Case Studies

DATA ABSTRACTION AND CURATION

Parkinson’s disease (PD) is an incurable, chronic neurological disorder of largely unknown etiology, characterized by degeneration of dopaminergic neurons and the subsequent loss of dopamine throughout the brain. The symptoms of PD typically begin following the loss of 60–80% of the dopamine-producing cells in the brain, with symptoms continuing to worsen slowly over time. Advanced PD (APD) represents a progressed form of PD, characterized by symptoms that are refractory to best medical therapy (BMT). Treatment options for patients with APD who develop resistance to BMT are limited and consist mainly of three device-aided interventions: deep brain stimulation (DBS), levodopa/carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusion (CSAI).  Our client wanted to conduct a systematic literature review of on on the efficacy, safety, tolerability, and quality of life (QoL) of LCIG, CSAI, and DBS in advanced PD patients. In order to assist our client, we screened approximately 2285 studies for 1st pass and 190 studies for 2nd pass screening phase. Twenty nine articles were finally extracted and the findings of which helped the client in report writing.

Atopic dermatitis results when aberrant barrier function and immune activation occur within the skin. Standard therapies for atopic dermatitis have fallen short, prompting efforts to discover novel therapeutics for this disease. Of these, a particular human monoclonal antibody that inhibits the actions of both IL-4 and IL-13, has shown the greatest promise.  Clinical trials of systemic drug in moderate-to-severe atopic dermatitis have demonstrated marked improvement in patient symptoms, including pruritus and clinically visible disease. Our client wanted to conduct a systematic literature review of on efficacy, patient-reported and safety outcomes of this particular monoclonal antibody relative to conventional treatments for moderate-to-severe paediatric atopic dermatitis. In order to assist our client, we screened approximately 3600 studies for 1st pass and 180 studies for 2nd pass phase. Twenty three articles were finally extracted, findings of which helped us the client in report writing.

Premenopausal women with hormone receptor–positive (HR+) breast cancer are frequently under-represented in clinical trials, and treatment strategies in the premenopausal setting are usually extrapolated from data from postmenopausal patients. Our client wanted to conduct a systematic literature review of Clinical Trials in Premenopausal Women with Advanced HR+ HER2- Breast Cancer. We provided assistance by searching for relevant information from Ovid, followed by screening of approximately 521 studies for 1st pass and 42 studies for 2nd pass. Only 5 studies went through the data extraction phase. The data provided was utilised by the client to generate a systematic literature review on the said topic.

Gastric cancer is the third most common cause of cancer-related death across the world. Treatment of gastric cancer generally involves surgery followed by chemoradiation therapy or chemotherapy. Our client wanted to evaluate the safety and efficacy of commonly used chemotherapeutic medications for gastric cancer management. In order to assist our client to develop a systematic review on this topic we screened 3956 studies for 1st pass, 384 studies for 2nd pass, 6 conference abstracts (American Society of Clinical Oncology and European Society for Medical Oncology etc.) and finally we abstracted data from 45 studies.

Colorectal cancer is a malignant tumor arising from the inner wall of the large intestine (colon) or rectum and treatment primarily depends on the location, size, and extent of cancer spread, as well as the health of the patient. Surgery is the preferred treatment method. However, treatment of patients with nonresectable and resectable colorectal cancer at an advanced stage is challenging and necessitates the initiation of chemotherapy, use of signaling inhibitors and monoclonal antibodies (mAbs) that can extend life and improve quality of life of the patients. Our client wanted to develop a systematic literature review on the efficacy and safety of monoclonal antibodies in colorectal cancer management. We assisted with 1st pass screening of 1974 studies, 2nd pass screening of 142 studies and finally extracted data from 15 studies.

Disease-modifying antirheumatic drugs (DMARDs) are a group of drugs often used for the treatment of rheumatoid arthritis (RA) as they suppress overactive immune and/or inflammatory systems of the body. The choice of DMARD is dependent on a number of factors, such as the stage and severity of the joint disease, possible side effects, desired outcomes and patient preference. A systematic literature review was aimed to update the body of evidence on the use of DMARDs in RA. To cater to this objective, we provided the client with data that was extracted from 65 studies.

Asthma is a chronic lung disease that inflames and narrows the airways in the lungs and affects a significant proportion of individuals across the world. Our client wanted to examine the current prevalence and available treatment for this condition. We screened 4972 studies for 1st pass, 647 studies for 2nd pass and finally data was extracted from 75 studies. We also provided the client with a complete shell report of the findings on this topic that could be used to generate a systematic literature review on this topic.

Atopic dermatitis (AD), also known as atopic eczema, is a type of skin inflammation resulting in itchy, red, swollen, and cracked skin. It is a pruritic condition that is generally treated with immunosuppress agents. Our client wanted to design a systematic literature review on the role of systemic immunosuppressive therapy for the treatment of AD. We screened approximately 2983 studies for 1st pass, 245 studies for 2nd pass and subsequently extracted data from 47 studies. Additionally, we determined the risk of bias of the included studies using the Cochrane Risk of Bias Tool. The data provided to the client resulted in two systematic literature reviews on this topic.

Overactive bladder is a condition characterized by a sudden urge to urinate (urge incontinence) and may even lead to the involuntary loss of urine (urinary incontinence). It affects the social life of the patients. However, suitable evaluation can aid in determining the specific cause for overactive bladder symptoms. Our client wanted to develop a systematic literature review on patient-reported outcomes in overactive bladder. The primary focus was to understand the general perception of this condition and the need to determine the clinical effectiveness of available treatment regimes. We assisted the client with relevant data extraction from 5 studies.

