to €207 372.95 and the compensation to €149 128.93 (€58 244.02 loss for the department). Trials ending without recruiting patients (33.6%) and without compensation accounted for 57.45% of the deficit. The mean cost of trials ending without recruiting patients was €875. We plan to charge a reimbursable setup fee for opening CTs to safeguard against these losses (€875 for trials in all departments except oncology; €1100 for oncology because 38% of their trials end without recruiting patients) and to compensate for the costs incurred in participating in trials for cooperative groups without financial compensation (20%).

Conclusions

Billing sponsors based on costs incurred for each trial would be a fairer system than the current approach based on the number of patients included. Establishing an initial fee would make up for losses from trials that fail to recruit any patients.

Introduction

Clinical research is essential. It helps us face the challenges of the future by generating scientific knowledge and driving innovation in preventing and treating disease.¹

Clinical trials (CTs) evaluating drugs are carried out mainly in hospitals, and the sponsors of the trial must assume the costs of the entire process. In this setting, both the pharmacist and the pharmacy department at the investigational site play a crucial role in ensuring that the CT is carried out correctly.² According to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (ICH E6), the pharmacist can be designated by the investigator or institution the following tasks:

• Accountability of the investigational medicinal product (IMP).

• Maintenance of records of the IMP delivery to the trial site, the inventory at the site, the use by each subject, and the disposition of unused product(s).

• Storage of the IMP as specified by the sponsor and following applicable regulatory requirements.

• Ensure that IMPs are used only in accordance with the approved protocol.

• Explaining the correct use of the IMP to subjects and healthcare professionals at appropriate intervals.

To fulfil these responsibilities, the pharmacy at the CT site must have the adequate infrastructure allowing it to maintain restricted access to the IMP and the randomisation codes (when applicable), an appropriate separation and differentiation between the IMP and the rest of the medication, and adequate control of the temperature and other environmental factors to ensure the conservation of the IMP according to the sponsor’s specifications.

It would be reasonable to assume that participating in a CT could result in significant savings in hospitals’ medication budgets because hospitals do not pay for the drugs.^3–8 Nevertheless, data are lacking about the economic impact of participating in CTs on hospital pharmacy departments, which must participate in any clinical research involving medication.

The sponsor must compensate the centre for the expenses derived from the performance of the CT, and the exact amount is settled on an agreement signed by the sponsor and the research foundation. At our centre, the pharmacy department receives a percentage of the budget for each patient included in a CT as compensation for the tasks performed. During the last decades, the research foundation and the hospital have set up agreements on how the budget should be distributed among the departments providing support to the CT. It has been agreed that if the pharmacy department must manage the receipt, control, storage, dispensing, and return of the IMP, the fee is 5% if the department does not have to manipulate the IMP (mainly reconstitution), 10% if the department has to manipulate it, and 15% if the department has to mask the product, fill out case report forms and/or perform tasks outside the usual workflow. The pharmacy normally receives no compensation when the sponsor of the study is a non-profit organisation such a research institute or a cooperative group (non-commercial sponsor) as in such cases the centre receives no financial compensation at all. It is important to point out that the centre’s research foundation deducts 25% of all payments received by the institution under structural costs (such as administrative managing of the trial), so the above percentages are calculated after this amount is subtracted, not from the total amount that the sponsor pays the centre. Thus, the pharmacy department receives 3.75%, 7.5% or 11.25% of the amount that the sponsor pays for each patient included. This system is used by most hospitals in Spain. If the centre does not include any patients and therefore does not receive any payment, the pharmacy department receives no compensation. We consider that a system in which the sponsor compensates the pharmacy department based on the activity it carries out in each CT would be fairer and more sustainable than the current system based on a percentage for each patient included in the study.

Objectives

To evaluate the financial impact for the pharmacy department of the participation in a CT under the current system of compensation based on a percentage of the total budget.

To estimate the costs of the participation of the pharmacy department in CTs (including reception, storage, reconstitution, and return and destruction of the IMP as well as keeping traceability records).

To analyse the economic impact of participation in CTs for which the department is not compensated because eventually no patients are included.

Methods

This retrospective observational study analysed data from our pharmacy department’s participation in CTs with medicinal products. All CTs initiated at our university hospital between 2014 and 2018 and finalised before 31 December 2019 which required the participation of the pharmacy department were included.

