‘’IPAQT is now seen as a novel market-shaping business model to increase access to quality diagnostics’’

What was the driving force behind the IPAQT initiative? How did you get the various partners together to realise this goal? What were the challenges and the targets set?

Madhukar Pai

India is the highest TB burden country in the world. While the Revised National Tuberculosis Control Programme (RNTCP) is considered a success, only about 50 per cent of the TB patients are managed in the public sector. The remainder are managed in the largely unregulated private sector, mostly their first choice. Even as timely and accurate diagnosis is important for TB control, the private sector ecosystem is sub-optimal in this respect. There is overuse of unreliable tests, low availability and high cost of quality-assured diagnostics, lack of awareness about WHO-endorsed tests, and commercial incentives that result in cost inflation to patients. These factors result in high costs of care, delayed case finding, misdiagnosis and mistreatment, and emergence of TB drug resistance.

In May 2012, after concerted efforts by various stakeholders, the Indian government banned the use of sub-optimal serological, antibody tests that accounted for a big fraction of TB tests in the private sector [See story http://pharma.financialexpress.com/latest-issue/669-beyond-the-ban]. This provided a window of opportunity to promote the use of WHO-endorsed quality tests such as GeneXpert, Line Probe Assay and liquid cultures. However, the high prices of WHO endorsed tests (~ USD 60 to 100) in the private sector put them beyond the reach of the majority of TB patients. So, it was challenging for the market to replace the banned tests with higher quality, WHO-endorsed tests.

To address this market problem, the Clinton Health Access Initiative (CHAI) conducted an in-depth market analysis to make a case on the commercial potential of the Indian TB diagnostics market which was largely untapped and highlighted to suppliers of WHO-endorsed tests that high price was one of the biggest barriers to market penetration. CHAI engaged in negotiations with these suppliers (namely Cepheid Inc for GeneXpert, Biomerieux for Hain LPA and BacT/Alert, and BD for MGIT Liquid Culture) to make these quality tests available to the private sector at the same input price as the public sector. Instead of premium pricing, diagnostic companies were encouraged to consider the high-volume, low-margin model that is more appropriate for TB patients in the Indian context.

Furthermore, in order to reduce the mark-ups in the supply chain, CHAI helped organise a group of major laboratories into a partnership called IPAQT. IPAQT would deliver these tests at almost half the prevailing market prices by offering tests to the laboratories at lower input prices and capping the laboratory and provider margins per unit. The objective was to create a system wherein all the private intermediaries in the value chain gain in terms of greater absolute profits due to higher volumes, and hence would actively invest in driving widespread uptake of the WHO-endorsed tests to achieve higher volumes and therefore financial returns and health impact.

Furthermore, participating laboratories have committed to abide by certain guiding principles, which inter alia include, offering the tests at or below agreed upon ceiling price to the patients (which have to be transparently advertised), discontinuing use of sub-optimal blood TB tests, and notifying all TB cases to the RNTCP so that a linkage to quality treatment could be established. Adherence to these guiding principles is monitored. So, IPAQT hopes to create a sustainable “win-win-win” situation where patients, the RNTCP, laboratories and test manufacturers all benefit.

How long has the initiative been operational in India now? What are the milestones achieved so far?

The partnership, named “Initiative for promoting Affordable and Quality TB Tests” or “IPAQT”, came into being in April 2013 when the first set of private laboratories purchased GeneXpert and Hain LPA at negotiated prices. The number of GeneXpert tests and Hain LPAs used in the private sector in IPAQT’s first year (April 2013 to March 2014) is over 40,000 tests, up from less than 2000 tests during the whole of 2012.

How subsidised are the tests? What is the current price at which they are available as a part of IPAQT? Are the prices slated to come down any further? When the price of the GeneXpert cartridge is set at $10, how come the tests cost Rs 2000?

WHO-endorsed tests are available at IPAQT labs at prices 30-50 per cent lower than at non-IPAQT labs. The four WHO-endorsed tests are priced at:

• Xpert MTB/RIF – Rs 2000;
• Hain Genotype MTBDRplus line probe assay –Rs 1600;
• MGIT Liquid Culture – Rs 900 (for detection);
• BacT/Alert Liquid Culture – Rs 900 (for detection)

Patients and physicians can find out where to get these tests on the “Find a Lab” section of the IPAQT website (http://www.ipaqt.org/test-find-a-lab/).