Breast cancer is the most common cancer in women with more than a million affected individuals across the world. The choice of treatment majorly depends on the type and stage of breast cancer, age and overall health. Often patients are recommended to undergo systemic treatment with chemotherapy. Our client wanted to determine the safety and efficacy of existing chemotherapy for breast cancer. We provided assistance by searching for relevant information from PubMed, EMBASE and Cochrane, followed by screening of approximately 6452 studies for 1st pass, 686 studies for 2nd pass and finally extracted data from 98 studies. The data provided was to be used by the client to generate a systematic literature review on the said topic.

Diabetes Mellitus (DM) is a metabolic disorder characterized by the presence of chronic hyperglycemia. DPP-4 inhibitors are a class of oral hypoglycemics commonly used for the treatment of DM. DPP-4 inhibitors block the action of the DPP-4 enzyme, which destroys the hormone incretin. Incretin in turn helps to maintain the desired insulin levels. Our client wanted to develop a systematic literature review on the clinical effectiveness of DPP4 inhibitors in DM management. We screened approximately 3467 studies for 1st pass, 438 studies for second pass and abstracted data from 86 studies. We provided the information to the client in a comprehensive format as a shell report.

Age-related macular degeneration (AMD) is an acquired degeneration of the retina that causes significant central visual impairment through a combination of non-neovascular and neovascular derangement. AMD is a disease of over 45 years of age and prevalence increases with age. Apart from risk factor modification and nutritional supplementation, intravitreal injections of anti-VEGF agents or laser therapy are also used for the treatment of AMD. A client wanted to determine the prevalence and available treatment regimens for AMD. We assisted with 1st pass screening of approximately 2865 studies, 2nd pass screening of 287 studies and subsequent data extraction from 47 studies. The data was used by the client to develop a systematic literature review.

Endstage kidney or renal disease (ESRD) is the last stage of chronic kidney disease leading to permanent kidney damage. Diabetic or hypertensive individuals are at the highest risk of developing ESRD. Specific treatment for renal failure is determined based on the extent of the disease, overall health, and medical history of the patient. Erythropoiesis-stimulating agents are used for the treatment of ESRD as it maintains hemoglobin at the lowest level and minimizes transfusions. Our client wanted to conduct a network meta-analysis to evaluate the global estimate of comparative treatment effectiveness of erythropoiesis-stimulating agents in the management of ESRD. To cater to the client’s objective, we screen approximately 5978 studies for 1st pass, 643 studies for 2nd pass, 12 conference abstracts and finally extracted data from 94 studies. The information was provided to the client in a comprehensive format as a shell report.

Graft-versus-host disease (GVHD) is major complication of allogeneic stem cell transplant used as a treatment for leukemia or lymphoma. GVDH can be life threatening. Our client wanted to develop a systematic literature review on the general attributes of GVDH, focusing primarily on the prevalence and the quality of life of the patients. We extracted relevant information from 110 studies to meet the objective.

Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer accounting for approximately 85% of all lung cancers. Mostly surgery, radiofrequency ablation, radiation therapy, chemotherapy, immunotherapy are used to treat NSCLC. The client wanted to determine the clinical effectiveness of a monoclonal antibody for the immunotherapy (both mono and in combination) of advanced NSCLC. In order to assist our client to develop a systematic review on this topic we screened approximately 1473 studies for 1st pass, 482 studies for 2nd and subsequently extracted data from 194 studies. The review was further updated next year with 1760 1st pass screenings, out of which 185 studies got into 2nd pass phase. Ninety two studies were extracted to update the SLR.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by obstructed airflow from the lungs. There are several recommendations for the management of COPD. Early diagnosis, lifestyle changes and treatment with appropriate medication can slow the progress of this condition. In order to support the global reimbursement of add-on treatment in COPD, a clinical research organization wanted to obtain the relevant economic evidence on COPD. We provided assistance by extracting data on the prior economic models, cost of illness and healthcare resource utilization from approximately 66 studies. The data abstracted was used by the client to generate a systematic literature review on the said topic.

Cytomegalovirus (CMV) is a common virus belonging to the order Herpesvirales and is globally widespread. The unique feature of this virus is that it can remain latent for long period and cause reinfection when the host is immuno-compromised. CMV is a concern for solid organ transplant (SOT) and stem cell transplant (SCT) recipients and can be life threatening. A clinical research organization wanted to develop a systematic literature review on the clinical effectiveness of anti‐CMV agents in the treatment of CMV infected individuals who have undergone solid organ transplantation (SOT) or stem cell transplantation (SCT). We provided assistance by abstracting relevant information from 85 studies.

Chronic kidney disease (CKD) is a condition characterized by gradual loss of kidney function over time. CKD is prevalent among the elderly population and associated with an increased risk of cardiovascular disease and chronic renal failure. It is a global health burden with a high economic cost to health systems. Our client wanted to develop a systematic literature review on the general attributes of CKD, with special focus on the overall quality of life of CKD patients and the cost-effectiveness of the existing treatment modalities. We assisted by abstracting relevant information from 87 studies.

