International Biopharmaceutical
Association Publication
Conducting Clinical Trials in South Africa and China: A Comparison between
Advantages, Disadvantage and Difficulties
Abstract:
As South Africa
is a country well known for the quality of its clinical research, its
affordability and the fact that it has a big pool of treatment-naďve patients,
the decline in the number of clinical trials conducted in South Africa is interesting. Looking
at numbers as obtained from www.clinicaltrials.gov
website, there are twice as many clinical trials that are open and recruiting
in China as in South Africa. There is a move from all the major players in the
pharmaceutical and clinical trial industries towards the East – China in
particular. The huge pool of treatment – naďve subjects and the relative low
cost of conducting clinical trials in China makes it a very attractive
proposition.
As clinical trials is by nature a very costly and lengthy
process, it leads to the question of why the shift away from a country that has
a proven track record towards a country with limited experience in clinical
trials.
It is estimated that $32.1 billion dollars will be spend on
conducting clinical trials by 2011. The amount spent in 2005 was $24 billion
and $25.6 billion in 2006.
Pharmaceutical companies are constantly looking for ways to
reduce this cost. One of the main contributing factors to the high cost of
clinical trials is the delays in recruiting subjects onto a clinical trial and
then retaining them. It is stated as a fact that over three-quarters of all
clinical trials currently fail to meet their recruitment deadlines. Thus, the
pharmaceutical companies are looking for a huge pool of study subjects in order
to meet recruitment deadlines at a cost that will not break the bank.
In comparing the advantages, disadvantages and difficulties
facing the pharmaceutical companies conducting clinical trials in South Africa and China, this article is aiming at
finding the possible reasons behind the shift towards the East.
What are the advantages, disadvantages and difficulties
facing pharmaceutical companies conducting clinical trials in these two
countries?
Advantages:
The advantages to conducting clinical trials in South Africa
start with the existing medical infrastructure. Although South Africa is in
many ways considered to be a third world country, it boasts a medical
infrastructure – in both personnel and facilities - that equals that of
European countries and the USA
in quality. The standard of care in both public and private healthcare also
equals the care in Europe and the USA.
Training of the South African medical personnel is also
internationally recognized. Hand in hand with the training and quality of the
medical infrastructure goes experience. Until 2005, more that 400 clinical
trials per year have been conducted in South Africa. Serving the
pharmaceutical companies in their clinical trials are very experienced CRO’S,
laboratories and investigators. This experience also includes Good Clinical
Practice and International Conference of Helsinki guidelines. Data from studies
conducted in South Africa
have been widely accepted by the U.S. Food and Drug Administration (FDA) and
the European Agency for the Evaluation of Medical Products (EMEA).
Noted also is the growing “medical tourism” phenomenon in South Africa
– a testament to the quality of the South African health care system. It is
estimated that about 100 000 tourists traveled to South Africa from all over the
world in 2003 for medical procedures.
This brings us then to the second advantage: affordability.
As a result of the country’s lower labor costs and a favorable exchange rate,
South African clinical trials typically provide a substantial cost savings
compared with those conducted in North America and Europe.
This is especially important for the generic manufacturers due to the high
level of competition in their segment of the pharmaceutical industry.
The third advantage is access to subjects. More than 50% of South Africa’s
population is concentrated in urban areas, providing sponsors with ready access
to large numbers of potential subjects. A significant portion of this
population is treatment – naďve – a major factor at a time when shortages of
available and qualified subjects constitute a major source of delays in the
clinical development process. The growing HIV/AIDS epidemic in South Africa
also offers the opportunity for clinical and epidemiological HIV related
clinical trials.
The fourth advantage is South Africa’s location in the
Southern hemisphere. With the seasons in South Africa opposite to that in
the Northern hemisphere, subjects for global studies of seasonal conditions are
available year round, having the potential to significantly reduce enrollment
time.
What has attracted so many companies to China is its
huge market and high economic growth. As mentioned before, China has the
largest national population in the world – estimated at 1.33 billion. This fact
has opened a market for clinical trials on populations with diseases of both
the developed and developing world, with the attraction of rapid subject
recruitment.
Secondly, China
represents one of the fastest growing pharmaceutical markets in the world and
is the most lucrative market in Asia. In 2005,
China
was the 7th largest pharmaceutical market. With its huge population expected to
substantially increase its consumption of Western pharmaceutical products, it
is expected to become the largest pharmaceutical market in the world.
As a third advantage, China has a motivated workforce.
Most of the region’s leading specialists are English-speaking and have received
their postgraduate medical training in the United
States or United
Kingdom. The levels of experience in the
labor market are variable, but numerous training initiatives have been arranged
by the state and private organizations. This is an attempt to teach candidates
with a biomedical background the principles of GCP- compliant clinical
research.
The fourth advantage for conducting clinical trials in China is the
opportunity for cost savings. Investigator and site fees are approximately
one-half of those in the US.
Further costs to the sponsor for providing trial-related medication,
investigations and hospitalization could be as low as 30% of those in America. Labor
costs are also less.
Disadvantages:
Looking at the disadvantages and difficulties of conducting
clinical trials in both South Africa
and China,
it is obvious that they share one major obstacle: time lines for protocol
approval.