We came up with a formula for estimating the costs derived from the pharmacy department’s activity related to participation in CTs, including the direct costs related to the activities carried out in the trial as well as the overhead costs related to supporting staff and the use and maintenance of facilities and resources in the clinical trial area (CTA).

The direct costs were calculated based on the time professionals spent on tasks related to reception, storage, reconstitution, returns and destruction of IMP, as well as monitoring patients (initial and follow-up visits, audits and closure) and the cost (per hour) of staff (CTA pharmacist and technician) involved in carrying the activity.

To calculate general costs, our analytical accounting department catalogued the CTA facilities and determined the annual cost of the infrastructures (electricity, computers and maintenance, telephone lines, cleaning service, office maintenance and custody warehouse of clinical samples, proportional cost of maintenance structure of the building) and cost of storing samples at room temperature or refrigerated (maintenance and certification of temperature recording probes, maintenance of refrigerators and freezers, and so on).

Each CT was assigned a cost according to the activities performed.

Information about the payments the pharmacy department received for each CT was extracted from the invoicing system for CTs of the research foundation.

Results

A total of 134 CTs were included for the analysis of costs.

Figure 1 shows the estimated costs of the different concepts in the CTA budget outlined in the Methods section.

Figure 1.

Costs defined for aspects involved in the budget for the pharmacy department’s clinical trial area.

Figure 2 shows the distribution of the CTs according to the clinical departments involved; in 90 (67%) trials the fee for the pharmacy department was 5%, in 8 (6%) the fee was 10%, and in 32 (24%) it was 15%. In 4 (3%) studies there was no compensation. This distribution was different for oncology and haematology, where most CTs had a 15% fee (73.3% and 66.7% for oncology and haematology, respectively).

Figure 2.

Number of clinical trials by department and pharmacy fee.

In 45 CTs, no patients were enrolled and therefore the pharmacy department received no financial compensation. Table 1 shows the direct and overhead costs assigned according to the task performed by the pharmacy department and the actual amount received for the 134 CTs included. The total cost assigned to the activities carried out by the pharmacy department concerning the CTs included in the study was €207 372.95 and the total amount the pharmacy department received from the sponsors was €149,128.93; thus, the balance was negative (€58,244.02). The CTA’s infrastructure (overhead costs) accounted for 57.5% (€119 241.45) of the costs, activities related to handling the medication accounted for 25% (€51 776.75) and activity related to monitoring the trial accounted for 17.5% (€36 354.95).

Table 1.

Summary of the activities performed by the pharmacy department related to the included studies (n=134) and its calculated costs

Pharmacy departments’ activity	Total (n)	%
Trials requiring preparation	39	29.10
Trials requiring masking of drugs	14	10.45
Trials requiring control of medications returned by patients	60	44.78	Cost of the facilities
Trials with refrigerated storage	76	56.72	Refrigerator	€13 793.99
Trials with controlled room temperature storage	95	70.90	Controlled room temperature	€2 391.69
Trials with refrigerated + controlled room temperature storage	40	29.85
Mean trial duration (days)		726.90	Other infrastructure	€103 055.77
Description of activities related to the handling of IMP				Cost of the activity
Deliveries received	1245	Kits received (n)	15 484	€4668.75
Deliveries with reusable Crēdo™ containers	92			€138.00
Dispensations	7411			€25 938.50
Preparations	1857			€15 784.50
Medications returned by patients	3246			€3246.00
Devolutions of medication to sponsors	145	Kits returned (n)	4442	€705.00
Local destruction of medication	94	Kits destroyed (n)	4020	€1296.00
Description of monitoring activity
Type of visit	Visits done (n)	Time registered (min)	Time (hours)	Cost of the activity
Initial visits	132	6670	111.17	€10 244.77
Follow-up visits	586	69 755	662.58	€19 302.78
Quality control/auditing visits	14	1480	24.67	€3326.27
Closing visits	121	6710	111.83	€3481.13
			Total cost	€207 372.95
			Total received from the sponsors	€149 128.93

IMP, investigational medicinal product.

The CTs that ended with no recruitment accounted for 57.45% of the negative balance. Table 2 shows the relation between the costs assigned and the amount billed by different departments according to whether the trial enrolled any patients.

Table 2.