Metastatic breast cancer is unlikely to be cured, but there have been meaningful improvements in survival due to the availability of more effective systemic therapies, including endocrine therapy in the treatment of hormone-sensitive disease. Breast cancer can be further broken down into three subgroups and can be directed according to there treatment choices: 1) the estrogen receptor (ER) expression, 2) the human epidermal growth factor receptor 2 (HER2 [with or without ER expression]), and 3) triple-negative. Patients with ER-positive metastatic breast cancer often respond to endocrine therapy alone or in combination with targeted agents, which can reduce tumour burden and symptoms with generally fewer side effects and toxicities than chemotherapy. Our client wanted to determine the safety and efficacy of existing chemotherapy for breast cancer. In order to assist our client to develop a systematic review on this topic, we screened 1000 studies for the 1st pass and 200 studies for the 2nd pass.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality both in the United States and worldwide. The usual treatments for patients with NSCLC, such as advanced lung adenocarcinoma, are unspecific and aggressive and include lung resection, radiotherapy and chemotherapy. Recently, treatment with monoclonal antibodies and biological inhibitors has emerged as an effective alternative, generating effective results with few side effects. Our client wanted to evaluate efficacy and safety of a monoclonal antibody in combination with radiotherapy in patients with advanced NSCLC. We extracted relevant information from 100 studies to meet the objective.

Rotator cuff tears (RCT) are one of the most frequent shoulder diseases and their incidence increases with advancing age. The tendons of your rotator cuff can tear much like a piece of leather. Sometimes, the tendon is only slightly damaged or irritated. Sometimes, the tendon has a complete tear, which means that the tendon has torn away from the bone. Tears of the rotator cuff tendons may cause shoulder pain and can limit shoulder function. Our client wanted to determine the effectiveness of available treatment on Rotator cuff repair. We extracted relevant information from 40 studies to meet the objective.

MARKET ACCESS AND VALUE STORY DEVELOPMENT

One of our clients wanted to understand the potential to expand access & reimbursement in “Second Tier” markets in India for a mature oncology biologic drug (not immuno-oncology), which is endorsed by international guidelines for 1L use in select cancers. We helped the client in explaining about the level of utilization and reimbursement of biologics in general in the specific markets (not necessarily in oncology), incl. compliance to international guidelines, recent and future landscape changes (including HC policy) that might have an impact on the oncology treatment landscape and specific market access and reimbursement challenges and opportunities relevant for oncology (tendering, level of formularies, budget caps) in India. The findings were shared in the form of a brief report.

Primary liver cancer encompasses Hepatocellular carcinoma (most common primary malignancy of the liver), Cholangiocarcinoma (<10%), and some other rare histologic types. Liver cancer is the 5th most common cancer and the 2nd most frequent cause of cancer-related deaths globally. Current treatment options for HCC are majorly dependent upon the tumor size and include surgical resection, liver transplantation, thermal ablation and chemoembolization. Our client wished to enter this therapeutic domain with an innovative product that uses LTSL (lysolipid thermally sensitive liposome) technology to encapsulate Doxorubicin, a proven and commonly used cancer drug. With the product, that was being evaluated in a global phase 3 clinical trial for the treatment of primary liver cancer, the client wanted to seek further clarity and understanding of the HTA scenario in China – considered to be as one of the most important markets for there product. We helped them by liasoning with China HTA experts and creating HTA landscape assessment report along with oncology specific information. We also provided case studies of products, which got successful market access in China in last decade.

Multiple myeloma is a common hematologic malignancy that has been on rise in Asian countries. Our team aided a pharmaceutical client in generating evidence to demonstrate and support the value of a drug (a selective proteasome inhibitor) for the treatment of multiple myeloma in certain Asian nations. To strengthen the value story, we gathered relevant information through extensive literature search. Approximately 2384 studies were screened for 1st pass, 278 studies were screened for 2nd pass and data was abstracted from 56 studies. Additionally, we developed the value story of the pharmaceutical product of interest based on the data that characterized natural history of disease in the particular Asian locations, burden of illness in those regions, common patterns of care, unmet or under-addressed medical need and benefit-risk profile of the desired pharmaceutical agent

HEOR AND MODELLING PROJECTS

Stigmas associated with HIV in Saudi Arabia have resulted in an increased clinical, humanistic, and economic burden on the country’s healthcare resources. Interventions such as prevention of mother to child transmission (PMTCT) and HIV self-testing (HIVST) might address some of these stigmas and increase diagnosis and treatment of HIV. Client developed a health economic model (Markov model) to estimate the cost-effectiveness of stigma-addressing interventions to improve diagnosis and treatment of HIV from a societal perspective in a KSA setting, using data from various external sources. The stigmas related to having unprotected sex, testing for HIV infection as a member of a risk group, and seeking treatment if infected, were included in the model. It was found out in the research that both PMTCT and HIVST are costing saving stigma-addressing  interventions for PLHIV in KSA. We helped the client in manuscript preparation for the purpose of publication.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is high in the Middle East; however, there are no approved therapies currently available for these conditions. The client developed a health economic model (Markov model) to estimate the current and future clinical, economic and humanistic burden of NAFLD/ NASH in KSA, UAE, and Kuwait, from a societal perspective. Model input data was obtained from population projections from previous studies and UN data. Transition probabilities were calculated after extracting data from similar studies in the past using a graph digitization software. Country-specific costs incurred in the treatment of NAFLD (including medication, medical management, and healthcare procedures) and utility inputs were obtained from local experts. The costs, QALYs and LYs associated with each health state were calculated for all three countries. It was found out that NAFLD/ NASH is associated with substantial clinical, economic, and humanistic burden in the KSA, UAE and Kuwait. We helped the client in creating manuscript from the model report provided to us.

