Magazine Article | August 1, 2012

Africa – The Next Frontier For Novartis Clinical Development

Source: Life Science Leader

By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL

Just as people distinguish between “old” and “new” Europe, the healthcare industry is beginning to distinguish between “old” and “new” emerging markets. The BRICs (Brazil, Russia, India, and China) are the “old” and have been increasingly suffering from the law of diminishing returns. A 2010 article in The Economist classified the “new” emerging markets into two categories — “overlooked” and “frontier.” Overlooked markets can rival the BRICs in terms of prosperity, while frontier markets are poorer and riskier than their overlooked counterparts. The biggest concentration of these markets just happens to be in Africa. Though many of these markets are known for being unpredictable, prone to whims of nature, wiles of dictators, and wills of Somalia’s pirates, they also represent huge growth opportunities.

With a population second only to Asia’s and forecasted to grow faster than those of Europe, Latin America, and North America, it is anticipated that by 2050 Africa will have a population of around 2 billion. No wonder Novartis (NYSE: NVS), with nearly 120,000 employees worldwide and sales revenues of $58.6 billion (up 16% vs. last year), sees Africa as the next frontier in emerging markets. Debra Barker, M.D., chief science officer for Novartis group emerging markets (GEM), has spent a lot of her career in the emerging markets. Responsible for clinical development and regulatory affairs across all Novartis divisions for a number of small, dynamic emerging markets, Barker shares her insights as to why Novartis sees Africa as one of the next frontiers for clinical development, the company’s approach to market entry for clinical trials, and associated lessons learned.

Clinical Trials Expansion In Emerging Markets
Though Novartis has been in Africa for a long time, the strategy for entering the frontier markets in Sub-Saharan Africa was advanced further with the foundation of the Region Group Emerging Markets (GEM), which includes some small, dynamic emerging markets in various continents, amongst which are a few countries in sub-Saharan Africa. As a complement to the business strategy, the company is also planning to increase its investment in clinical trials in the region to ensure that drugs developed there meet the unmet medical needs of the local communities.

Originally started as a pilot in nine countries in 2008 to help fulfill unmet medical needs in smaller emerging economies, GEM has helped Novartis accelerate year-over-year growth in selected countries across various continents. The idea behind GEM was to create a team which could quickly align efforts across the divisions of Novartis to meet the customer and patient needs and become the “local partner of choice” in some smaller emerging countries. Prior to the Novartis GEM setup, if a hospital in Kenya wanted to procure a variety of products, it would have multiple points of contact, such as Novartis Pharmaceuticals for oncology medications, or Sandoz for generics. According to Barker, the creation of the GEM team allows Novartis to be able to gain a greater understanding of emerging market medical needs and provide an integrated solution across the six different divisions. “The different divisional organizational structures don’t exist in GEM,” she says. “We are able to represent all the Novartis products to the healthcare professionals.” This allows for a more personalized level of service to healthcare professionals within countries of limited resources. Barker describes having been to emerging market clinics where they see 300 patients in a morning. “If a doctor and his nurses are going to see 300 patients in a morning,” she explains, “you can see the challenge for that doctor to spend half an hour to explain an informed consent document to enroll just one of the patients in a clinical trial.” When entering a frontier or emerging market to perform clinical trials, Barker suggests determining how to help these overwhelmed clinicians. One way is by making things easier, i.e. having one point of contact for necessary resources. This is what Novartis tries to address through the GEM organizational structure, providing access to clinical resources across all Novartis divisions to improve health care in some of Africa’s frontier markets.

Clinical Trials Lessons Learned  
Novartis has historically conducted clinical trials in South Africa — the continent’s biggest economy, accounting for nearly a quarter of its GDP. That being said, South Africa has nearly 25% unemployment, while another 25% live on a little over a dollar a day. Nonetheless, the country’s economic strength is 10 times that of Kenya and twice that of Nigeria — two countries Barker notes where Novartis has recently begun conducting clinical trials. “But it’s not easy,” she admits. “You have to be willing to make an investment.” The investment to which Barker is speaking involves time, money, as well as infrastructure — both physical and social. “Some hospitals might not have a fridge for storing trial drugs or blood samples properly,” she explains. “Certain equipment which is often taken for granted in many countries, such as  fridges, freezers, and even fax machines, are needed to support clinical trial work.”

Other investments might include supporting a clinic through a grant so that a clinic seeing 300 patients in a morning can hire a nurse to help manage the patients who are study candidates. With a  lighter workload, a doctor may have more time to spend on enrolling patients in clinical trials. Companies can consider providing the hospital a grant to invest in a research fellow to assist and support a clinical trial or pay a site-management organization to assist in identifying and supporting patients. “Maybe a doctor needs a separate room, as they don’t have an office where they can do clinical research,” says Barker. “They don’t have fireproof cabinets, and patients are often two to a bed,” she states. “Ask yourself how you can appropriately support the doctor to do his job.” As for time, Barker advises companies to be on the ground with their own staff so as to best determine what training needs to be done. “You have to put in about 100 times more effort and time than you think you would,” she affirms. Barker explains that when beginning trials in frontier markets, clinicians would describe having screened hundreds of patients, and yet, none had given informed consent. One reason is that clinicians are overburdened in their work. Another is the need for better clinician training on the informed consent process. Finally, Novartis found the importance of understanding the social and cultural infrastructure as well. “If you look at an informed consent form given to an American patient, it might be four to five pages long — fairly standard,” she explains. “American patients are generally very well-informed, make decisions quite independently, and have a good standard of literacy.” This same approach doesn’t tend to work as well in Africa, where literacy standards may be lower and patients seek advice from tribal elders. Novartis developed an informed consent program, which utilized storyboards and  pictures, and involved the patient as well as the tribal elders. The company was sure to be careful that tribal elders were helping to inform patients, but not coerce them to enroll in the clinical trial. “You have to be really culturally sensitive to what’s happening,” Barker confides. By implementing some of the above, Barker and Novartis saw a dramatic increase in clinical trial participation thanks to a better understanding from the patient of what clinical trial participation really means. As an example, she cites one diabetes study where, using a standard approach, only 10 patients of a needed 100 were recruited in the first six months the study was open, because people were suspicious of being used as “human guinea pigs” and thus, very reluctant to participate in the study. “In the final three months of the recruitment period, we switched to a strategy based more on discussing the consent and trial with the local community. This was successful, and the study was completed on time — much to our relief.”

