Reinstating its commitment to ensure high quality healthcare services to patients across the spectrum, the central government has set apart Rs.5000 crore for the All India Institute of Medical Sciences (AIIMS). Apart from that, the government also announced its decision to set up four new AIIMS in Andra Pradesh, West Bengal, Maharashtra and Uttar Pradesh.
From the allotted funds Rs.900 crore will be dedicated for each AIIMS to be functional at the earliest. The government also informed that the six new AIIMS like institutions situated in Bhopal, Patna, Jodhpur, Rishikesh, Raipur and Bhubaneswar have already started its functions and that in the future they plan to add one AIIMS like institution in each of the states.
While delivering his maiden budget, finance minister Arun Jaitley announced that they will provide free drug and diagnostic services to needy patients along with establishing 12 new government medical colleges plus dental facilities across the country. To ensure availability of high quality drugs to the patients the Center will be providing funds to set up new drugs and food testing labs across the country apart from supporting with funds to modernise and technically upgrade the 31 existing labs. The Centre for the first time has decided to set up 15 new rural healthcare regional centers to address the lacunae in addressing the healthcare needs of the patients in the far-flung region of the country.
With a view to inspire and encourage new entrepreneurs to take up good projects, the government has set up a committee for MSME and has allocated Rs.10,000 crore for the same. Further the FM promised to set up three dedicated biotechnology parks in Pune, Kolkatta and Mohali through the public private partnership (PPP) route and stressed that there needs to be more PPP with private and foreign institutes to encourage biotechnology in the country.
Single Ascending Dose
Single ascending dose studies are those in which small groups of subjects are given a single dose of the drug while they are observed and tested for a period of time. Typically, a small number of participants, usually three, are entered sequentially at a particular dose. If they do not exhibit any adverse side effects, and the pharmacokinetic data is roughly in line with predicted safe values, the dose is escalated, and a new group of subjects is then given a higher dose. If unacceptable toxicity is observed in any of the three participants, an additional number of participants, usually three, are treated at the same dose.This is continued until pre-calculated pharmacokinetic safety levels are reached, or intolerable side effects start showing up (at which point the drug is said to have reached the maximum tolerated dose (MTD)).
Example: Single Ascending Dose First-in-Human Study of a Novel Ant malarial Drug (CDRI 97/78)
The starting dose was 80 mg; calculation of starting dose was based on the basis of maximum tolerated dose of 100 mg/kg obtained in rats. This was used to obtain a dose of 96 mg for a 60 kg man. The formulation which was available for a dose below this was of 80 mg and hence taking these factors into consideration a starting dose of 80 mg was chosen. The following dose levels were evaluated: 80, 160, 320, 400, 500, 600, and 700 mg. The starting dose was calculated by allometric scaling from animals. At each dose level, volunteers were assessed before proceeding to the next dose. The decision to dose only 2 volunteers was taken, after analysis of data of 600 mg, wherein no remarkable adverse events were noted.
The decision to stop the dose escalation was based on the appearance of the dose limiting toxicity (DLT) which was defined as the dose at which any of the following appeared: severe nausea, vomiting, heartburn, headache, remarkable change in vital parameters such as blood pressure, heart rate, respiratory rate or oxygen saturation of blood, changes in QT interval, or any event that in the opinion of the investigators required stopping of the trial.
Multiple Ascending Dose:
Multiple ascending dose studies (MAD) are designed to test the pharmacokinetics and pharmacodynamics of multiple doses of the experimental drug. A group of subjects receives multiple doses of the drug, starting at the lowest dose and working up to a pre-determined level. At various times during the period of administration of the drug, and particularly whenever the dose is increased, samples of blood and other bodily fluids are taken. These samples are analysed in order to determine how the drug is processed within the body and how well it is tolerated by the body.
Pharma cos & CROs opt for cloud computing to propel competence in data integration for clinical studies
Indian pharma and clinical research organisations (CROs) are adopting cloud technology solutions to accelerate drug development, enable data compilation, create efficiency and decrease the time-to market. Following changes on the global regulatory landscape, there is an increased dependence on reliable data which has led pharma companies and CROs opt for cloud computing to nurture innovation and improve productivity, according to industry experts.
A recently concluded DIA workshop on ‘Evolving landscape of clinical data management: Focus on technology and data standard’ indicated that in the current competitive landscape, pharma industry was looking to collaborate with the clinical data management service providers to garner regulatory compliance and improve efficiency.
“Clinical research business in the country is on a revival mode and is indicating signs of growth. But the momentum of growth is still found wanting even though change is evident and perceptible. The focus is not on just clinical data management (CDM) but a shift to value-added services like medical monitoring and safety data processes. Now this will see India play a big role in the space of clinical data management projects”, Suresh Ramu, chief executive officer, Cytespace told Pharmabiz on the sidelines of the DIA workshop.
“However, the growth in clinical research particularly human studies is not exponential but steady. The way forward is mergers and acquisitions with the industry moving to a consolidation mode”, noted the Cytespace chief executive officer, in his keynote address on the ‘Interplay of technology and data standards in CDM’.
There are clear signs that global majors have recognised the indispensability of India. This has led pharma and the CROs to move on to cloud computing and analytics platforms to reduce manual errors and help achieve better quality and patient safety. Since clinical trials are a critical component of drug development, there is need to achieve seamless integration across applications to diminish data duplication, highlighted experts at the DIA workshop.