We helped our client to conduct the targeted literature review/secondary literature search to capture information related to Treatment Resistant Depression (TRD) for GCC region (KSA, UAE & Kuwait) and Emerging Markets (Egypt, Algeria, Lebanon & Turkey). We further helped them to build a universal economic model from scratch to assess the over all economic burden (considering direct and indirect cost) of TRD from payers’ and societal perspective and assisted in developing questionnaire for expert interviews to address the gaps identified in the literature search and to populate/validate the model/(s). The model was adapted by populating it with local data specific for each country. The outcome findings were consolidated in the form of white paper and manuscript.

While hospitals remain the most common place of death in many western countries, specialised palliative care (SPC) at home is an alternative option to improve the quality of life in their final days of life. This manuscript is a full economic evaluation (Cost-utility analysis) of an accelerated transition to home for incurable cancer patients in need of palliative care. The analysis is performed from a societal perspective within a randomised controlled trial – the Danish Palliative Care Trial (DOMUS). The researchers looked outcome in the form of incremental cost-effectiveness ratio (ICER) and found out that accelerated specialised palliative care and psychological treatment yields better QALYs than usual care with a large increase in costs. Based on usual willingness-to-pay thresholds, the intervention is not found to be cost-effective relative to usual care. We helped the client in manuscript editing and making it publication ready.

Venous thromboembolism (VTE) is a disease that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). Treatment primarily aims at preventing pulmonary embolism (PE), reduce morbidity, and minimize the risk of post-thrombotic syndrome. So far the mainstay of medical therapy has been anticoagulation. A pharmaceutical company wanted to compare the cost-effectiveness of two anticoagulant drugs used for the treatment and prevention of VTE. The source document and the manuscript outline were provided to us and we assisted our client with drafting the manuscript. The abstract of the manuscript was presented at a conference.

In India, the average cost of cancer treatment ranges from Rs. 2.5 L to Rs. 20 L for six months leading the families into huge economic burden. On the demand of one of our clients,, the information was gathered on the sources of funding for cancer; the services availability in hospitals and clinics; government and non-government schemes for cancer; the process of incentivizing the healthcare providers; the role of drug manufacturer, wholesalers, distributors and providers in drug costing; and reimbursement strategy for cancer treatment in India. It also reports on the complications Indians are facing during cancer treatment.

SYSTEMATIC REVIEWS AND META-ANALYSIS

Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum to the cauda equina which occurs as a result of compulsion, incision or contusion. After spinal cord injury (SCI), the loss of sensory and motor function can lead to secondary urologic complications, such as neurogenic lower urinary tract dysfunction (NLUTD). NLUTD is associated with the risk for several urologic complications including renal failure, bladder cancer, urinary tract infection, incontinence, and morphologic alterations of bladder and urethra. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. The optimal bladder management should prevent secondary complications and ensure patients quality of life. After the traumatic injury the patients usually spends a significant period (depending on country, but sometimes up to 6 – 12 months) in the hospital or rehabilitation unit (institutional period) and are then discharged to live in their own home again or some kind of housing arrangement (community period). Our client wanted to do a thorough literature review to assess the safety (complications like urinary tract infections, stones etc.) of urinary catheters in spinal cord injury patients in rehabilitation phase and community phase from Cochrane and PubMed. Out of initial 1468 initial hits, that we retrieved, as per pre-defined inclusion/exclusion criteria, 48 articles were finally extracted. The detailed findings of the literature review were presented in the form of presentation for internal business decision making of the client.

The role of Calcium Channel Blockers (CCBs) in the reduction of Parkinson’s Disease (PD) has gained increasing attention. The client wanted to examine the protective role of CCBs use in reducing PD. PubMed, EBSCO, and Cochrane library was searched for observational studies on the association between CCBs use and incidence of PD. Based on the selection criteria, out of 626 articles, only six studies (three cohort studies and three case-control studies) involving a total of 27,67,990 subjects including 11,941 cases of PD were selected for the meta-analysis. The random-effects model was used to determine the pooled relative risk (RR) estimates and 95% confidence intervals (CIs). Additionally, subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. Pooled analysis of the observational studies strongly indicated the neuroprotective role of CCBs in significantly reducing the risk of PD.

In patients with primary hyperparathyroidism (PHPT), vitamin D deficiency is a common occurrence that often worsens the patients’ condition. The safety of vitamin D replacement therapy in such patients is not well studied. Our client wanted to evaluate the safety of vitamin D replacement therapy in patients with PHPT. Medline, EMBASE, Cochrane CENTRAL and abstracts form annual scientific meetings of various international bone and mineral societies were searched for relevant information. Out of 310 publications and 90 abstracts identified, only 10 studies enrolling 340 PHPT patients were included in the meta-analysis. The biochemical data was expressed as pooled mean difference (with 95% CI) and sensitivity analysis was conducted after exclusion of studies reporting outlying data. Alongside, the use of random effects model and test for heterogeneity using the I2 statistic, funnel plots were also constructed to determine any publication bias. It was found that vitamin D replacement therapy in mild PHPT with coexistent vitamin D deficiency results in increased 25 (OH) D and significant reduction of parathyroid levels without demonstrating any signs of hypercalcaemia or hypercalciuria.

