CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
250
AFRICA
visit to payment of the receipt, including the time from the
patient’s visit to invoice generation, as well as invoice generation
to site payment. A total of 4 771 patient visits were included in the
analysis, 2 433 (51%) from CROs and 2 338 (49%) from pharma-
ceutical companies. This resulted in 67 invoices being generated;
34 for CROs and 33 for pharmaceutical companies. The results
of this analysis are presented in Fig. 1. On average, the time from
the patient’s visit to site payment was 134.3 days (4.5 months) for
CROs and 122.7 days (4.0months) for pharmaceutical companies.
The main findings of this retrospective analysis are that
payments per patient per visit over the past six years at this site
have not kept up with local inflation figures and that risk-factor
studies’ payments increased by 13% yet the CVS endpoint stud-
ies’ payments decreased by 7% over the same period. The aver-
age time from patient visit to payment receipt was 134 days (4.5
months) on average for CROs and 122 days (4.0 months) for
pharmaceutical companies.
Billing for ‘hidden costs’
Typically, sites in South Africa only receive the study budget
once they have agreed to conduct the study and there is
seldom any mention in the contract of annual inflation adjust-
ments, despite the fact that site expenses such as staff-related
costs, consumables, equipment and infrastructure-related costs
increase annually by at least 8% locally. An unspoken rule of
thumb in the clinical trial industry locally has been to charge
Medicines Association of South Africa (MASA) rates plus 10%.
There is, however, no standardised or formalised approach to
billing for procedures or components specific to clinical trials.
Kaiser Permanente is a large American research institute,
which recently implemented a system of analysing and billing
for the various components of clinical trials. These components
include ‘direct components’ such as the costs of specific clinical
procedures and research costs versus ‘indirect costs’, such as
those incurred by supporting a site’s infrastructure, especially
regulatory and administrative costs, which are by their nature
‘hidden costs’.
3
The equation states that the per-patient ‘direct
costs’ plus ‘indirect costs’ equal the total per-patient rate for
the study. Their approach translates research and administrative
activities into relevant costing codes by using the same logic as
that applied to clinical procedures when claiming from medical
aids, for example.
3
Examples of some of these costs inherent
to clinical trials include site staff time at investigator meetings,
time spent with study monitors, advertising costs, archiving fees
and time required to report serious adverse events (SAEs) and
endpoints. Other ‘hidden costs’ for which sites are not remuner-
ated include audit preparation costs, unscheduled visits, screen
failures and pre-screen costs.
2
Increasing clinical trial complexity
Clinical trial budgets have also not taken the median increase in
procedures per clinical trial into account. Getz reported a 49%
increase in procedures from 2000–2003 to 2004–2007, while
the total effort required to complete these procedures grew by
54%.
1,2
This increase in site effort and time is not reflected in the
per-patient payment schedule, with a reported 27% decline in per
procedure payment over their analysis period. Their study also
found a wide variability in the complexity and execution burden
between therapeutic areas and clinical study phases.
The present study compared risk-factor and CVS endpoint
studies and found that average payment for CVS endpoint stud-
ies has decreased by 7% over the last six years at this site. This is
despite the fact that these endpoint studies require an incredible
amount of manpower to complete the required reporting needed
to meet their primary statistical endpoints. The American Food
and Drug Administration (FDA) drafted a recommendation:
‘Endpoints and standardised data collection for cardiovascular
endpoint trials’ in July 2009. These recommendations, if and
when adopted, will mean that site staff will be spending even more
time collating and submitting data for these CVS endpoint trials.
Delayed payment
Our study also found that the time from patient visit to site
payment took on average 128.5 days (mean time in days from
both the CROs and pharmaceutical companies). The study by
Getz
2
reported that it takes pharmaceutical companies on aver-
age 140 business days to pay an investigator for work already
performed. The present study had similar findings, with CROs
taking on average 134 days to pay and pharmaceutical companies
taking 122 days. This delay in payment is often despite agreed
payment deadlines in the CTA. Such payment delays have hugely
adverse effects on a site’s cash flow since monthly expenses and
creditors still need to be paid timeously.
While there may be many contributing factors to explain this
excessive payment delay, one reason often cited by pharmaceuti-
cal companies and CROs alike is that they are unable to pay for
work that has not been monitored. Invariably, in rapidly recruit-
ing studies and studies that generate a large volume of data, the
monitoring visits fall behind and therefore the time to payment
lengthens. A possible solution would be to ensure that allow-
ances be made in study budgets for more frequent monitoring
visits, especially during the recruitment phase of the study. This
would ensure that monitoring remains on track with data collec-
tion, invoices can be generated faster, and payments processed
within a more reasonable time frame.
Conclusion
Investigators and the pharmaceutical industry alike need to
acknowledge that clinical research has to be run like a business.
2
This includes making allowances for annual inflation in study
budgets, incorporating all trial-related procedures into the budget
and taking pro-active measures to ensure that site payment is
made promptly.
LJ BURGESS, MB BCh, MMed (Chem Path), PhD, Dip Int
Res Ethics,
NU SULZER, BSc (Med) (Hons), MSc (Med)
TREAD Research/Cardiology Unit, Department of Internal
Medicine, Tygerberg Hospital and University of Stellenbosch,
Parow, South Africa
References
1. Getz K. Rising clinical trial complexity continues to vex drug developers.
ACRP Wire
13 May 2010
). Accessed 13 May 2010.
2. Getz K. Have we pushed our PI’s too far?
Appl Clin Trials
Online
1
September 2005
). Accessed 09
June 2010.
3. StollerS.FinancingclinicaltrialsresearchasKaiserPermanente.
Permanente
J
2001;
5
(2).
). Accessed June 2010.