Costs of the pharmacy department’s participation and amount received, in trials with inclusion of patients and in trials closed without patients included, broken down by clinical department involved in the trial

Clinical department	n	Trials with patients included (n=89)		Trials closed without included patients (n=45)		All trials (n=134)
		Calculated cost for pharmacy department	Amount received	Calculated cost for pharmacy department	Amount received	Calculated cost for pharmacy department	Amount received
Anaesthesiology	2	€895.5	€887.4	€492.3	€0.0	€1387.7	€887.4
Cardiology	4	€6093.6	€3604.7	€ 0.0	€0.0	€6093.6	€3604.7
General and digestive surgery	1	€1542.2	€0.0	€0.0	€0.0	€1542.2	€0.0
Vascular surgery	1	€4042.4	€1864.4	€0.0	€0.0	€4042.4	€1864.4
Orthopaedic surgery	3	€3510.3	€3846.0	€0.0	€0.0	€3510.3	€3846.0
Critical care	2	€4359.0	€1641.4	€0.0	€0.0	€4359.0	€1641.4
Dermatology	3	€4383.5	€2181.1	€0.0	€0.0	€4383.5	€2181.1
Digestive diseases	8	€5142.2	€1658.2	€3996.3	€0.0	€9138.5	€1658.2
Endocrinology and nutrition	13	€17 560.6	€20 902.1	€2508.9	€761.3	€20 069.5	€21 663.3
Haematology	6	€10 013.2	€6663.3	€2842.5	€17.0	€12 855.7	€6680.3
Internal medicine	2	€1061.6	€53.4	€538.8	€0.0	€1600.4	€53.4
Nephrology	2	€10 541.3	€10 454.8	€0.0	€0.0	€10 541.3	€10 454.8
Pneumology	15	€20 554.6	€26 791.6	€3546.2	€85.5	€24 101.1	€26 877.0
Oncology	30	€33 439.7	€34 353.7	€12 555.2	€231.2	€45 994.9	€34 584.9
Otorhinolaryngology	1	€0.0	€0.0	€1970.4	€0.0	€1970.4	€0.0
Paediatric medicine	10	€15 756.1	€5844.7	€983.1	€0.0	€16 739.2	€5844.7
Rheumatology	25	€28 905.2	€25 253.4	€3795.3	€0.0	€32 700.5	€25 253.4
Mental health	5	€3546.1	€1619.5	€1348.0	€45.7	€4894.1	€1665.2
Urology	1	€1448.3	€368.2	€0.0	€0.0	€1448.3	€368.2
Total	134	€172 795.3	€147 987.8	€34 577.3	€1140.7	€207 373.0	€149 128.9

Table 3 shows the relation between the mean amounts to be paid per patient extracted from the financial records of contracts with sponsors, the actual amount billed to the sponsors per patient, and the mean cost per patient for the pharmacy department. The mean amount received per patient was lower than the one expected according to the contract agreement. Table 4 shows the total amount received and the total cost for the pharmacy department for the 134 trials as well as the difference between the two amounts according to the fee applied by the pharmacy. While the balance was positive for those trials with a pharmacy fee of 10% and 15%, for trials with a 5% fee (the majority) the balance was negative.

Table 3.

Amount per patient according to the contract agreements and received from the sponsors, and mean cost per patient for the pharmacy department

Type of sponsor	Mean amount per patient to be received according to the contract			Mean amount received from sponsors			Mean cost per patient for the pharmacy department
	5%	10%	15%	5%	10%	15%	5%	10%	15%
All sponsors	€313.33	€715.53	€1081.87	€268.11	€592.46	€741.68	€565.02	€282.40	€851.52
Commercial sponsors	€323.39	€808.25	€1081.87	€275.63	€592.46	€741.68	€567.99	€282.40	€851.52
Non-commercial sponsors	€97.15	€58.70	–	€42.61	–	–	€475.82	–	–

Table 4.

Difference between the total amount received and the costs incurred by the pharmacy department

Type of sponsor	n	Total amount received			Total cost for the pharmacy department			Difference between the pharmacy department’s costs and the amount received
		5%	10%	15%	5%	10%	15%	5%	10%	15%
All sponsors	134	€66 700.4	€15 080.0	€65 476.6	€115 190.0	€7806.3	€46 160.9	€48 489.6	€7273.7	€19 315.7
Commercial sponsors	126	€66 291.3	€15 080.0	€65 746.6	€111 170.7	€7806.3	€46 160.9	€44 879.4	€7273.7	€19 585.7
Non-commercial sponsors	8	€409.1	–	–	€4019.3	–	–	€3610.2	–	–

The oncology department was the department with the highest proportion of CTs for which the pharmacy department received no compensation; 34/90 (38%) CTs ended up with no recruitment and 18 (20%) were sponsored by cooperative groups that provided no financial support for the study. Thus, we estimated the mean cost per oncology CT without payments to be €1100, and this amount is proposed as down payment for all trials. Conversely, the same calculation was done for the non-oncology CTs giving a result of €875.