A particular drug belonging to the janus kinase inhibitor class is approved for the treatment of rheumatoid arthritis (RA). However, there have been increasing concerns regarding the associated adverse effects. Our client was keen on determining the efficacy and safety of the drug for the treatment of RA. PubMed, ClinicalTrials.gov, and Cochrane Library were searched to retrieve relevant information from Phase II and Phase III randomized clinical trials. Based on the inclusion criteria a total of 8 studies (4 studies each of Phase II and Phase III trials) were included in the review. The results revealed the effectiveness of the drug in the management of moderate to severe RA in patients who responded inadequately to methotrexate and tumor necrosis factor inhibitors.

REAL WORLD EVIDENCE/ORIGINAL RESEARCH

Transfusion-transmitted infections (TTIs) are one of the biggest fears to blood transfusion safety. Nucleic acid testing (NAT) in blood donor screening has been implemented in many countries to reduce the risk of TTIs. Our client’s objective of this observational study was to assess the ability of NAT to detect hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) from donor blood samples declared seronegative. Every donor blood sample was screened for HBsAg, anti-HCVnti-HIV-1, anti-HIV-2 and p24 antigen by electrochemiluminescence assay. All initial serology non-reactive samples were subjected to NAT discriminatory assay for HBV, HCV and HIV. It was found out that the routine utilization of MP-NAT testing for HBV, HCV and HIV-1 has the potential to improve the efficacy of screening for protecting blood recipient from TTIs. It enables detection of these viruses, which were undetected by serological test and thus helping in providing safe blood to the patients. We assisted the client in preparing the manuscript for the purpose of publication.

Down’s syndrome is the most common type of chromosomal abnormality found in neonates. It is associated with characteristic abnormal facial features and mental retardation. However, clinical diagnosis is not sufficient to confirm the disease. Classical karyotyping has long been used as diagnostic tool for confirming Down’s syndrome. Our client conducted a study to confirm the cytogenetic composition of individuals suspected with Down’s syndrome after the preliminary clinical diagnosis in Basra, Iraq. We helped the client in manuscript preparation, which is due for publication. Study provided the basic information required to forecast the various complications associated with Down’s syndrome.

Gastric cancer is one of the leading causes of cancer-related deaths across the world and in the Middle East. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression has been observed in gastric cancers. Trastuzumab, a recombinant monoclonal antibody targeting HER2 protein, is now being used for treatment of metastatic gastric cancer. Our client wanted to study the frequency and association of HER2 overexpression with age, gender, histopathological subtype and grade of differentiation in patients with gastric adenocarcinoma. It was a cross-sectional single-centre study. Demographic (age, gender), histopathological (histological subtype, grade of differentiation) and immunohistochemical (HER2 overexpression status) data from 100 consenting adult patients (male: 56) with histopathologically confirmed gastric adenocarcinoma from samples obtained through endoscopy or surgery was collected. We helped the client in preparing the manuscript. It was found that HER2 over-expression was 6% in the population; statistically significant correlation was found with histological grade. Manuscript is still under peer-review.

Co-morbidities are known to have a strong negative association on Overall Survival (OS) of chronic diseases. Charlson Co-morbidity Index (CCI) is one of the known tools to measure the impact of co-morbidities on disease outcomes including leukemias. The researchers aimed to study the effect of co-morbid conditions on the OS among CML patients on tyrosine kinase inhibitors (TKIs) using CCI. It was a retrospective study conducted among patients with CML, treated at Basra Oncology and Hematology Center (Iraq), between year 2006 and 2016. The CCI was calculated using patients’ information taken from hospital records. Patients were divided into two groups – Group 1 (CCI1) included patients with low co-morbidity index of 2 and 3; and Group 2 (CCI2) included patients with high co-morbidity index of 4 and more. Overall survival (OS) probabilities were calculated using Kaplan-Meier curves. It was found out that there was no significant correlation between CCI and OS among CML patients. Diabetes mellitus was the most commonly found co-morbidity among CML patients. We helped the researchers in preparation of manuscript, which is due for publication.

Adequate information about cancer incidence is used to estimate the size of problem, which is crucial for managing and preventing cancer. The client undertook the study to report the incidence and pattern of various types of cancers and their distribution across demographics in Basra, Iraq in the year 2017.  Cancer cases recorded during 2017 at the Basra Cancer Control Centre and Department of Pathology and Forensic Medicine were included in the study along with the cases registered at Basra Oncology and Haematology Centre, Children Basra Hospital and other private laboratories. We analysed the patients’ records including age, gender, region of residence and type of cancer. Percent of incidence for different geographical region was also reported. Distribution of incidence across age groups was reported as percentages. The mean age with standard deviations were reported for patients of different genders and age groups. Incident rate per 100,000 population was calculated for different types of cancer. The findings of the research were put in the form of original manuscript, that has been sent for publication.

Vitamin D deficiency has often been linked to chronic low back pain (CLBP). In many patients, vitamin D deficiency remains undiagnosed therefore untreated leading to persistent, musculoskeletal pain as observed in CLBP. So far no prospective studies have focused on the prevalence of vitamin D deficiency in Indian patients with CLBP. The client wanted to determine the prevalence of vitamin D deficiency in Indian patients and its role in CLBP. Data were obtained from a controlled, open label, single arm clinical trial that assessed the effectiveness of vitamin D supplementation in patients with CLBP. The study was conducted in an outpatient pain clinic of a tertiary care hospital. The findings were reported in accordance with the STROBE (Strengthening the Reporting of Observational studies in Epidemiology) guidelines. Pain and functional disability was determined. Chi-square test and independent t-test was used for the categorical and continuous variables, respectively. Multivariate logistic regression model, univariate analysis of variance (ANOVA) and post hoc Bonferroni test was also used for statistical analysis. The study revealed increased prevalence of vitamin D deficiency among Indian patients with CLBP and indicated the importance of determining the vitamin D status for effective management of CLBP.