Yes, the public sector price for a GeneXpert cartridge is $9.98. But this is just the cost of the reagents. It does not include transport and shipping costs, import duty and customs, distributor costs and margins, sales taxes, and costs incurred by the labs (e.g. amortisation of the equipment, lab overheads, personnel), and lab profit margins. When IPAQT was launched, the price of GeneXpert was Rs 1700, but had to be increased to Rs 2000 in 2014 because of significant devaluation of the rupee against the US dollar.

Further, price reductions may be possible, if the Government of India exempts all WHO-endorsed TB tests from import duties. This is something that civil society and stakeholders have been expecting. Since TB kills nearly 900 Indians every day, all TB products should be exempt as ‘life-saving’ drugs/devices.

How many labs in India are currently offering these tests? By how much has the number increased since the beginning of the initiative? What quality standards do the labs need to meet in order to offer the tests? Also, since reference labs under the RNTCP programme are also offering the tests are they also adhering to these standards?

Since its inception in 2013, when 15 labs came together to partner with the project, IPAQT has grown to include 65 member laboratories (as of April 2014), which includes five of six national laboratory chains, 22 hospital labs, and over 25 regional laboratory chains; these member labs collectively account for over 3500 collection centres, covering approximately 70 per cent districts in India.

To be eligible to join IPAQT, labs have to fulfill certain accreditation and quality standards. For the Hain Line Probe Assay and liquid cultures, only laboratories with Microbiology departments that are accredited by the National Accreditation Board for Laboratories (NABL) and/or College of American Pathologists (CAP) and/or RNTCP are eligible to join IPAQT. For GeneXpert, any kind of NABH, NABL accreditation and/or CAP and/or RNTCP accreditation is sufficient. Also, all member labs have to agree to external quality assurance (EQA). RNTCP accredited culture and drug-susceptibility testing labs also have to meet stringent quality standards and participate in EQA.

The number of GeneXpert tests and Hain LPAs used in the private sector in IPAQT’s first year (April 2013 to March 2014) is over 40,000 tests, up from less than 2000 tests during the whole of 2012.

This is much higher than it was before IPAQT was formed.

What are the current awareness levels on the availability of these tests? What is being done to increase the awareness and hence expand the reach and impact of the programme? Are doctors recommending any other tests apart from the WHO approved tests? If yes, why?

Low awareness of quality TB tests amongst private providers remains a key barrier to their widespread adoption. Although serological tests were banned by the government, the awareness about the ban at the grass root level is limited. Also, since the ban on serology, other sub-optimal tests such as in-house polymerase chain reaction (PCR) and interferon-gamma release assays (IGRAs) are popular in the private sector. In-house PCR can produce highly inconsistent results across labs, while IGRAs are blood tests that should be restricted to latent TB diagnosis (they are discouraged by WHO and RNTCP for active TB diagnosis).

CHAI conducted a survey among 1244 providers across 15 Indian states in early 2013 where diagnostic and treatment behaviour of privately practicing physicians was assessed. This survey revealed that ~85 per cent of the questioned providers were not aware of WHO-endorsed molecular tests. In addition, current market structure and dynamics thereof imply that all private intermediaries including private providers, collection centres and reference labs make higher per unit margins on ineffective tests such as IGRAs and in-house PCRs. Hence, they have a very strong incentive to keep promoting the use of such tests over the quality, WHO-approved tests.

Thus, marketing efforts of the labs alone are not sufficient to achieve improved awareness and prescription of quality TB diagnostics by private providers. These efforts need to be supported by targeted activities by CHAI and other partner NGOs. Over the last six months, CHAI has conducted a series of Continuing Medical Education (CMEs) sessions to sensitise providers on appropriate diagnostics and correct treatment as per International and Indian standards of TB Care; these are supplemented with collaborative activities of other NGOs. The team is also exploring the possibility of having a field force in certain cities to sensitise private sector providers on a one-on-one basis.

How could using these tests for fresh cases as opposed to only for retreatment cases (as in RNTCP labs) help increase the rate of diagnosis of TB? Is there currently a protocol on which patients should be suggested a particular test?

According to the International Standards for TB Care (3rd Edition, 2014): “All patients (including children) who are suspected of having pulmonary tuberculosis and are capable of producing sputum should have at least two sputum specimens submitted for smear microscopy or a single sputum specimen for Xpert MTB/RIF testing in a quality-assured laboratory. Patients at risk for drug resistances, who have HIV risks, or who are seriously ill, should have Xpert MTB/RIF performed as the initial diagnostic test. Blood-based serologic tests and interferon gamma release assays should not be used for diagnosis of active tuberculosis.”

