Compensation in Neonatal Clinical Trials: A Perspective.

Well conducted clinical trials are the mainstay for generating evidence on preferred treatments. In order to adequately protect the interests of the trial participants, the Central Licensing Authority of India has formulated guidelines to determine the quantum of compensation in cases of regulatory clinical trial related injury or death. However, these guidelines do not address the nuances of trials recruiting children aged under 16 years, within which, neonates are the most vulnerable population. Thus, there is a need for addressing this lacuna in the current guidelines. This article examines the challenges in determining the quantum of compensation in neonatal clinical trials using the current formula, which is a corollary to the challenges faced by the authors in procuring clinical trial insurance for the Probiotic supplementation for Prevention of Neonatal Sepsis (ProSPoNS) trial. Further, it suggests a template for a differential formula using birthweight of infants, which is one of the many important factors impacting neonatal mortality.

Study protocol for economic evaluation of probiotic intervention for prevention of neonatal sepsis in 0-2-month old low-birth weight infants in India: the ProSPoNS trial.

INTRODUCTION: The ProSPoNS trial is a multicentre, double-blind, placebo-controlled trial to evaluate the role of probiotics in prevention of neonatal sepsis. The present protocol describes the data and methodology for the cost utility of the probiotic intervention alongside the controlled trial. METHODS AND ANALYSIS: A societal perspective will be adopted in the economic evaluation. Direct medical and non-medical costs associated with neonatal sepsis and its treatment would be ascertained in both the intervention and the control arm. Intervention costs will be facilitated through primary data collection and programme budgetary records. Treatment cost for neonatal sepsis and associated conditions will be accessed from Indian national costing database estimating healthcare system costs. A cost-utility design will be employed with outcome as incremental cost per disability-adjusted life year averted. Considering a time-horizon of 6 months, trial estimates will be extrapolated to model the cost and consequences among high-risk neonatal population in India. A discount rate of 3% will be used. Impact of uncertainties present in analysis will be addressed through both deterministic and probabilistic sensitivity analysis. ETHICS AND DISSEMINATION: Has been obtained from EC of the six participating sites (MGIMS Wardha, KEM Pune, JIPMER Puducherry, AIPH, Bhubaneswar, LHMC New Delhi, SMC Meerut) as well as from the ERC of LSTM, UK. A peer-reviewed article will be published after completion of the study. Findings will be disseminated to the community of the study sites, with academic bodies and policymakers. REGISTRATION: The protocol has been approved by the regulatory authority (Central Drugs Standards Control Organisation; CDSCO) in India (CT-NOC No. CT/NOC/17/2019 dated 1 March 2019). The ProSPoNS trial is registered at the Clinical Trial Registry of India (CTRI). Registered on 16 May 2019. TRIAL REGISTRATION NUMBER: CTRI/2019/05/019197; Clinical Trial Registry.

Identification of publicly available data sources to inform the conduct of Health Technology Assessment in India.

Background: Health technology assessment (HTA) provides a globally-accepted and structured approach to synthesising evidence for cost and clinical effectiveness alongside ethical and equity considerations to inform evidence-based priorities. India is one of the most recent countries to formally commit to institutionalising HTA as an integral component of the heath resource allocation decision-making process. The effective conduct of HTA depends on the availability of reliable data.   Methods: We draw from our experience of collecting, synthesizing, and analysing health-related datasets in India and internationally, to highlight the complex requirements for undertaking HTA, and explore the availability of such data in India. We first outlined each of the core data components required for the conduct of HTA, and their availability in India, drawing attention to where data can be accessed, and different ways in which researchers can overcome the challenges of missing or low quality data. Results: We grouped data into the following categories: clinical efficacy; cost; epidemiology; quality of life; service use/consumption; and equity. We identified numerous large local data sources containing epidemiological information. There was a marked absence of other locally-collected data necessary for informing HTA, particularly data relating to cost, service use, and quality of life. Conclusions: The introduction of HTA into the health policy space in India provides an opportunity to comprehensively assess the availability and quality of health data capture across the country. While epidemiological information is routinely collected across India, other data inputs necessary for HTA are not readily available. This poses a significant bottleneck to the efficient generation and deployment of HTA into the health decision space. Overcoming these data gaps by strengthening the routine collection of comprehensive and verifiable health data will have important implications not only for embedding economic analyses into the priority setting process, but for strengthening the health system as a whole.

Research protocol for an epidemiological study on estimating disease burden of pediatric HIV in Belgaum district, India.