Discussion

Economic impact of the CTs in which patients were included

Our results show that the current system based on percentages fails to cover the costs related to the pharmacy department’s participation in CTs. This is most evident in the trials where the department receives 5% of the amount billed to the sponsor. By contrast, the department receives nearly twice the amount of the costs incurred in the trials with a 10% fee and nearly 30% over when the fee is 15%. However, in more than half of all the trials the compensation was set at 5%. The only exceptions were the departments of oncology and haematology, which participate in more trials in which it is necessary to prepare and administer the drugs in a hospital outpatient facility, and thus the participation fee is set at 15%. Due to the high proportion of trials with a 5% fee, the gains from participation in trials that pay a higher percentage were insufficient to cover the losses, making the overall result of participating in CTs negative.

The oncology department participated in more CTs than any other department and also had the highest proportion of trials with a 15% fee. However, the gains from these trials are insufficient to cover the pharmacy department’s overall expenses in participating in CTs, due to the large number of trials closed with no recruitment or with non-commercial sponsor.

The only departments whose trials were nearly all classified in the 5% compensation group but paid the pharmacy department enough to cover the costs of participation were the departments of endocrinology and pneumology. Closer analysis revealed that these departments participated in one (endocrinology) or two (pneumology) trials for which the sponsors paid exceptionally high compensation for each patient.

We were unable to evaluate the differences between the payments and costs of the CTs with a non-commercial sponsor, where no financial compensation was agreed on because only a very small number were included.

Economic impact of the CTs in which no patients were included

Some studies have suggested that about half of all CTs fail to achieve their target recruitment both in timelines and number of patients.^9–12 Failure to achieve the prespecified sample size of the trial increases the risk of a type II error in the results (failing to detect significant differences that exist between groups).¹³ Delays in recruiting participants can require adjustments to the timeline of the study, which can potentially increase costs, delay interventions that might benefit the study population, or allow harmful or inefficacious interventions to be employed for longer than ethically appropriate. In the worst of cases, the failure to recruit the target sample size can lead to early termination of the study before the research question has been addressed.¹⁴

At our hospital, 34% of the CTs ended without recruitment. These trials have a huge impact on the budget of our pharmacy department’s CTA because the costs that are not covered (€34 577.34) account for 57.4% of our losses.

About 69% of the CTs that ended without recruitment required the pharmacy department to receive, store, maintain and destroy samples of mediations as well as to carry out visits with patients. With the exceptions of the endocrinology and pneumology departments, none of the departments was able to pay the pharmacy department more than was spent on carrying out tasks related to the trials. For some departments (anaesthesiology, oncology, digestive diseases, and mental health) the costs of these trials represent half of the costs of our collaborations in trials with these departments. It is of utmost importance to analyse which factors contribute to the low rate of recruitment at our centre and to implement strategies that may help to tackle this problem in future trials, such as a comprehensive assessment of the viability of the trial in our hospital (availability of patients, facilities and competing trials) and close management of the whole process.

Evaluation of the cost of the pharmacy department’s collaboration

Due to the increase in the activities related to CTs, the pharmacy department needs to have personnel and facilities exclusively dedicated to such activities which otherwise would not be necessary. At our pharmacy, the activity related to CTs and the activity related to clinical assistance are completely differentiated. The CTA’s infrastructure (overhead costs) accounted for 57.5% (€119 241.45) of the costs of the pharmacy department’s participation in CTs. Calculation of the overhead costs was a challenge; we only included CTs initiated between 2014 and 2018 and finalised before 31 December 2019. This represents about one half of all trials active in our centre during this period. Thus we prorated the cost of infrastructures according to the period that the study was active and taking into account all CTs active during the period. The CTA’s infrastructure represents a large proportion of the expenses derived from the department’s participation in trials. Thus, in future analysis we will focus on more accurate methods for estimating these costs as they may have a huge impact on the balance.