Since Xpert MTB/RIF is more sensitive than sputum smears (sensitivity of Xpert is about 98 per cent in smear-positive TB cases, and 67 per cent in smear-negative cases), if it is used on new patients with TB symptoms, then it can pick up more cases of TB than smears, and do it within a short time (results are available the same day). If Xpert MTB/RIF is used on retreatment or treatment failure cases, then it can rapidly diagnose MDR-TB by detecting rifampicin resistance within the same day. Resistance to rifampicin is a very good marker of MDR-TB. So, Xpert MTB/RIF can help to immediately start MDR-TB therapy, while waiting for confirmation using liquid culture and drug-susceptibility testing.

How many fresh cases of TB, MDR and others have been detected so far through IPAQT? Have these cases been notified to RNTCP, what is the process for that?

Despite notification of TB patients diagnosed in the private sector being made mandatory by the government in May 2012, currently very few TB patients diagnosed in the private sector are notified to the government. The reasons for low case notifications range from labs and doctors not recording patient information, private laboratories and hospitals not being aware of the notification process (who to notify to, format and frequency etc.). Lastly, the government systems are not fully established and enabled to receive case notifications through automated methods (e.g. remote connectivity software that can be connected to GeneXpert machines and computers).

Even though the IPAQT charter requires all member labs to notify positive TB cases to the respective district TB officers, all stakeholders are experiencing operational challenges – the private sector (labs and providers) are unsure about how best to collect patient data while respecting privacy, and to notify, and about what happens to the patient data after notification. On the other hand, RNTCP is grappling with the question of how best to follow up on the notification data received so as to not alienate the private sector.

The methodology for notification from private sector ranges from paper forms submitted to the DTO on a daily basis, to weekly emails. In a subset of 14 IPAQT labs where 9,506 samples have been tested, 2,868 positive TB cases and 711 MDR-TB cases have been detected. Efforts are ongoing to install remote connectivity software to all IPAQT labs, and to link them to the RNTCP notification portal called Nikshay http://nikshay.gov.in/User/Login.aspx. Hopefully, these efforts will result in many more private cases being notified.

How do you see such public private models further being able to create more impact? What advantages do they offer and what remain the challenges? Could they be for profit going forward?

Ultimately, TB patients need a complete solution to their problem, regardless of whether they seek care in the public or the private sector. Therefore, it is important for the private sector to work hand in hand with the RNTCP, and improve the overall quality of TB care in the country. IPAQT has shown that the private for-profit sector (laboratories as well as diagnostic companies) is interested and willing to consider novel business models that can increase their volumes (hence make economic sense, and are sustainable), as well as contribute to a national public health effort.

IPAQT is now being seen as a novel market-shaping business model to increase access to quality diagnostics to patients in the private sector. While IPAQT has demonstrated that it is possible to engage diagnostic manufacturers and laboratories to serve a public health need, it faces many challenges. To reach scale in a country of India’s size, will require many more labs to come forward and join the initiative. It will require doctors in India to prescribe only WHO-endorsed, high-quality TB tests and adhere to national and international standards for TB care. It will require RNTCP to accept notifications from IPAQT labs and set up systems to link MDR-TB cases to free second-line treatment.

Even if the above were to be met, prices of TB tests are still too high for the base of the pyramid (BOP). We need new TB tests that are as accurate as the currently available WHO-endorsed tests, but much cheaper. Such technologies are under development or evaluation, including products from India, and will have a big potential market. We recently estimated that a $5 molecular rapid test for TB that can replace sputum smears will have a potential annual market of $154 million in 22 high burden countries. http://tbevidence.org/wp-content/uploads/2014/02/Kik-EJR-2014.pdf

Is IPAQT also looking at other countries with high TB burden to implement such a model or to tweak it? What goals have been set for this year for India?

While there is merit in replicating the IPAQT model in other countries which are characterised by high disease burden and large private sectors, the immediate goal of IPAQT is to reach some scale in India and demonstrate that the model is feasible and has impact. India has about 400 NABL accredited labs and IPAQT is hoping many of them will join the initiative and support TB control in India.

Accurate diagnosis alone is not enough – we need to make sure that all diagnosed cases get notified and treated with appropriate drug regimens and treatment completion is ensured. So, CHAI is working with the RNTCP and has identified laboratories in a few geographical areas to develop systems and processes for accurate patient data recording, and development and strengthening of the RNTCP systems for the notification process and linkages to MDR-TB treatment in the public sector.

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