India and drug safety : Latest PVig attempt showing promise

India seems to be making slow but sure progress towards reversing its abysmal track record in pharmacovigilance – medical jargon for monitoring the safety of marketed medicines. The country has reported 33,702 adverse drug reactions (ADRs),  side-effects arising from a host of marketed drugs, as of December 21, 2012,  according to data shared by the National Coordinating Centre for Pharmacovigilance Programme of India (NCCPVP) with Apothecurry. These reports have been submitted to the World Health Organisation’s Uppsala Monitoring Centre (UMC) which maintains a global database of ADRs.

This is a record of sorts. India began reporting ADRs to the UMC in 1998 but the numbers were paltry. By 2005, it had managed less than 400 such reports suggesting a feeble attempt at capturing the true extent of ADRs in the country. Between 2005 and 2007, zero ADRs were recorded from India in the UMC database though a new national programme had been launched by then.

The latest number has been totted up since April 2011 when the ministry of health, in possibly its fourth attempt to create a meaningful drug safety programme for the country, entrusted responsibility to the Indian Pharmacopoeia Commission which functions as the NCCPVP.

The NCCPVP is the nodal centre that receives ADR reports from 60 hospitals all over the country that are functioning as ADR monitoring centres. “The number of reports has been constantly on the rise,” said an official with the NCCPVP who requested not to be identified.

Risk vs benefit

No drug is free from side-effects. Regulators approve a drug when its benefits are shown in clinical trials to outweigh its risks.  A good example is cancer chemotherapy – drugs that weaken the immune system but are potent weapons against cancer cells.

Since trials are conducted on a limited number of subjects, new side-effects may come to light or the degree of known side-effects may be found to occur beyond acceptable limits only after a drug is mass-marketed and consumed by large numbers over a period of time.

Instances of popular drugs that were later withdrawn for safety reasons are diabetes drug rosiglitazone, painkiller rofecoxib and diet drug combination “fen-phen” (fenfluramine/phentermine). All three were withdrawn for their adverse impact on the heart. There are several others.

ADRs are recognised to be a leading cause of death, globally.

Continuous challenge

World over, drug safety monitoring has proved to be a challenging task since it relies heavily on sponataneous reporting by the medical community and drug companies. Neither source has been found to be entirely consistent nor reliable either due to the lack of time, awareness, or intent.

Regulators, especially in countries such as the US with a relatively strong ADR reporting culture, have also come under fire for ignoring or not moving fast enough to process the reports that they do receive, thus failing to recognize early warnings and preventing fatalities.

Countries have been improving upon their rules and systems. In 2008, the US set up the Sentinel Initiative, an electronic system, with a view to rapidly analysing reports so as to capture early warnings or signals.  In 2011, China revised its ADR reporting rules.  Last year, the Indian drugs regulator threatened to cancel licences if companies failed to submit drug safety reports. This followed an investigation by a committee of Parliamentarians that showed that companies were openly flouting rules requiring them to submit periodic safety updates on new drugs.

India, a laggard

For years, drug safety experts from within and outside the country have remarked at the sorry state of pharmacovigilance in a country that lays claim to being the world’s fourth-largest pharmaceutical market by volume. India has lagged behind other emerging markets such as China, Malaysia and Thailand. For instance, in 2010, China reported 6,90,000 ADRs.

India relies heavily on signals from western countries to approve or ban medicines. However, this approach precludes the impact of genetic, ethnic and other differences that might heighten or dampen the occurence of specific side-effects.

India’s large traditional and herbal medicines industry which often escapes stringent rules targeted at modern medicine is seen as another reason why it needs its own drug safety monitoring.

The current programme builds on an earlier one that was kickstarted in 2004 but was canned for want of funding, among other things. Many of the the ADR reporting centres identified under that programme continue to operate.  There are some important differences, however.

One, while the 2004 project received limited-duration funding from the World Bank, this one is funded by the ministry of health suggesting sustainability and commitment. Two, while earlier the thousands of suspected ADRs captured by various centres remained on paper, they are now entered directly into the UMC’s Vigibase database.

“It is definitely better than before,” says Dr Urmila Thatte, head of the department of clinical pharmacology at Mumbai’s KEM Hospital and member of the Working Group of the National Pharmacovigilance Programme.  “The IPC has people dedicated to the programme who are working to review all the data.” She added that an important objective, that of creating a culture of reporting, was being slowly achieved.

Early rewards

It is by no means an easy task. Centres have to constantly reach out to stakeholders through seminars, workshops, training programmes and so on.  A sample of the nodal centre’s periodic newsletters that carry updates can be found here.

But some early gains have been made. In the last six months, the NCCPVP has been able to aid CDSCO, India’s drug regulator by sharing India-specific ADR reports on drugs such as painkiller analgin, diabetes drug pioglitazone and muscle relaxant tolperisone which were the subjects of warning letters or label changes globally, the official said. “This is clearly an achievement,” this official said.

The programme is on course to being expanded. Another 30 institutions are expected to  join it thus taking the total number of monitoring centres to 90 in a month or two, the official said.

The biggest challenge to the rapid scale-up of this programme would be creating awareness and sustained interest in ADR reporting among medical professionals and other stakeholders such as chemists who are often the first port of call for patients with common aches and pains, minor infections and low-grade fevers.

The other would be to include the vast private hospital sector in ADR monitoring. Currently most of the ADR monitoring centres are government-owned hospitals. Yet, expensive new drugs – the ones whose track record is still being established in clinical practice- are more likely to be prescribed in private facilities.

Pic courtesy photostream of Doug88888 on Flickr