BACKGROUND: Pediatric HIV is poised to become a major public health problem in India with the rising trend of HIV infection in pregnant women (Department of AIDS Control, Ministry of Health and Family Welfare, http://www.naco.gov.in). There is lack of information on the epidemiology of pediatric HIV infection in India. Existing surveillance systems tend to underestimate the Pediatric burden. The overall aim of the present study is to estimate the disease burden of pediatric HIV among children in Belgaum district in the state of Karnataka in Southern India. An innovative multipronged epidemiological approach to comb the district is proposed. METHODS: The primary objectives of the study would be attained under three strategies. A prospective cohort design for objective (i) to determine the incidence rate of HIV by early case detection in infants and toddlers (0-18 months) born to HIV infected pregnant women; and cross sectional design for objectives (ii) to determine the prevalence of HIV infection in children (0-14 years) of HIV infected parents and (iii) to determine the prevalence of HIV in sick children (0-14 years) presenting with suspected signs and symptoms using age specific criteria for screening. Burden of pediatric HIV will be calculated as a product of cases detected in each strategy multiplied by a net inflation factor for each strategy. Study participants (i) (ii) (iii): HIV infected pregnant women and their live born children (ii) Any HIV-infected man/woman, of age 18-49 years, having a biological child of age 0-14 years (iii) Sick children of age 0-14 years presenting with suspected signs and symptoms and satisfying age-specific criteria for screening. Setting and conduct: Belgaum district which is a Category 'A' district (with more than 1 % antenatal prevalence in the district over the last 3 years before the study). Age-appropriate testing is used to detect HIV infection. DISCUSSION: There is a need to strengthen existing pediatric HIV estimation methods in India and other developing countries. We hope that the novel methodology emanating from this study would be applicable for estimating the burden of HIV in other settings and it would be adaptable for estimating the burden of other infectious/chronic diseases. Findings from this study will give future direction to the national program for prevention and control of HIV in India and other developing countries.

Community and healthcare providers' perspectives on male circumcision: a multi-centric qualitative study in India.

BACKGROUND: Although male circumcision (MC) is recommended as an HIV prevention option, the religious, cultural and biomedical dimensions of its feasibility, acceptability and practice in India have not been explored till date. This study explores beliefs, experiences and understanding of the community and healthcare providers (HCPs) about adult MC as an HIV prevention option in India. METHODS: This qualitative study covered 134 in-depth interviews from Belgaum, Kolkata, Meerut and Mumbai cities of India. Of these, 62 respondents were the members of circumcising (CC)/non-circumcising communities (NCC); including medically and traditionally circumcised men, parents of circumcised children, spouses of circumcised men, and religious clerics. Additionally, 58 registered healthcare providers (RHCPs) such as general and pediatric surgeons, pediatricians, skin and venereal disease specialists, general practitioners, and operation theatre nurses were interviewed. Fourteen traditional circumcisers were also interviewed. The data were coded and analyzed in QSR NUD*IST ver. 6.0. The study has not explored the participants' views about neonatal versus adult circumcision. RESULTS: Members of CC/NCC, traditional circumcisers and RCHPs expressed sharp religious sensitivities around the issue of MC. Six themes emerged: Male circumcision as the religious rite; Multiple meanings of MC: MC for 'religious identity/privilege/sacrifice' or 'hygiene'; MC inflicts pain and cost; Medical indications outweigh faith; Hesitation exists in accepting 'foreign' evidence supporting MC; and communication is the key for acceptance of MCs. Medical indications could make members of NCC accept MC following appropriate counseling. Majority of the RHCPs demanded local in-country evidence. CONCLUSION: HCPs must educate high-risk groups regarding the preventive and therapeutic role of MC. Communities need to discuss and create new social norms about male circumcision for better societal acceptance especially among the NCC. Feasibility studies on MC as an individual specific option for the high risk groups in health care setting needs to be explored.

An update on second-generation devices for endometrial ablation.

Menorrhagia is a very common problem. Hysterectomy has been the traditional surgical treatment of choice guaranteeing amenorrhoea. It is 100% effective but is associated with surgical complications, and is more costly in terms of economic impact and recovery time. Minimally invasive procedures to ablate the endometrium reduce complications and recovery time. The newer second-generation endometrial ablation devices negate the need for surgery under direct hysteroscopic vision, thus ensuring that the treatments are not operator dependent. However, they heavily rely on the device themselves to ensure safety and efficacy. There are a variety of these devices currently available on the market. The authors will review these devices and provide the evidence for their suitability in various settings.

Costs of illness due to typhoid fever in an Indian urban slum community: implications for vaccination policy.

Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to facilitate the use of available anti-typhoid vaccines in developing countries. This one-year prospective surveillance was carried out in an urban slum community in Delhi, India, to estimate the costs of illness for cases of typhoid fever. Ninety-eight culture-positive typhoid, 31 culture-positive paratyphoid, and 94 culture-negative cases with clinical typhoid syndrome were identified during the surveillance. Estimates of costs of illness were based on data collected through weekly interviews conducted at home for three months following diagnosis. Private costs included the sum of direct medical, direct non-medical, and indirect costs. Non-patient (public) costs included costs of outpatient visits, hospitalizations, laboratory tests, and medicines provided free of charge to the families. The mean cost per episode of blood culture-confirmed typhoid fever was 3,597 Indian Rupees (US$ 1=INR 35.5) (SD 5,833); hospitalization increased the costs by several folds (INR 18,131, SD 11,218, p<0.0001). The private and non-patient costs of illness were similar (INR 1,732, SD 1,589, and INR 1,865, SD 5,154 respectively, p=0.8095). The total private and non-patient ex-ante costs, i.e. expected annual losses for each individual, were higher for children aged 2-5 years (INR 154) than for those aged 5-19 years (INR 32), 0-2 year(s) (INR 25), and 19-40 years (INR 2). The study highlights the need for affordable typhoid vaccines efficacious at 2-5 years of age. Currently-available Vi vaccine is affordable but is unlikely to be efficacious in the first two years of life. Ways must be found to make Vi-conjugate vaccine, which is efficacious at this age, available to children of developing-countries.