Diabetes affects a major proportion of the Indian population. Single anti-diabetic agents are not always effective in controlling this condition. Our client wanted to determine the combined effectiveness of two anti-hyperglycemic agents with complementary mechanisms of action in managing diabetes. An open, prospective, multicenter, single-arm, non-interventional study was conducted across several sites in India. The study was registered under the ClinicalTrials.gov and the Clinical Trial Registry of India. Postprandial glucose, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were measured to determine the clinical effectiveness of the drugs. This study found that the combination of the two anti-hyperglycemic agents was well tolerated, safe and efficacious in Indian patients and could be considered a treatment option for diabetes management.

Hyperglycemia over a prolonged period can damage peripheral nerves and result in increased risk of hand and foot ulcers even resulting in amputations. Such peripheral nerve dysfunction is referred to as diabetic peripheral neuropathy (DPN), a major complication of type 2 diabetes mellitus. While several studies have focused on the prevalence of DPN among the Western population, there is limited data on the prevalence of this condition among the Asian populations, specifically the north Indian population. Our clients not only wanted to assess DPN prevalence in general but also compare the prevalence among populations with established diabetes mellitus and newly detected diabetes mellitus. They also wanted to identify the associated risk factors and possible sex-specific variations. A cross-sectional epidemiological study was conducted at a tertiary care hospital. Student’s t-test, Mann–Whitney U-test or χ2-test, multivariate logistic regression and Kaplan–Meier survival curves were used as a part of the statistical analysis.  The study indicated a high prevalence of DPN among the type 2 diabetes mellitus patients and indicated the importance of early diagnosis and timely screening to prevent DPN progression.

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are a preferred over topical steroids to control inflammation post cataract surgery and a preservative-free variation is considered the most effective. While the clinical effectiveness of the preservative-free NSAID in reducing cystoid macular edema (CME) and macular thickening in patients with cataract surgery is well established across many countries, its safety and efficacy was not studied in Indian patients. The client wanted to evaluate the safety, tolerability and efficacy of the preservative-free NSAID in controlling inflammation in Indian patients who were subjected to cataract surgery. A retrospective, open-labeled, single-arm study was conducted and data was obtained from the records of 96 cataract patients. The results confirmed that the preservative-free NSAID successfully reduced ocular inflammation and was well-tolerated in patients after cataract surgery.

Early Nutritional Support is considered important for ICU management. Previous observational studies have indicated adverse clinical outcomes as a consequence of cumulative calorie debt. Our client hypothesized that early and goal directed enteral nutrition (EN) support to meet the calorie debt could lead to better outcomes. A retrospective observational study was conducted at a multidisciplinary ICU in a tertiary health care facility in India. The data obtained indicated that early initiation and goal directed EN could improve clinical outcome and thus aid in effective ICU management.

Diabetic nephropathy can lead to end stage renal disease (ESRD). Patients with chronic kidney diseases are put on low protein and very low protein diets to improve associated metabolic disorders and uremic symptoms. However, it is important to ensure that the diet fulfills the essential amino acid and energy requirements of the patients.  Our client wanted to determine the efficacy and safety of low protein diet supplemented with keto-analogues of essential amino acids and its superiority over low protein diet without such supplementation. A randomized control trial was conducted at a reputed hospital in Mumbai and a total of 48 patients with diabetic nephropathy were included in this study. The demographic features, post-treatment survival probability etc. were studied. The results suggested the clinical effectiveness of supplemented low protein diet in delaying kidney complications that leads to ESRD. Additionally, the supplemented diet was found to be safe, improve metabolic conditions, and met the nutritional requirement of the patients

Treatment with chimeric mAb often results in the formation of human anti-chimeric antibodies (HACA) that may worsen the condition in axial spondyloarthritis (AS) and rheumatoid arthritis (RA) patients. In this case, our client’s KOL wanted to investigate the effect of infliximab therapy on both AS and RA patients. We did the data analysis and manuscript writing for the client. It was found that HACA was formed in AS patients treated with infliximab, but not in RA patients following same treatment. HACA-positive AS patients treated with chimeric mAb showed a higher post-treatment disease activity as measured by BASDAI and were associated with lesser post-treatment reduction in BASDAI than HACA-negative patients.

CASE SERIES

Autoimmune inner-ear disease (AIED) is a rare autoimmune disorder characterized by progressive hearing loss. Of the several medical therapies proposed for the treatment of AIED, corticosteroid therapy is considered the most effective. Commonly tumor necrosis factor-α inhibitors are administered in combination with corticosteroids for favorable outcomes. The client examined the use of a popular anti-TNF drug in an AIED patient who developed inflammatory polyarthritis (IPA) and was non-responsive to therapy with steroids. The findings confirmed that the anti-TNF agent was successful in managing IPA in the patient with AIED.