Evaluation of the cost of the activity generated by the CTA

To assign a cost to each CT, we used a full costing system based on the activity, which considered all the expenditures necessary to allow the department to provide the service. We created a cost allocation formula that took into account both direct and overhead costs. Unlike businesses that decide to include a profit margin when setting the prices for goods and services, our formula was applied with the sole purpose of ensuring that the costs generated in participating in trials would be covered.

It would be very interesting to compare our findings with those of other studies. However, to our knowledge, no recent studies addressing these issues have been published.

Initial payment for opening CTs and service portfolio

Given our results and considering the financial impact of CTs that fail to recruit any patients, we are considering not only charging fees for the services we provide when collaborating in CTs, but also establishing a down payment for opening CTs. This would be a two-tiered system, with one fee for trials managed by the oncology department (€1100) and another for trials managed by other departments (€875). If the trial ends up recruiting patients, we will bill our work based on the actual costs, and the down payment will be subtracted from the total amount due. However, if the trial fails to include any patients from our centre, the initial payment will not be reimbursed; rather it will serve to cover the costs the department incurred in collaborating in the trial. The down payment will be waived for trials with a non-commercial sponsor. In this case, when the trial ends, the sponsor will be billed according to the costs we incur if patients have been included (only in the case that a financial contribution has been considered between the centre and the sponsor); however, if no patients have been included from our centre, the sponsor will not be billed.

This study has enabled us to establish a portfolio of fees for the services our department provides for CTs, based on the direct and overhead costs of our collaboration.

The distribution among the different departments/structures within the institution is a rule established by the research foundation and agreed on by all parties. This work is intended to set the basis for a new system of distribution of the amounts paid by the sponsor, but could also lead to a system where the pharmacy department invoices separately to the sponsor for the tasks performed. However, we think that a unique agreement between the institution and the sponsor is the best scenario, as multiple contracts add complexity to the process. The institution should establish agreements for how the payments should be distributed and each department involved should develop a budget for each CT according to the actual costs of the tasks.

The main limitation of this work is that this is an analysis performed at our centre, thus extrapolation to other institutions or regions may not be straightforward. Also, the calculation of costs for the different tasks was derived from the CT performed during a period and this may change if the complexity of the CT changes. Thus, these costs should be periodically reviewed and updated.

The new system in which the pharmacy department will charge fees for services and an initial fee for opening CTs has yet to be implemented at our centre. For this reason, we cannot analyse the extent to which sponsors will accept this approach, which we consider fairer for our department. The new system should not necessary represent an increase in the expenses for the sponsor but a change in the distribution of the fees across the different departments involved in the CT at the study site and this will contribute to the transparency of structural costs.

This work may be of use as a starting point for those who would like to assess the adequacy of their current system and to develop a more accurate one. We look forward to the publication of similar studies so we can compare our results and conclusions with those of authors at other centres.

Conclusions

The current system in which the pharmacy department’s remuneration for collaborating in CTs is based on percentages is inadequate to cover the costs generated by the CTA. By contrast, payment based on the direct and overhead costs of our collaboration would ensure that our expenses are covered.

This study has enabled us to establish fees for the items that make up our portfolio of services so that we can charge the sponsors of CTs at the end of the trial. Conversely, at our centre, CTs that fail to recruit patients accounted for more than half of the unpaid costs of the CTA, so establishing an initial payment based on the costs generated by these studies will guarantee that our costs are covered once the trial finishes.

Finally, we have designed a billing programme that will enable us to bill sponsors quickly and easily at the end of the CT.

What this paper adds.

What is already known on this subject

• Pharmacy departments’ participation in clinical trials involves financial costs and benefits, but the balance of costs and benefits remains to be determined.

What this study adds

• The pharmacy department at our hospital loses considerable amounts of money by participating in clinical trials, mainly due to the lack of compensation for contributions to trials that do not recruit patients and those done for cooperative groups.

• Charging fees based on costs and setup fees for opening trials would be fairer than the current system.

Data availability statement

No data are available. Most of the data generated in this study are confidential as they are related to the financial accountability of the hospital. Only aggregated data are provided.

Ethics statements

Patient consent for publication

Not required.

Ethics approval

The research ethics committee at our centre (Comité Ético de Investigación Clínica de la Corporació Sanitaria Parc Taulí) approved this study.