In South
Africa, it takes an average of 12 – 14 weeks
from the time an application is submitted to the Medicine’s Control Council
(MCC) until a decision is rendered. From the submission deadline, there is also
a one-week validation process when the MCC can request information omitted from
the original submission. Four to five weeks after the original submission
deadline, the clinical trials committee (CTC) meets to discuss the application
and may provide feedback to the applicant. Another five weeks after this, the
MMC meets to discuss the application and responses. The results of the
assessment are delivered to the applicant after the MMC meeting. In addition to
MCC approval, all clinical trials must be approved by an accredited ethics
committee. The average approval time for ethic committees are two weeks.
Regulatory approval all over Asia is longer than in North
America, but they are even more prolonged and unsure in China. Regulatory approval in China for a
clinical trial initiation may take up to nine months as the approvals dossier
navigates its path through six regulatory approval bodies. In October 2007, it
was confirmed that China
will now shorten its IND
approval time by more than half, reducing the target for approval to four
months (16 weeks).
Another difficulty facing pharmaceutical companies with
their head quarters outside of China
is the very strict and lengthy import regulations. There is a mesh of permits
to negotiate through. In some cases reagents have reached their expiry date by
the time all the needed import permits have been obtained and approved.
Considering the cost of reagents, this can make a huge impact on the overall
cost of conducting clinical trials in China.
Another cost to offset the low cost of labor in China,
is the mandatory investments in training and support systems to ensure data
quality.
Many patients in South Africa who participate in
HIV/AIDS treatment trials have no alternative access to drug therapy. Where a
patient has a therapeutic response to a study drug, that patient should be
offered ongoing treatment. In designing studies, consideration should be given
to the costs of long term provision of study drugs and of clinical monitoring,
including the costs of medical staff. The duration of drug therapy in a study
should be clearly stated in the patient information section of the informed
consent document.
Difficulties:
Each of these countries also offers their unique challenges.
Import regulations in China, the refusal of the Chinese government to allow DNA
from any Chinese national to leave China along with the challenges that go hand
in hand with a country new to GCP and GMP, makes for very interesting - and sometimes very frustrating – times.
In South
Africa, the guidelines for conducting
clinical trials states that “Where a patient has a therapeutic response to a
study drug, that patient should be offered ongoing treatment. In designing
studies, consideration should be given to the costs of long term provision of
study drugs and of clinical monitoring, including the costs of medical staff.
The duration of drug therapy in a study should be clearly stated in the patient
information section of the informed consent document.”
Conclusion:
In conclusion it can be said that conducting clinical trials
in South Africa and China have a lot in common.
Both countries claim to have a huge potential for patient
recruitment (China has the total number advantage), both show lower overall
cost for conducting clinical trials and both countries provide unique
opportunities that can be of use to pharmaceutical companies. In China,
the use of Western medicine in combination with traditional Chinese medicine
provides a new challenge – one that can be of great benefit to the
pharmaceutical industry, if approached correctly.
With regards to unique opportunities in South Africa - and Africa
as a continent – it is indicated that “…between 1975 – 2004, only 20 out of
1556 new drugs that appeared on the market treated parasitic and infectious
diseases that kill 15 million people every year. Barely 10% of medicinal
research is currently dedicated to illness responsible for 90% of worldwide
death – that is where the needs are greatest. It is thus critical that research
be conducted in Africa and the developing
countries to test new drugs for malaria, sleeping sickness and chagas disease
that sick people in poor countries need and these tests should always be
conducted in an ethical way.”(Comment made by Dr Jean-Harve Bradol, President
of the French section of Medecins sans frontiere).
As far as disadvantages and difficulties go, the two
countries also share one major obstacle: approval times. China has promised a major
improvement in clinical trial approval, but it will still take up to four
months to initiation. In South
Africa the average time for approval is 12 –
14 weeks.
Thus still leaving the question: Why then - faced by very
similar advantages, disadvantages and difficulties in both South Africa and China
– is there this shift towards China?
References:
1. The US-based register www.clinicaltrials.gov
2. Richard Shannon, Head of Business Development (Europe), Clinical Trial Services (CTS), Supplying the
Needs of Emerging Markets – Understanding Clinical Trial Logistics, www.cts-almac.com.
3. Next Generation Pharmaceutical Article, Clinical Research
in South Africa,
article 273200, issue 246, www.ngpharma.com.
4. Herman Scholtz, Sybrand Pretorius, Applied Clinical
Trials, Article: Discovering South Africa: A high-quality medical infrastructure
and low costs make South Africa an untapped
opportunity – an attractive alternative for conducting clinical trials, www.appliedcliniclatrialsonline.com
5. Dr. Emmanuel Sena K Damalie, Biopharmaceutical Industry:
The Untapped Potential in Africa, The
International Biopharmaceutical Association Magazine, May 2008,
www.ibpassociation.org.
6. ChinaBio Today, Biotech Week in Review: The Allure of
Conducting Clinical Trials in China,
08 October 2007, htpp://seekingalpha.com, article 49138.
7. Robert Fee, Managing Editor, The Cost of Clinical Trial,
Drug Discovery & Development – Mar 01, 2007, www.dddmag.com
8. Heather E. Fraser, Dr. Sally Drayton, Andy e. Wang, Delay
no More: Improve patient recruitment and Reduce Time to Market in the
Pharmaceutical Industry, www.935.ibm.com
9. A Bright Outlook
for Clinical Trials in China,
Clinical Researcher, Volume 2, Number 12, December 2002
10. Nermeen Varawalla, Conducting Clinical Trials in Asia, Applied Clinical Trials,
01 Jun 2006, www.appliedclinicaltrialsonline.com
11. The Guidelines for Good Practice in the Conduct of
Clinical Trials in Human Participants in South Africa, www.doh.gov.za