Hidradenitis suppurativa (HS), also known as acne inversa, is a rare and long-term skin inflammatory condition diagnosed by small and painful swollen lumps, typically affecting the armpits, the groin, area between the buttocks, and under the breast. The unresponsive routine multiple treatment modalities necessitated a more efficacious treatment for HS. On demand of our clients, the effect of a novel TNF-α inhibitor was studied on two adult patients who were severely affected by HS (Hurley stage III). These two cases were the first of its kind demonstrating the success of this particular TNF-α inhibitor treatment on patients of Indian origin suffering from HS.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a delayed type of systemic hypersensitivity reaction caused by the intake of anti-convulsants, allopurinol, sulfasalazine, NSAIDs and other drugs. It is characterized by maculopapular rashes, fever and eosinophilia affecting the systemic features. This syndrome is severe and fatal than acute drug reaction as it affects internal organs as well. Intake of certain antibiotics, especially the β-lactams such as amoxicillin, may trigger the reaction in the patients of DRESS syndrome. Our client needed a case study for their KOL on a patient who was suffering from DRESS syndrome induced by sulfasalazine and aggravated by ceftriaxone. A prompt withdrawal of sulfasalazine along with intake of systemic corticosteroids and N-acetyl cysteine was found to be useful for a such life-threatening condition.

REVIEWS

Bone turnover markers (BTMs) are key tools in monitoring the effect of anti-resorptive and anabolic therapies against bone pathologies. These tools assist in the management of osteoporosis therapy and predict the associated risks such as, the elevated bone turnover rate could indicate the bone pathologies. International Federation of Clinical Chemistry and International Osteoporosis Foundation have proposed serum C-telopeptide cross-links of type I collagen (CTX-1) and procollagen type 1 amino-terminal propeptide (P1NP) to be used as reference markers for bone resorption and bone formation, respectively. The BTM outcomes could be affected by the uncontrollable factors such as age, gender, pregnancy, menstruation, excess or under mobility, recent fracture, co-morbidities, and medications. We did a thorough literature search to bring the review on the above mentioned topic. We found out that the assessment of BTMs is crucial in elderly patients when adherence with and persistence to the therapy is essential to increase the efficacy of drugs. The advancement of BTMs in clinical and research settings of bone metabolic diseases treated with anti-resorptive and anabolic therapies were described in this review.

India ranks as one of the highest contributors to the global diabetes mellitus (DM) pandemic, with 65 million people i.e. 17% of global 382 million diabetics, residing in India. Diabetes imposes serious threat on overall health status of an individual and can be a risk in itself for multiple chronic and life-threatening diseases such as myocardial infarction, stroke, metabolic syndrome etc. Despite the growing concern regarding DM and its socioeconomic burden, diabetes control in India is far behind what is ideally expected. The mean hemoglobin A1c of diagnosed population is 9.0% – at least 2.0% higher than what is suggested by international bodies. The main objective of this article was to understand the scenario of diabetes in India with respect to its prevalence rate and future disease burden. Our client further aimed to determine the status of diabetes care and management in terms of available facilities, point of care, cost of treatment, various points of intervention and involvement of the non-governmental organizations. They further assessed the awareness level, screening and treatment initiatives for DM within the country with a focus on programs conducted by government bodies and finally reviewed the financial aspect in terms of source of funding and proportion of patients who can afford the treatment. We helped in creating this very interesting white paper for the purpose of publication, out of the information provided to us in the form of power point presentation.

Vitamin D deficiency is a common occurrence and has been linked to several medical conditions including rickets in children to osteoporosis in adults. It also contributes to diabetes, metabolic disorders and cardiovascular disease. Our client wanted to review the pathophysiology of vitamin D deficiency and the associated clinical complications. A detailed review indicated the requirement for novel guidelines on Vitamin D supplementation to achieve better treatment outcomes, improve morbidity and patient health.

Toxic reactive oxygen species (ROS), such as hydrogen peroxide, organic hydro peroxides, nitric oxide, superoxide and hydroxyl radicals etc. are constantly produced under physiological conditions and results in oxidative stress. The resultant imbalance in pro-oxidant/antioxidant homeostasis is responsible for the pathogenesis of different diseases. Our client wanted to obtain clinical evidence from global studies on the critical role of ROS in deteriorating human health and the importance of superoxide dismutase (SOD) in ameliorating the ROS toxicity. Electronic databases (Medline, Pubmed) were searched to identify relevant studies (peer reviewed case studies, observational studies, case control and cohort studies). Extensive data suggested the major role of ROS in the causation of several diseases. It also indicated that in order to maintain defense against ROS, SOD as an exogenous source would be necessary for anti-oxidative defenses.

Diabetic individuals are at increased risk of peripheral arterial disease and neuropathy. Long-term diabetes can cause nerve damage and poor blood flow leading to diabetic foot (DF). It is a major complication that increases the risk of infection, gangrene and amputation in affected individuals. Our client wanted to review the recent advances and evidences that could improve DF management. Medline and Pubmed were searched for relevant information (peer reviewed case studies, observational studies, case control and cohort studies) on DF as a major complication of diabetes. Data obtained indicated major gaps in novel approaches for DF prevention. It was concluded that appropriate awareness regarding diabetes related foot complications, importance of footwear and  regular checkups can help to reduce diabetes related DF.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age. Our client wanted to summarize the underlying causes and common symptoms of PCOS and suggest suitable guidelines for effective management. It was evident that successful treatment of PCOS required proper diagnosis. Therapy mostly depended on the symptoms, age and future pregnancy plans. It was concluded that with accurate diagnosis, appropriate lifestyle interventions, and suitable PCOS treatment (birth control pills to regulate menstruation and insulin-sensitizing or androgen-blocking medications), this medical condition and the associated overwhelming health problems can be controlled.

