Winter 2007
21st Century Solutions to Clinical Trials in Africa

The World is changing and the Pharmaceutical/Biotechnology landscape is no different. The US and European markets, are being out-paced and out-projected by new and emerging markets. Asia is leading the way but the African countries are rapidly positioning themselves to take up their place in this new World order.

Agencies such as the European and Developing Countries Clinical Trials Partnership (EDCTP), Malaria Clinical Trials Alliance (MCTA), Malaria Vaccine Initiative (MVI) and the Medicines for Malaria Venture (MMV) are all established to manage the funding and execution of clinical research in developing countries, particularly in Africa, and especially for HIV/AIDS, Tuberculosis and Malaria.

What is so special about Africa?

It is the second-largest and second most-populous continent, after Asia.
It covers 11,668,545 sq miles (20.4% of the Earth's total land area.
It houses 933,448,292 people (estimated 2007)
It accounts for 14.2 % of the world's human population.
The number of Africans 60 years and over will increase from 22.9 million in 1980 to 101.9 million in 2025; by which time over 64% of Africa's elderly will live in areas defined as rural.

Performing Clinical Trials in Africa

There is a well documented demand for performing clinical trials in Africa and yet performing clinical trials in Africa is far from easy. Aside from the political and geographical limitations, there remains a lack of adequately resourced research centres, and the infra-structure of most countries in Africa is far from ideally suited to performing clinical trials.

However, it is perhaps the technology infrastructure that presents one of the most pressing challenges. This is the most significant area that a UK-based study team can do little to alter, or even fully appreciate. There is a growing determination amongst the industry to utilise electronic data capture (eDC) to collect and manage the clinical trial data generated from every study. Traditional web based eDC systems require two critical ingredients in order to deliver; Power (Electricity) and Internet Connectivity.

The former is somewhat readily overcome through imaginative and not-so imaginative solutions. The latter is far harder to provide, and it is this area that provides us with a massive and costly challenge when considering the use of eDC in African trials. For, by their very nature, web based systems are dependent on the wide scale availability of adequate internet connectivity.
Availability
In Europe and North America, use of the Internet is taken much for granted. Most of us use it every day, both for professional and personal reasons and as such the Internet has been fully integrated into our everyday way of life. In Europe, 41.7% of the population can readily access the internet; and that number increases to 70.2% in North America (source: www.internetworldstats.com).

For the purposes of running clinical trials in Europe and North America, it is similarly assumed therefore that the appropriate Internet connectivity will be available to support eDC.

% Penetration by World Region
Number of Internet Users (in Millions)

However, compare this number to those observed and recorded for Africa. Only 4.7% of the population have any level of access to the internet. Put another way, only 3.5% of the World's Internet users are located in Africa. Can we therefore safely assume that for the purposes of running clinical trials in Africa, the availability of Internet connectivity will support the usage of eDC?

% Usage of the World
Adequate

"Adequate" is described in the Oxford dictionary as "adjective satisfactory or acceptable".

In terms of Internet access, one way of considering "adequate" is to consider screen re-refresh times. Consider "Google" for one second, a company that has always paid attention to how fast its search results come up. Google appreciates that using an application – even one as simple as search – is not the same as browsing the Web. Users are prepared to wait a few seconds for a page to load if they're planning to read it, but if they're in the middle of a process they have a different mindset: they're impatient for the page to load so that they can click the next button and get closer to completing the process.

Now imagine that you are an Investigator, waiting 10, 20, 30, maybe 60 seconds for a page to re-fresh. Does this meet your definition of "adequate"?

We all know that any system can perform under the perfect conditions, but how often to we actually observe these "perfect conditions"? What happens when users are in a situation where their connection no longer supports the work they are trying to perform? Simple answer, they stop performing the task.
Another way to consider "adequate" is using a "ping" test to measure round-trip travel time along major paths on the Internet. The results of the ping test can then be presented as either;
Current Index: Graphically display whether the response was bad or good on a scale of 0 (slow) to 100 (fast)
Response Time: how long does it take for a chunk of data to travel from point A to point B and back (round trip)?
Packet Loss: measures the reliability of a connection. In a perfect world 0% packet loss is what we all want – every packet we send out makes it to where it's supposed to go. The higher the packet loss percentage, the slower the connection will work because in most instances it has to re-send the same piece of information several times before it is successful.
Current Index by World Region
Response Time (ms) by World region
Packet Loss (%) by World Region
So What Does This All Mean?
Put simply, the divide between Internet Performance in Africa and North America or Europe is huge. Basing your expectations for eDC performance in Africa on your observations in London or New York, is unrealistic and will almost certainly lead you to disaster.
The Future of Internet Activity in Africa
The market for internet access and services in Africa is growing fast, but the overall number of internet users remains limited, and a number of very significant hurdles still restrict further growth. The main factors dampening uptake are widespread poverty that makes internet services unaffordable, low literacy levels that limit demand, poor telecoms infrastructure and high operating costs that continue to keep service prices high. There is simply not enough existing infrastructure in Africa. In much of sub-Saharan Africa there are few fixed landlines and sometimes none; e.g. Uganda has fewer than five fixed lines per 100 people and (as with most African countries) does not have enough resources to build huge fixed-line infrastructure, much of which was state-funded in the west.
The Solution? Mobile Phone Connectivity in Africa
More Africans have begun using phones since 2000 than in the whole of the previous century. There are now more people using mobile phones across the continent than traditional, fixed lines.

Over the next 5 years, mobile phone companies will invest $50bn (£25bn) in sub-Saharan Africa, with the established aim of providing more than 90% of the population with mobile coverage.

Imagine an eDC system that operates over a GSM network. Imagine a system that does not need a land line, or a broadband connection. Would it be subject to the same failings as traditional web-based eDC ? An eDC system that could harness this power would surely be far better placed to meet the growing needs of these clinical trials.

The Advent of GSM (Global System for Mobiletelephones)
GSM is one of the few mobile phone standards with a self-explanatory name that is actually more or less accurate. It's the closest thing there is to an "international" standard. GSM systems are used in nearly 200 countries (with 600 million subscribers) worldwide, from Europe (where the standard originated) throughout Africa, Asia and Australasia; and indeed more recently North America. Most cell phone manufacturers offer dual-band, or tri-band, or even quad-band phones, so we can work practically anywhere GSM systems are found.
Conclusions
In the so-called developed World, we are all guilty of taking access to the internet for granted. The internet is now part of our every day life, and, when we plan clinical trials, it is all too easy to assume that eDC will provide a trouble free solution. In reality, even within Western Europe and North America, we continue to meet daily challenges concerning the adequate provisioning on Internet connectivity.
However, in the so-called Developing World, the playing field is very different. The infrastructure that dictated so many decisions in the development cycle of the Internet, simply does not exist. As such, we must look to the next generation of solutions to guide us. The year 2008 will see an explosion of mobile solutions, and it is these solutions that the eDC market must seize if we are to successfully run trials in Africa; we have only shown Africa by way of example but it is not difficult to imagine similar issues in other developing regions. The challenge for clinical trials will be determining whether your eDC solution can utilise these, or whether the pipe dream will just have to continue for another year.
Richard Young
Cmed