Many of the metrics used to measure clinical development success can apply to frontier markets as well, such as the number of patients enrolled in clinical trials and the number of approvals. However, Barker reminds those interested in entering frontier markets to be less concerned about key performance indicators and more concerned with building both relationships and capabilities. There are other lessons to be learned. For example, according to Barker, the Novartis approach in developed markets is changing to more closely resemble how the company conducts trials in emerging markets. That approach also includes larger but simpler studies being asked for by the FDA and European regulators and an increasing emphasis globally on quality of life and affordability. “Shortening drug development processes in frontier markets is a long-term investment,” she states. “It’s about building for the future.”

The Importance Of Collaborations In Clinical Trials Development

Africa consists of 54 countries — more than the EU, more than Asia, and more than North and South America combined. In such a vast and diverse continent, one of the first challenges is to determine which countries or even regions to focus on. “In Africa, like in any other region where we operate, we want to make a difference in terms of impact on healthcare,” states Debra Barker, M.D., chief science officer for Novartis group emerging markets (GEM). In order to do so, clinical development efforts have been increased by establishing a significant medical presence in Kenya and Nigeria. “Africa is not just one big mass,” she explains. “The countries have their own individual cultures as much as any country in Europe.” Barker analogizes that trying to run operations in Kenya from an office based in Nigeria is similar to trying to run a China operation from an office in Japan.

She admits that for now, the company does not intend to have an office and run clinical trials in every African country. However, she does advise that if you want to target a market for studies, the best approach is to have people on the ground, in country, and listening so as to best understand the needs of that region. For Novartis, entering into frontier markets includes treating the markets individually, hiring locally, and providing new hires with the necessary support and training. In addition, Novartis likes to bring in expatriates so as to have a quick impact to the business unit by accelerating Novartis knowledge transfer to local talent. Expats also bring different perspectives from how trials are conducted in other markets, for example teaching the CRAs (clinical research associates) that a trial is a true partnership between the institution and the company, requiring time and effort on both parts.

Finally, the Novartis approach to frontier market clinical development includes strategic collaboration. Novartis has found that strategic collaborations with local and regional vendors help to establish and train centers more quickly and also give the company a better understanding of how clinical trials are conducted in these markets. 

Being a large multinational company with a long history, Novartis likes to partner with companies with which it has a track record. This might not be possible in frontier markets. In these cases, the company uses an assessment questionnaire to make sure the vendor or local CRO can comply with international standards. Barker urges caution in selecting strategic partners. “Don’t ship a huge consignment of a very expensive experimental cancer drug to a partner you have never used before,” she states. “This is a sensible approach in any country. We need to be extra vigilant as we strive to ensure the safety of our products and patients at all times. It’s common for samples to either be left on a quayside when the customs paperwork is not filled in properly or simply ‘disappear’ before they ever get to a patient.” Also, ensure the partner has the equipment necessary to store the drug properly, and for Phase 4 studies with registered products, determine if your product packaging meets the climate zone requirements. For example, a majority of Africa is in climate zone 4 — high humidity and very high temperature. “Many companies that are focused solely on the West in regard to commerce will just make and package their drugs to meet the stability requirements for climate zone 2,” Barker says. “Medicines which would be stable on your desk in an air-conditioned office in the United States may not be stable on a pharmacy shelf in a tropical climate zone, which may be a kiosk in the middle of the jungle or the corner of a desert.”

When considering developing your company’s frontier market-entry strategy for conducting clinical trials, Barker endorses thoroughly understanding disease epidemiology, unmet medical need, regulatory requirements, affordability, and genetic and disease diversity. For example, the pathogenesis of hypertension in black patients is thought to be different than in white patients. Thus, some hypertension drugs may work better in one population versus another. Dosages may vary among populations, with some needing more or less of a medicine to get the same therapeutic benefit, which is why Novartis performs global studies to ensure the “generalizability” of its data and the safe global use of its medicines. In Africa, some people may get their wages on a daily basis. So, not only do the drugs need to meet genetic and disease diversity, but also packaging may need to be such that patients can buy a two-to-three-day supply. According to Barker, the medicines Novartis studies and intends to bring to market in Africa need to be suitable for both global and local use. “We don’t do studies for any drugs that we are not going to commercialize in that country.  By increasing clinical trials in Africa, we want to make a difference for these patient populations by addressing their unmet medical needs.”