Telangiectatic osteosarcoma (TO) is an uncommon variant of an intramedullary high grade osteosarcoma that accounts for 2.5-12% of all osteosarcomas. There is limited understanding regarding the incidence, clinical presentation, treatment, and prognosis of this medical condition. The client wanted to systematically study the available literature to obtain detailed information on this high grade osteosarcoma. Literature review revealed poor prognosis of TO patients in earlier studies, however, recent use of neoadjuvant chemotherapy with surgery was reported to improve survival rates of the patients. The finding of this study corroborates the importance of early diagnosis and optimal treatment for improved outcomes.

The hypoglycemic efficacy of dipeptidyl peptidase-4 inhibitor has been demonstrated as monotherapy or in combination of other anti-hyperglycemic drugs. The SAVOR-TIMI 53 trial have raised the concerns about the increased risk of hospitalization due to heart failure following this particular dipeptidyl peptidase-4 inhibitor administration. As per the demand of our clients, all the relevant research articles along with reviews and other data was systematically reviewed.  This systematic study showed that increase in hospitalizations due to heart failure have not been demonstrated by other trials as well as by real-world data analyses from insurance claims data involving a huge number of patients. The vast available evidences favour the clinical usage and safety of this dipeptidyl peptidase-4 inhibitor in various clinical conditions.

Biosimilar is a biologic drug that is structurally and functionally similar to an original drug molecule of biological origin that has already been authorized for use. Generation of evidences for comparing a biosimilar with original biomolecule using direct head-to-head randomized controlled trials can be expensive, time-consuming and laborious. The client wanted a review about the indirect treatment comparison (ITC) for biosimilar that would provide useful evidence for judiciously selecting the best choice of treatment. A well-designed and appropriately conducted ITCs, being increasingly used for biosimilar approval in the EU, can be a valid alternative and means for efficacy and safety evidence generation.

PHYSICIAN'S PERCEPTION MAPPING AND CLINICAL PRACTICE GUIDELINES

Diabetes is a serious health burden and is on the rise across the world. India is no exception with a large population being affected with this condition and newer therapeutic regimes are required for better control. Our client wanted to conduct a survey to understand the view of Indian physicians and endocrinologists regarding the available therapeutic considerations for type 2 diabetes treatment. A questionnaire focusing on issues pertaining to lifestyle intervention prior to initiation of medication was distributed among the physicians working at several primary secondary and tertiary care centers across India. Based on the data from the questionnaires, it was concluded that for newly diagnosed type 2 diabetes, lifestyle intervention was most preferred before pharmacological therapy. Additionally, most physicians preferred metformin as the OHA of initial choice. Drugs of second choice included one of the α-glucosidase inhibitors and DPP4 inhibitor, which were preferred over sulfonylureas.

Combined Hormonal Contraceptives (CHCs) belongs to a group of hormonal contraceptives. CHCs have been successfully used to reduce undesired pregnancies. With this clinical guideline the client wanted to promote awareness among Indian doctors regarding contraception methods and provide an update on the effectiveness and safety of CHC. We obtained clinical evidence from global studies, which was subsequently reviewed by the FOGSI expert committee before finalization of the guidelines. The final guideline addressed issues such as: 1) the unmet need for CHCs, 2) their usage (as contraceptive as well as non-contraceptive), 3) associated side effects, and 4) the importance of structured patient counseling. The guidelines also stressed on the CHC-associated safety concerns including contraception in special situations and provided information on patient counseling tips as well as ways to tailor CHC usage as per the patients’ need.

This guideline was considered the FOGSI Position Statement on the use of Progestogens. Combined Hormonal Contraceptives: Counselling and Use in Clinical Practice.

Venous thromboembolism (VTE) is a global health concern with substantial morbidity and mortality. It is often asymptomatic and under-diagnosed, leading to long-term complications and reduced survival.  VTE has also been identified as an immediate threat to patients undergoing major orthopedic procedures such as total hip arthroplasty (THA) and total knee arthroplasty (TKA). National Orthopedic Advisory Committee meeting was conducted to gain understanding of the clinical relevance of the International VTE prevention guidelines for orthopedic patients in India and to derive expert consensus to enhance optimal implementation of thromboprophylaxis after major orthopedic surgery for Indian population. We helped the client to have guided discussion for better VTE prevention after TKR and THR in Indian patients such as: 1) Thromboprophylactic agents, 2) Minimal duration of thromboprophylaxis, 3) Anticoagulation protocol with neuraxial anesthesia and indwelling epidural catheters, and 4) Bleeding management guidance. The guideline also focused on expert opinion on VTE prevention in patients with renal impairment, bilateral TKR / Revision surgery, mobilization and patient convenience, tolerability and adherence to therapy.

This particular anti-TNF-α factor, is considered effective not only in improving clinical symptoms of psoriasis but also in terms of quality of life. Our client wanted the current evidence from the systematic reviews, post-hoc analyses, registries and real-world data that would represent the associated benefit-risk of this anti-TNF-α factor and other biologics such as anti-T cell agents for psoriasis patients. It was found to be cost-effective and efficacious with no increased incidence of adverse events with escalated dosing. The proven post-marketing safety and efficacy phase, and ease of administration over infliximab are the additional benefits of  the molecule.