The participants like clinical data managers, clinical database programmers, bio statisticians, besides related professionals were given a lucid angle on the role of cloud technology as an innovative tool for clinical data management.
Mandar Ghatnekar, senior manager, Life Sciences Practice, Accenture in his presentation on the recent innovations in technology solutions for clinical data management said that the focus of pharma industry and the CROs was to achieve speed, functionally and collaboration. Technology trends like social media, mobility, analytics and cloud computing (SMAC) are evolving in this space.
“Particularly, cloud computing and analytics have created a seamless and scalable environment. The industry be it pharma or CROs are now seen to increasingly invest in such technologies to achieve speed to market,” he added.
A few years ago, global pharma companies were reluctant to host any data of clinical trial on an external environment. But today, all these companies and those in India are looking to increase their presence on a private cloud environment. The focus of information technology majors including SAP and Oracle is to develop life sciences software powered by analytical tools and reporting applications to enhance knowledge management, said Ghatnekar.
Kerala would get the distinction to be the first state in the country to have pharmacy inspectors in all the districts of the state for strict enforcement of Pharmacy Act 1948. Currently, there are five pharmacy inspectors working in the state, while the government has accorded sanction to appoint nine more pharmacy inspectors.
The state government had last year accorded sanction to appoint seven more pharmacy inspectors on a proposal submitted by the Kerala State Pharmacy Council (KSPC), in addition to the five pharmacy inspectors currently working in the state to detect cases of violation of Pharmacy Act. Two posts were lying vacant for some time. All these nine inspectors are likely to be appointed by the end of the year as per the request by KSPC to the state health department.
After these appointments, Kerala would get the distinction to be the first state in the country to have pharmacy inspectors in all the districts for strict enforcement of Pharmacy Act 1948. KSPC is a statutory body functioning under the Kerala State Health Department. It is constituted under Section 19 of the Pharmacy Act, 1948 to regulate the profession and practice of pharmacy in the state.
According to the state council officials, the appointment of pharmacy inspectors will be helpful in carrying out timely inspections for effective check on illegal activities like dispensing of medicines by unqualified people. Informs B Rajan, president, KSPC, “Pharmacy Inspectors are appointed on a part-time basis from among the pharmacists of state government healthcare institutions who are supposed to carry out inspections in retail and government drug stores for the stipulated six day period in a month and then submit the inspection reports to the state council for further action.”
An honorarium is being paid to the pharmacy inspector from the funds generated through registrations by the state council. Until 2006, the council had seven inspectors with charges of two districts for one inspector but as of today two posts are lying vacant which are likely to be filled by September, 2014. Kerala has a total of 14 districts.
The council is a quasi-judicial body which can act against pharmacists by way of either issuing warning letters or canceling their registrations. Council can also take action against the offenders for violation of the Pharmacy Act under Section 36 wherein the executive committee of the state council can give the judgment based on the inspection report filed by the state Food and Drug Administration (FDA) official, oath of affidavit and explanation by the pharmacist.
SINGLE ASCENDING DOSE studies are those in which small groups of subjects are given a single dose of the drug while they are observed and tested for a period of time. Typically, a small number of participants, usually three, are entered sequentially at a particular dose. If they do not exhibit any adverse side effects, and the pharmacokinetic data is roughly in line with predicted safe values, the dose is escalated, and a new group of subjects is then given a higher dose. If unacceptable toxicity is observed in any of the three participants, an additional number of participants, usually three, are treated at the same dose. This is continued until pre-calculated pharmacokinetic safety levels are reached, or intolerable side effects start showing up (at which point the drug is said to have reached the maximum tolerated dose (MTD)). MULTIPLE ASCENDING DOSEstudies are conducted to better understand the pharmacokinetics and pharmacodynamics of multiple doses of the drug. In these studies, a group of patients receives multiple low doses of the drug, while samples (of blood and other fluids) are collected at various time points and analyzed to acquire information on how the drug is processed within the body. The dose is subsequently escalated for further groups, up to a predetermined level.
FIRST-IN-HUMAN SINGLE ASCENDING DOSE ESCALATION DESIGNS
In contrast to traditional dose escalation designs, where for example, cohorts of subjects are allocated to ascending doses (and placebo) until a maximum tolerated dose (MTD) is empirically determined, the continual reassessment method (CRM) models the dose- and/or exposure-toxicity relationship to focus on the identification of the dose-range of interest near the MTD and for this to be explored further. These adaptive dose escalation designs can be expanded to also efficiently establish proof-of-mechanism or proof-of-target modulation, if validated biomarker endpoints are available. The traditional First in Human study objectives of safety and tolerability can be extended to include an assessment of proof-of-mechanism in the very first study conducted with the investigational compound. The ability to assess proof-of-mechanism in this early developmental setting provides an opportunity to greatly enhance the clinical development strategy for the compound. The adaptation is intended to quickly hone in on the predicted dose-range of interest. is avoids the risks associated with exposing patients in an in effective low dose range, whilst minimizing exposure to high doses with an unacceptable tolerability and safety profile.
SEAMLESS MULTIPLE ASCENDING DOSE AND PROOF-OF-CONCEPT STUDY DESIGNS
The objective of seamless multiple ascending dose and proof-of-concept studies is to combine a multiple ascending dose (MAD) study in patients with the proof-of-concept of the investigational compound.